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Trial record 47 of 53 for:    "Cryptococcosis"

High-Dose Fluconazole for the Treatment of Cryptococcal Meningitis in HIV-Infected Individuals

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00885703
Recruitment Status : Completed
First Posted : April 22, 2009
Results First Posted : March 12, 2018
Last Update Posted : March 12, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Cryptococcal Meningitis
HIV Infections
Interventions Drug: Fluconazole
Drug: Amphotericin B
Enrollment 168

Recruitment Details The study opened on February 19, 2010. The first participant enrolled on April 16, 2010. Stage 1 closed on September 5, 2013. A5225 Stage 2 opened on September 15, 2014 and the first participant enrolled on February 2, 2015. Stage 2 closed on August 19, 2016. Ten sites enrolled participants (1 domestic, 9 international).
Pre-assignment Details  
Arm/Group Title Stage 1, Fluconazole 1200mg Stage 1, Fluconazole 1600mg Stage 1, Fluconazole 2000mg Stage 1, Ampho B Stage 2, Fluconazole 1600mg Stage 2, Fulconazole 2000mg Stage 2, Ampho B
Hide Arm/Group Description

Participants receive Fluconazole 1200mg induction dose in Stage 1

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 1600mg induction dose in Stage 1

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose in Stage 1

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole in Stage 1

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight

Participants receive Fluconazole 1600mg induction dose in Stage 2

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose in Stage 2

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole in Stage 2

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight

Period Title: Overall Study
Started 22 26 24 24 24 24 24
Completed 12 16 13 15 12 11 18
Not Completed 10 10 11 9 12 13 6
Reason Not Completed
Death             9             7             8             7             7             8             4
Lost to Follow-up             0             0             1             0             0             1             0
Withdrawal by Subject             0             0             0             1             3             1             1
Ineligible (no CM)             1             3             2             1             2             3             1
Arm/Group Title Stage 1, Fluconazole 1200mg Stage 1, Fluconazole 1600mg Stage 1, Fluconazole 2000mg Stage 1, Ampho B Stage 2, Fluconazole 1600mg Stage 2, Fluconazole 2000mg Stage 2, Ampho B Total
Hide Arm/Group Description

Participants receive Fluconazole 1200mg induction dose in Stage 1

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 1600mg induction dose in Stage 1

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose in Stage 1

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole in Stage 1

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight

Participants receive Fluconazole 1600mg induction dose in Stage 2

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose in Stage 2

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole in Stage 2

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight

Total of all reporting groups
Overall Number of Baseline Participants 22 26 24 24 24 24 24 168
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
40.5
(36 to 47)
33
(28 to 39)
38
(31 to 48)
35.5
(30 to 41)
32.5
(29.5 to 35.5)
33.5
(29 to 38)
37.5
(34 to 40)
36
(30 to 41)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
Female
10
  45.5%
14
  53.8%
14
  58.3%
11
  45.8%
10
  41.7%
10
  41.7%
9
  37.5%
78
  46.4%
Male
12
  54.5%
12
  46.2%
10
  41.7%
13
  54.2%
14
  58.3%
14
  58.3%
15
  62.5%
90
  53.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Black Non-Hispanic Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
12
  54.5%
21
  80.8%
22
  91.7%
19
  79.2%
24
 100.0%
22
  91.7%
23
  95.8%
143
  85.1%
Hispanic (regardless of Race) Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
0
   0.0%
4
  15.4%
2
   8.3%
1
   4.2%
0
   0.0%
2
   8.3%
1
   4.2%
10
   6.0%
Asian, Pacific Islander Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
10
  45.5%
1
   3.8%
0
   0.0%
4
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
15
   8.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
1 0 2 1 0 0 0 4
South Africa Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
1 6 3 5 2 3 6 26
Uganda Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
0 2 11 5 14 13 12 57
Zimbabwe Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
2 4 1 3 4 1 3 18
Kenya Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
8 9 7 6 4 6 2 42
Thailand Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
5 0 0 1 0 0 0 6
Peru Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
0 4 0 0 0 1 1 6
India Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
5 1 0 3 0 0 0 9
Weight  
Median (Inter-Quartile Range)
Unit of measure:  Kilograms
Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
46.5
(42.0 to 52.2)
50.5
(44.0 to 65.0)
51.9
(43.5 to 58.5)
56.8
(47.5 to 64.1)
49.8
(44.5 to 60.0)
55.0
(51.6 to 59.1)
52.5
(48.5 to 60.1)
52.0
(44.7 to 59.3)
BMI (Body Mass Index)  
Median (Inter-Quartile Range)
Unit of measure:  Kg/m^2
Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
17.2
(15.6 to 19.6)
19.6
(17.3 to 21.8)
18.3
(17.2 to 22.7)
19.8
(16.3 to 24.3)
18.7
(17.1 to 20.3)
19.8
(18.6 to 22.5)
19.6
(17.5 to 22.9)
18.9
(16.9 to 21.9)
CD4+  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
< 50 cells/mm^3
15
  68.2%
10
  38.5%
17
  70.8%
17
  70.8%
20
  83.3%
16
  66.7%
17
  70.8%
112
  66.7%
50 - <100 cells/mm^3
6
  27.3%
9
  34.6%
4
  16.7%
4
  16.7%
3
  12.5%
5
  20.8%
5
  20.8%
36
  21.4%
100 - <200 cells/mm^3
1
   4.5%
4
  15.4%
3
  12.5%
2
   8.3%
0
   0.0%
3
  12.5%
2
   8.3%
15
   8.9%
200+ cells/mm^3
0
   0.0%
3
  11.5%
0
   0.0%
1
   4.2%
1
   4.2%
0
   0.0%
0
   0.0%
5
   3.0%
HIV-1 RNA  
Median (Inter-Quartile Range)
Unit of measure:  log10(copies/mL)
Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
5.3
(5.1 to 6.0)
5.6
(5.1 to 5.8)
5.5
(5.2 to 5.9)
5.4
(5.2 to 5.7)
5.2
(4.9 to 5.5)
4.9
(2.8 to 5.4)
4.6
(3.5 to 5.5)
5.3
(4.7 to 5.7)
Glasgow Coma Score   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 23 participants 24 participants 167 participants
GCS <15
5
  22.7%
3
  11.5%
5
  20.8%
1
   4.2%
2
   8.3%
0
   0.0%
0
   0.0%
16
   9.6%
GCS =15
17
  77.3%
23
  88.5%
19
  79.2%
23
  95.8%
22
  91.7%
23
 100.0%
24
 100.0%
151
  90.4%
[1]
Measure Description: The Glasgow Coma Score provides an assessment of impairment of conscious level in response to defined stimuli. The GCS is on a scale from 0=worst to 15=best.
[2]
Measure Analysis Population Description: One participant missing baseline Glasgow Coma Score.
Quantitative Cryptococcal Meningitis Culture  
Median (Inter-Quartile Range)
Unit of measure:  Log10 CFU/mL
Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
5.18
(4.23 to 6.02)
4.45
(3.98 to 5.09)
5.15
(4.25 to 5.80)
4.37
(3.33 to 5.23)
5.34
(4.31 to 5.47)
4.29
(2.05 to 5.32)
5.14
(3.40 to 5.42)
5.04
(3.80 to 5.42)
Anti-Retroviral Therapy (ART) Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
On ART
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
8
  33.3%
12
  50.0%
11
  45.8%
31
  18.5%
Not on ART
22
 100.0%
26
 100.0%
24
 100.0%
24
 100.0%
16
  66.7%
12
  50.0%
13
  54.2%
137
  81.5%
Opportunistic Infections  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
One or more opportunistic infections
10
  45.5%
7
  26.9%
11
  45.8%
10
  41.7%
11
  45.8%
9
  37.5%
10
  41.7%
68
  40.5%
No opportunistic infections
12
  54.5%
19
  73.1%
13
  54.2%
14
  58.3%
13
  54.2%
15
  62.5%
14
  58.3%
100
  59.5%
Mini Mental Status   [1] [2] 
Median (Inter-Quartile Range)
Unit of measure:  Scores on a scale
Number Analyzed 19 participants 25 participants 21 participants 22 participants 23 participants 24 participants 24 participants 158 participants
26
(23 to 26)
25
(23 to 26)
26
(22 to 26)
26
(24 to 26)
26
(21 to 26)
26
(19 to 26)
25.5
(20 to 26)
26
(22 to 26)
[1]
Measure Description: The Mini Mental Status is a 26-point questionnaire that is used to measure cognitive impairment. Scale is 0=worst to 26=best.
[2]
Measure Analysis Population Description: Not all participants were able to complete a Mini Mental Status at baseline.
Opening Pressure (from Lumbar Pucture)   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Mm H20
Number Analyzed 21 participants 26 participants 23 participants 23 participants 24 participants 24 participants 24 participants 165 participants
200
(105 to 300)
200
(150 to 290)
350
(180 to 550)
190
(120 to 300)
200
(150 to 254)
190
(120 to 235)
303
(250 to 485)
210
(141 to 320)
[1]
Measure Analysis Population Description: Not all participants were able to have a lumbar puncture at entry.
White Blood Cell count (from CSF)   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Cells/mm^3
Number Analyzed 19 participants 21 participants 23 participants 21 participants 23 participants 23 participants 23 participants 153 participants
80
(30 to 500)
30
(4 to 100)
17
(9 to 310)
26
(15 to 133)
19
(8 to 33)
16
(12 to 89)
13
(8 to 53)
19
(9 to 100)
[1]
Measure Analysis Population Description: Not all participants were able to have a lumbar puncture. Of those that did, not all were able to have enough fluid collected for WBC count.
Albumin   [1] 
Median (Inter-Quartile Range)
Unit of measure:  g/dL
Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 23 participants 24 participants 167 participants
3.0
(2.6 to 3.3)
3.2
(3.1 to 3.6)
3.3
(2.9 to 3.6)
3.2
(2.8 to 3.6)
3.1
(2.8 to 3.2)
3.1
(2.7 to 3.6)
3.1
(2.7 to 3.6)
3.2
(2.8 to 3.5)
[1]
Measure Analysis Population Description: Not all participants had an albumin measurement.
ALT (Alanine Aminotransferase)  
Median (Inter-Quartile Range)
Unit of measure:  U/L
Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
15.7
(11.0 to 22.8)
19.0
(13.0 to 29.2)
24.7
(14.0 to 41.8)
21.5
(11.7 to 32.7)
25.2
(17.4 to 38.0)
24.1
(14.5 to 32.1)
18.1
(14.5 to 35.3)
20.6
(14.0 to 32.6)
Creatinine Clearance  
Mean (Inter-Quartile Range)
Unit of measure:  mL/min
Number Analyzed 22 participants 26 participants 24 participants 24 participants 24 participants 24 participants 24 participants 168 participants
94.2
(79.5 to 112.1)
94.5
(79.3 to 106.3)
94.2
(72.7 to 115.2)
102.3
(81.9 to 135.5)
94.0
(68.2 to 104.0)
98.8
(67.3 to 121.8)
94.4
(77.6 to 113.5)
95.0
(75.0 to 113.3)
Cryptococcal Antigen (CrAG) Titer   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Titers
Number Analyzed 22 participants 23 participants 22 participants 23 participants 23 participants 23 participants 22 participants 158 participants
756
(256 to 8192)
128
(32 to 1024)
815.5
(125 to 8192)
1050
(160 to 4096)
256
(20 to 1024)
128
(16 to 2048)
416
(128 to 4096)
452.5
(32 to 2405)
[1]
Measure Analysis Population Description: Not all participants had a CrAG titer observed at baseline.
1.Primary Outcome
Title Number of Participants Who Discontinued Study-provided High Dose Fluconazole or Ampho B
Hide Description

Discontinuation of study-provided high dose fluconazole at or by week 10 Discontinuation of study-provided ampho B at or by week 2

Discontinuation includes discontinuing for any reason, including progression of symptoms, death, etc.

Time Frame Measured from study entry through Week10
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis in safety population (see study detailed description for details)
Arm/Group Title Stage 1, Fluconazole 1200mg Stage 1, Fluconazole 1600mg Stage 1, Fluconazole 2000mg Stage 1, Ampho B Stage 2, Fluconazole 1600mg Stage 2, Fluconazole 2000mg Stage 2, Ampho B
Hide Arm/Group Description:

Participants receive Fluconazole 1200mg induction dose in Stage 1

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 1600mg induction dose in Stage 1

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose in Stage 1

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole in Stage 1

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight

Participants receive Fluconazole 1600mg induction dose in Stage 2

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose in Stage 2

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole in Stage 2

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight

Overall Number of Participants Analyzed 22 26 24 24 24 24 24
Measure Type: Count of Participants
Unit of Measure: Participants
14
  63.6%
11
  42.3%
11
  45.8%
6
  25.0%
12
  50.0%
13
  54.2%
6
  25.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Stage 1, Fluconazole 1200mg, Stage 1, Fluconazole 1600mg, Stage 1, Fluconazole 2000mg, Stage 1, Ampho B, Stage 2, Fluconazole 1600mg, Stage 2, Fluconazole 2000mg, Stage 2, Ampho B
Comments Testing discontinuation of any dose Fluconazole (pooled by treatment and dose) versus discontinuation of Ampho B (pooled). The null hypothesis is the two treatments have the same proportion of discontinuation.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments Analysis did not adjust for multiple comparisons.
Method Chi-squared
Comments [Not Specified]
2.Primary Outcome
Title Categorized Quantitative Culture Results
Hide Description Count of participants who were CM negative (had no cryptococcal growth), CM negative after switching treatment (switched from Fluconazole to Ampho B or vice versa and later became CM negative), CM positive, Died, Lost to follow-up. Note: CM positive means continued to have cryptococcal growth.
Time Frame At entry, Week 2, and Week 10
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Arms pooled by dose. Analysis in efficacy population (see study detailed description for details).
Arm/Group Title Fluconazole 1200mg Fluconazole 1600mg Fluconazole 2000mg Ampho B
Hide Arm/Group Description:

Participants receive Fluconazole 1200mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 1600mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight

Overall Number of Participants Analyzed 20 45 43 46
Measure Type: Count of Participants
Unit of Measure: Participants
Week 0 CM Positive
20
 100.0%
45
 100.0%
43
 100.0%
46
 100.0%
CM Negative
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
CM Negative after switching treatment
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Died
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Lost to Follow-up
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Week 2 CM Positive
12
  60.0%
27
  60.0%
27
  62.8%
29
  63.0%
CM Negative
3
  15.0%
12
  26.7%
10
  23.3%
13
  28.3%
CM Negative after switching treatment
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Died
5
  25.0%
6
  13.3%
6
  14.0%
4
   8.7%
Lost to Follow-up
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Week 10 CM Positive
3
  15.0%
4
   8.9%
3
   7.0%
2
   4.3%
CM Negative
8
  40.0%
24
  53.3%
22
  51.2%
37
  80.4%
CM Negative after switching treatment
1
   5.0%
4
   8.9%
5
  11.6%
1
   2.2%
Died
8
  40.0%
10
  22.2%
12
  27.9%
5
  10.9%
Lost to Follow-up
0
   0.0%
3
   6.7%
1
   2.3%
1
   2.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluconazole 1200mg, Fluconazole 1600mg, Fluconazole 2000mg, Ampho B
Comments Among 4 treatment arms, comparison of three categorical groups: (CM negative, CM negative after switching treatment, and CM Positive/Died/Lost to Follow-up) at week 10. The null hypothesis is the 4 treatment arms have no differences at week 10.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Primary Outcome
Title Change in Log10 Quantitative CSF Culture Results
Hide Description

Change in quantitative CSF (cerebrospinal fluid) cultures.

Note: No further CSF specimens are drawn following a negative culture. Thus, only week 2 CSF cultures are considered in this analysis.

Time Frame Entry and Week 2
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Arms pooled by dose. Analysis done in efficacy population (see study detailed description for details). Excludes participants who did not have a week 2 observation.
Arm/Group Title Fluconazole 1200mg Fluconazole 1600mg Fluconazole 2000mg Ampho B
Hide Arm/Group Description:

Participants receive Fluconazole 1200mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 1600mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight

Overall Number of Participants Analyzed 15 36 37 40
Median (Inter-Quartile Range)
Unit of Measure: Log10 CFU/mL
-1.51
(-2.90 to -0.91)
-2.51
(-4.00 to -1.44)
-1.78
(-3.24 to -1.00)
-2.81
(-4.09 to -1.92)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluconazole 1200mg, Fluconazole 1600mg, Fluconazole 2000mg, Ampho B
Comments Comparison of change in quantitative CSF culture among 4 treatment arms. The null hypothesis is the 4 treatment arms have the same change in CSF culture from entry to week 2.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments [Not Specified]
Method Kruskal-Wallis
Comments [Not Specified]
4.Primary Outcome
Title Kaplan Meier (KM) Proportion of Participant Mortality
Hide Description Kaplan Meier Proportion of participants who died over study with 90% Confidence Intervals.
Time Frame Measured from study entry through Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Arms pooled by dose in the safety population (see study detailed description for details).
Arm/Group Title Fluconazole 1200mg Fluconazole 1600mg Fluconazole 2000mg Ampho B
Hide Arm/Group Description:

Participants receive Fluconazole 1200mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 1600mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight

Overall Number of Participants Analyzed 22 50 48 48
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: proportion of participants
0.41
(0.26 to 0.60)
0.30
(0.20 to 0.43)
0.36
(0.25 to 0.49)
0.24
(0.15 to 0.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fluconazole 1200mg, Ampho B
Comments Comparison of survival from entry to week 24 between Fluconazole 1200mg arm and Ampho B arm. The null hypothesis is there is no difference in survival between these two arms.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0894
Comments Analysis did not adjust for multiple comparisons.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Fluconazole 1600mg, Ampho B
Comments Comparison of survival from entry to week 24 between Fluconazole 1600mg arm and Ampho B arm. The null hypothesis is there is no difference in survival between these two arms.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4828
Comments Analysis did not adjust for multiple comparisons.
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Fluconazole 2000mg, Ampho B
Comments Comparison of survival from entry to week 24 between Fluconazole 2000mg arm and Ampho B arm. The null hypothesis is there is no difference in survival between these two arms.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1766
Comments Analysis did not adjust for multiple comparisons.
Method Log Rank
Comments [Not Specified]
5.Secondary Outcome
Title Results of the Neurological Examination
Hide Description Results from Glasgow Coma Score, which provides assessment of impairment of conscious level in response to defined stimuli. Min score of 0 and max score of 15 (no mental impairment).
Time Frame Measured at study entry, Week 2, and Week 10
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Arms pooled by dose. Safety population (see study detailed description for details).
Arm/Group Title Fluconazole 1200mg Fluconazole 1600mg Fluconazole 2000mg Ampho B
Hide Arm/Group Description:

Participants receive Fluconazole 1200mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 1600mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight

Overall Number of Participants Analyzed 22 50 48 48
Measure Type: Count of Participants
Unit of Measure: Participants
Week 0 Number Analyzed 22 participants 50 participants 47 participants 48 participants
Score < 15
5
  22.7%
5
  10.0%
5
  10.6%
1
   2.1%
Score = 15
17
  77.3%
45
  90.0%
42
  89.4%
47
  97.9%
Week 2 Number Analyzed 17 participants 42 participants 40 participants 43 participants
Score < 15
2
  11.8%
4
   9.5%
4
  10.0%
5
  11.6%
Score = 15
15
  88.2%
38
  90.5%
36
  90.0%
38
  88.4%
Week 10 Number Analyzed 12 participants 34 participants 27 participants 34 participants
Score < 15
1
   8.3%
1
   2.9%
1
   3.7%
0
   0.0%
Score = 15
11
  91.7%
33
  97.1%
26
  96.3%
34
 100.0%
6.Secondary Outcome
Title Results of Functional Status Evaluation
Hide Description

Functional assessment of work status and ability. Consists of 2 measures: 1) Does participants have full time work status 2) Does participant have functional ability to work.

The measure from 6 week before enrollment will be referred to as 'baseline'.

Time Frame Measured 6 weeks before enrollment, at study entry, at Week 10, and at Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Arms pooled by dose. Safety population (see study detailed description for details).
Arm/Group Title Fluconazole 1200mg Fluconazole 1600mg Fluconazole 2000mg Ampho B
Hide Arm/Group Description:

Participants receive Fluconazole 1200mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 1600mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight

Overall Number of Participants Analyzed 22 50 48 48
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline Had full time work status Number Analyzed 21 participants 50 participants 48 participants 48 participants
18
  85.7%
41
  82.0%
36
  75.0%
42
  87.5%
Entry Had full time work status Number Analyzed 21 participants 50 participants 48 participants 48 participants
3
  14.3%
9
  18.0%
8
  16.7%
9
  18.8%
Week 10 Had full time work status Number Analyzed 12 participants 32 participants 27 participants 34 participants
3
  25.0%
16
  50.0%
9
  33.3%
13
  38.2%
Week 24 Had full time work status Number Analyzed 12 participants 30 participants 23 participants 33 participants
7
  58.3%
18
  60.0%
17
  73.9%
22
  66.7%
Baseline Had functional ability to work Number Analyzed 21 participants 50 participants 48 participants 48 participants
16
  76.2%
41
  82.0%
32
  66.7%
38
  79.2%
Entry Had functional ability to work Number Analyzed 21 participants 50 participants 48 participants 48 participants
1
   4.8%
8
  16.0%
3
   6.3%
7
  14.6%
Week 10 Had functional ability to work Number Analyzed 12 participants 32 participants 27 participants 34 participants
4
  33.3%
18
  56.3%
9
  33.3%
15
  44.1%
Week 24 Had functional ability to work Number Analyzed 12 participants 30 participants 23 participants 33 participants
7
  58.3%
19
  63.3%
16
  69.6%
24
  72.7%
7.Secondary Outcome
Title Length of Hospitalization
Hide Description Duration of first hospitalization in days starting at entry in safety population.
Time Frame Measured from study entry through Week 10
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Arms pooled by dose in safety population (see study detailed description for details). Fluconazole 2000mg arm had one participant data missing (was not admitted to hospital at study entry).
Arm/Group Title Fluconazole 1200mg Fluconazole 1600mg Fluconazole 2000mg Ampho B
Hide Arm/Group Description:

Participants receive Fluconazole 1200mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 1600mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight

Overall Number of Participants Analyzed 22 50 47 48
Median (Inter-Quartile Range)
Unit of Measure: Days
15
(10 to 21)
17.5
(10 to 28)
18
(13 to 36)
18.5
(17 to 26)
8.Secondary Outcome
Title Number of Hospital Admissions
Hide Description Count of number of times a participant was admitted to the hospital.
Time Frame Measured from study entry through Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Arms pooled by dose in safety population (see study detailed description for details).
Arm/Group Title Fluconazole 1200mg Fluconazole 1600mg Fluconazole 2000mg Ampho B
Hide Arm/Group Description:

Participants receive Fluconazole 1200mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 1600mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight

Overall Number of Participants Analyzed 22 50 48 48
Measure Type: Count of Participants
Unit of Measure: Participants
1 hospital admission
18
  81.8%
39
  78.0%
41
  85.4%
37
  77.1%
2 hospital admissions
1
   4.5%
9
  18.0%
6
  12.5%
10
  20.8%
3 hospital admissions
3
  13.6%
2
   4.0%
1
   2.1%
1
   2.1%
9.Secondary Outcome
Title Number of Participants With Progression of Symptoms
Hide Description

Progression of symptoms is defined as:

  • Died (including early deaths)
  • Discontinued Fluconazole and started ampho B
  • Had a positive cryptococcal culture at week 10
  • Microbiological Failure (i.e., relapse of CM)
  • Complication of CM (e.g., obstructive hydrocephalus or vascular complications such as venous or arterial thrombosis)
  • CM IRIS causing increased inflammation after ART exposure
  • New CNS Ol (e.g., toxoplasmosis, PML, CNS lymphoma)
  • Possibly related to CM but mechanism indeterminate
  • Other defined complication unrelated to CM
Time Frame Measured from study entry through Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Arms pooled by dose. Analysis done in efficacy population (see detailed study description for details).
Arm/Group Title Fluconazole 1200mg Fluconazole 1600mg Fluconazole 2000mg Ampho B
Hide Arm/Group Description:

Participants receive Fluconazole 1200mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 1600mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight

Overall Number of Participants Analyzed 20 45 43 46
Measure Type: Count of Participants
Unit of Measure: Participants
14
  70.0%
21
  46.7%
24
  55.8%
19
  41.3%
10.Secondary Outcome
Title Number of Participants With CNS IRIS
Hide Description Number of participants who were diagnosed with CNS immune reconstitution inflammatory syndrome (IRIS)
Time Frame Measured from study entry through Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Arms pooled by dose in study population (see study detailed description for details).
Arm/Group Title Fluconazole 1200mg Fluconazole 1600mg Fluconazole 2000mg Ampho B
Hide Arm/Group Description:

Participants receive Fluconazole 1200mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 1600mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight

Overall Number of Participants Analyzed 22 50 48 48
Measure Type: Count of Participants
Unit of Measure: Participants
1
   4.5%
0
   0.0%
0
   0.0%
1
   2.1%
11.Secondary Outcome
Title Number of Participants With Grade 3 and 4 Adverse Events
Hide Description

Occurrence of grade 3 (severe) and 4 (life-threatening) sign and symptoms events (as defined by FSTRF Appendix 29)

Occurrence of grade 3 (severe) and 4 (life-threatening) laboratory events (as defined by FSTRF Appendix 76)

See DAIDS AE Grading table V1.0

Time Frame Measured from study entry through Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Arms pooled by dose in safety population (see study detailed description for details).
Arm/Group Title Fluconazole 1200mg Fluconazole 1600mg Fluconazole 2000mg Ampho B
Hide Arm/Group Description:

Participants receive Fluconazole 1200mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 1600mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight

Overall Number of Participants Analyzed 22 50 48 48
Measure Type: Count of Participants
Unit of Measure: Participants
Sign/Symptom Events
16
  72.7%
23
  46.0%
32
  66.7%
24
  50.0%
Laboratory Events
12
  54.5%
27
  54.0%
26
  54.2%
30
  62.5%
Time Frame Adverse event data were collected from study entry until end of study (24 weeks).
Adverse Event Reporting Description

The protocol required reporting of all Grade >= 3 signs/symptoms, all Grade >= 2 laboratory toxicities, all estimated creatinine clearance values, and all signs/symptoms or laboratory toxicities that lead to a change in treatment, regardless of grade, were recorded. All diagnoses were recorded.

The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (http://rsc.tech-res.com/safetyandpharmacovigilance/)

 
Arm/Group Title Stage 1: 1200mg Fluconazole Stage 1: 1600mg Fluconazole Stage 1: 2000mg Fluconazole Stage 1: Ampho B Stage 2: 1600mg Fluconazole Stage 2: 2000mg Fluconazole Stage 2: Ampho B
Hide Arm/Group Description

Participants receive Fluconazole 1200mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 1600mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant’s weight

Participants receive Fluconazole 1600mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Fluconazole 2000mg induction dose

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Participants receive Amphotericin B followed by Fluconazole

Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight).

Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally.

Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally.

Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally.

Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant’s weight

All-Cause Mortality
Stage 1: 1200mg Fluconazole Stage 1: 1600mg Fluconazole Stage 1: 2000mg Fluconazole Stage 1: Ampho B Stage 2: 1600mg Fluconazole Stage 2: 2000mg Fluconazole Stage 2: Ampho B
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/22 (40.91%)   7/26 (26.92%)   8/24 (33.33%)   7/24 (29.17%)   7/24 (29.17%)   8/24 (33.33%)   4/24 (16.67%) 
Show Serious Adverse Events Hide Serious Adverse Events
Stage 1: 1200mg Fluconazole Stage 1: 1600mg Fluconazole Stage 1: 2000mg Fluconazole Stage 1: Ampho B Stage 2: 1600mg Fluconazole Stage 2: 2000mg Fluconazole Stage 2: Ampho B
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/22 (63.64%)   13/26 (50.00%)   13/24 (54.17%)   11/24 (45.83%)   10/24 (41.67%)   12/24 (50.00%)   6/24 (25.00%) 
Blood and lymphatic system disorders               
Anaemia  1  0/22 (0.00%)  0/26 (0.00%)  1/24 (4.17%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Febrile neutropenia  1  0/22 (0.00%)  0/26 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Neutropenia  1  1/22 (4.55%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Cardiac disorders               
Cardio-respiratory arrest  1  0/22 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Gastrointestinal disorders               
Gastritis  1  0/22 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Gastrointestinal haemorrhage  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Peptic ulcer  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
General disorders               
Death  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%) 
Pyrexia  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Immune system disorders               
Immune reconstitution inflammatory syndrome  1  1/22 (4.55%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%) 
Infections and infestations               
Bacteraemia  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Bronchitis  1  0/22 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Cerebral toxoplasmosis  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Disseminated cryptococcosis  1  2/22 (9.09%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%) 
Disseminated tuberculosis  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Malaria  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Meningitis bacterial  1  0/22 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Meningitis cryptococcal  1  5/22 (22.73%)  7/26 (26.92%)  6/24 (25.00%)  2/24 (8.33%)  5/24 (20.83%)  2/24 (8.33%)  4/24 (16.67%) 
Pneumocystis jirovecii pneumonia  1  0/22 (0.00%)  0/26 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Pneumonia  1  1/22 (4.55%)  0/26 (0.00%)  3/24 (12.50%)  0/24 (0.00%)  1/24 (4.17%)  2/24 (8.33%)  0/24 (0.00%) 
Pulmonary tuberculosis  1  0/22 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Sepsis  1  0/22 (0.00%)  1/26 (3.85%)  1/24 (4.17%)  2/24 (8.33%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Septic shock  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%) 
Urinary tract infection  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Injury, poisoning and procedural complications               
Overdose  1  1/22 (4.55%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Subdural haematoma  1  1/22 (4.55%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Toxicity to various agents  1  1/22 (4.55%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Investigations               
Electrocardiogram QT prolonged  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Haemoglobin decreased  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Hepatic enzyme increased  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%) 
Weight decreased  1  0/22 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%) 
Metabolism and nutrition disorders               
Hyponatraemia  1  0/22 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Musculoskeletal and connective tissue disorders               
Muscular weakness  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Diffuse large B-cell lymphoma  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Immune reconstitution inflammatory syndrome associated Kaposi's sarcoma  1  1/22 (4.55%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Kaposi's sarcoma  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%) 
Nervous system disorders               
Encephalopathy  1  1/22 (4.55%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Facial paralysis  1  0/22 (0.00%)  0/26 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Headache  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Hemiparesis  1  1/22 (4.55%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Intracranial pressure increased  1  2/22 (9.09%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Seizure  1  2/22 (9.09%)  2/26 (7.69%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Superior sagittal sinus thrombosis  1  0/22 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Renal and urinary disorders               
Acute kidney injury  1  1/22 (4.55%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Dyspnoea  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%) 
Pneumonia aspiration  1  1/22 (4.55%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Pulmonary embolism  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Skin and subcutaneous tissue disorders               
Photosensitivity reaction  1  1/22 (4.55%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Stevens-Johnson syndrome  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Stage 1: 1200mg Fluconazole Stage 1: 1600mg Fluconazole Stage 1: 2000mg Fluconazole Stage 1: Ampho B Stage 2: 1600mg Fluconazole Stage 2: 2000mg Fluconazole Stage 2: Ampho B
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   22/22 (100.00%)   26/26 (100.00%)   24/24 (100.00%)   24/24 (100.00%)   24/24 (100.00%)   24/24 (100.00%)   24/24 (100.00%) 
Blood and lymphatic system disorders               
Anaemia  1  3/22 (13.64%)  2/26 (7.69%)  0/24 (0.00%)  3/24 (12.50%)  1/24 (4.17%)  3/24 (12.50%)  5/24 (20.83%) 
Lymphadenopathy  1  1/22 (4.55%)  1/26 (3.85%)  2/24 (8.33%)  2/24 (8.33%)  1/24 (4.17%)  1/24 (4.17%)  2/24 (8.33%) 
Neutropenia  1  1/22 (4.55%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  3/24 (12.50%)  0/24 (0.00%)  0/24 (0.00%) 
Cardiac disorders               
Palpitations  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  1/24 (4.17%) 
Tachycardia  1  0/22 (0.00%)  0/26 (0.00%)  3/24 (12.50%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Eye disorders               
Conjunctival hyperaemia  1  2/22 (9.09%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Vision blurred  1  1/22 (4.55%)  0/26 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  1/24 (4.17%) 
Visual impairment  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  2/24 (8.33%) 
Gastrointestinal disorders               
Abdominal pain  1  0/22 (0.00%)  2/26 (7.69%)  1/24 (4.17%)  3/24 (12.50%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%) 
Abdominal pain upper  1  0/22 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  2/24 (8.33%)  1/24 (4.17%)  2/24 (8.33%)  0/24 (0.00%) 
Anorectal swelling  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  0/24 (0.00%) 
Constipation  1  0/22 (0.00%)  0/26 (0.00%)  3/24 (12.50%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%) 
Diarrhoea  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  2/24 (8.33%)  1/24 (4.17%)  3/24 (12.50%)  1/24 (4.17%) 
Gastritis  1  1/22 (4.55%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%) 
Nausea  1  1/22 (4.55%)  2/26 (7.69%)  1/24 (4.17%)  3/24 (12.50%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Odynophagia  1  1/22 (4.55%)  2/26 (7.69%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Oral disorder  1  2/22 (9.09%)  0/26 (0.00%)  1/24 (4.17%)  2/24 (8.33%)  1/24 (4.17%)  1/24 (4.17%)  2/24 (8.33%) 
Stomatitis  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  2/24 (8.33%)  1/24 (4.17%)  0/24 (0.00%) 
Vomiting  1  1/22 (4.55%)  4/26 (15.38%)  4/24 (16.67%)  5/24 (20.83%)  5/24 (20.83%)  6/24 (25.00%)  5/24 (20.83%) 
General disorders               
Asthenia  1  0/22 (0.00%)  0/26 (0.00%)  2/24 (8.33%)  2/24 (8.33%)  1/24 (4.17%)  1/24 (4.17%)  0/24 (0.00%) 
Chest pain  1  3/22 (13.64%)  2/26 (7.69%)  1/24 (4.17%)  2/24 (8.33%)  0/24 (0.00%)  1/24 (4.17%)  1/24 (4.17%) 
Fatigue  1  3/22 (13.64%)  2/26 (7.69%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Malaise  1  0/22 (0.00%)  0/26 (0.00%)  4/24 (16.67%)  2/24 (8.33%)  10/24 (41.67%)  5/24 (20.83%)  5/24 (20.83%) 
Pyrexia  1  7/22 (31.82%)  6/26 (23.08%)  7/24 (29.17%)  8/24 (33.33%)  6/24 (25.00%)  4/24 (16.67%)  3/24 (12.50%) 
Infections and infestations               
Bacteraemia  1  0/22 (0.00%)  0/26 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  2/24 (8.33%)  2/24 (8.33%)  0/24 (0.00%) 
Cerebral toxoplasmosis  1  0/22 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  1/24 (4.17%)  2/24 (8.33%)  1/24 (4.17%)  1/24 (4.17%) 
Encephalitis cytomegalovirus  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  1/24 (4.17%)  3/24 (12.50%) 
Herpes zoster  1  0/22 (0.00%)  2/26 (7.69%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  3/24 (12.50%) 
Malaria  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%) 
Meningitis cryptococcal  1  6/22 (27.27%)  8/26 (30.77%)  9/24 (37.50%)  10/24 (41.67%)  6/24 (25.00%)  8/24 (33.33%)  5/24 (20.83%) 
Meningitis tuberculous  1  1/22 (4.55%)  1/26 (3.85%)  3/24 (12.50%)  2/24 (8.33%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Oral candidiasis  1  0/22 (0.00%)  0/26 (0.00%)  2/24 (8.33%)  3/24 (12.50%)  1/24 (4.17%)  1/24 (4.17%)  2/24 (8.33%) 
Oral herpes  1  2/22 (9.09%)  0/26 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  1/24 (4.17%) 
Pneumocystis jirovecii pneumonia  1  4/22 (18.18%)  0/26 (0.00%)  1/24 (4.17%)  1/24 (4.17%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%) 
Pneumonia  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  0/24 (0.00%) 
Pneumonia bacterial  1  2/22 (9.09%)  1/26 (3.85%)  2/24 (8.33%)  2/24 (8.33%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%) 
Pulmonary tuberculosis  1  1/22 (4.55%)  2/26 (7.69%)  2/24 (8.33%)  2/24 (8.33%)  0/24 (0.00%)  2/24 (8.33%)  1/24 (4.17%) 
Septic shock  1  1/22 (4.55%)  0/26 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  2/24 (8.33%) 
Tuberculosis gastrointestinal  1  0/22 (0.00%)  2/26 (7.69%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Upper respiratory tract infection  1  0/22 (0.00%)  0/26 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  1/24 (4.17%) 
Urinary tract infection  1  0/22 (0.00%)  1/26 (3.85%)  1/24 (4.17%)  3/24 (12.50%)  1/24 (4.17%)  2/24 (8.33%)  0/24 (0.00%) 
Investigations               
Alanine aminotransferase increased  1  4/22 (18.18%)  5/26 (19.23%)  6/24 (25.00%)  3/24 (12.50%)  4/24 (16.67%)  2/24 (8.33%)  2/24 (8.33%) 
Aspartate aminotransferase increased  1  8/22 (36.36%)  5/26 (19.23%)  9/24 (37.50%)  7/24 (29.17%)  6/24 (25.00%)  3/24 (12.50%)  6/24 (25.00%) 
Blood albumin decreased  1  19/22 (86.36%)  18/26 (69.23%)  18/24 (75.00%)  19/24 (79.17%)  19/24 (79.17%)  17/24 (70.83%)  21/24 (87.50%) 
Blood alkaline phosphatase increased  1  4/22 (18.18%)  2/26 (7.69%)  7/24 (29.17%)  1/24 (4.17%)  5/24 (20.83%)  2/24 (8.33%)  5/24 (20.83%) 
Blood bicarbonate decreased  1  4/22 (18.18%)  9/26 (34.62%)  16/24 (66.67%)  6/24 (25.00%)  10/24 (41.67%)  14/24 (58.33%)  10/24 (41.67%) 
Blood bilirubin increased  1  0/22 (0.00%)  0/26 (0.00%)  3/24 (12.50%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%)  2/24 (8.33%) 
Blood calcium decreased  1  2/22 (9.09%)  0/26 (0.00%)  1/24 (4.17%)  1/24 (4.17%)  0/24 (0.00%)  1/24 (4.17%)  1/24 (4.17%) 
Blood creatine phosphokinase increased  1  3/22 (13.64%)  0/26 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Blood creatinine increased  1  5/22 (22.73%)  4/26 (15.38%)  8/24 (33.33%)  12/24 (50.00%)  7/24 (29.17%)  5/24 (20.83%)  13/24 (54.17%) 
Blood glucose decreased  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  1/24 (4.17%)  1/24 (4.17%) 
Blood glucose increased  1  12/22 (54.55%)  7/26 (26.92%)  9/24 (37.50%)  7/24 (29.17%)  6/24 (25.00%)  8/24 (33.33%)  8/24 (33.33%) 
Blood magnesium decreased  1  5/22 (22.73%)  0/26 (0.00%)  4/24 (16.67%)  8/24 (33.33%)  2/24 (8.33%)  3/24 (12.50%)  9/24 (37.50%) 
Blood phosphorus decreased  1  1/22 (4.55%)  0/26 (0.00%)  2/24 (8.33%)  3/24 (12.50%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Blood potassium decreased  1  14/22 (63.64%)  7/26 (26.92%)  10/24 (41.67%)  13/24 (54.17%)  6/24 (25.00%)  9/24 (37.50%)  13/24 (54.17%) 
Blood potassium increased  1  2/22 (9.09%)  0/26 (0.00%)  1/24 (4.17%)  2/24 (8.33%)  0/24 (0.00%)  3/24 (12.50%)  2/24 (8.33%) 
Blood pressure increased  1  1/22 (4.55%)  0/26 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Blood sodium decreased  1  19/22 (86.36%)  21/26 (80.77%)  21/24 (87.50%)  20/24 (83.33%)  18/24 (75.00%)  18/24 (75.00%)  22/24 (91.67%) 
Haemoglobin decreased  1  8/22 (36.36%)  11/26 (42.31%)  9/24 (37.50%)  11/24 (45.83%)  8/24 (33.33%)  8/24 (33.33%)  17/24 (70.83%) 
Neutrophil count decreased  1  4/22 (18.18%)  8/26 (30.77%)  11/24 (45.83%)  6/24 (25.00%)  14/24 (58.33%)  8/24 (33.33%)  10/24 (41.67%) 
Platelet count decreased  1  7/22 (31.82%)  5/26 (19.23%)  7/24 (29.17%)  5/24 (20.83%)  8/24 (33.33%)  5/24 (20.83%)  5/24 (20.83%) 
Weight decreased  1  1/22 (4.55%)  0/26 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  1/24 (4.17%)  4/24 (16.67%)  1/24 (4.17%) 
White blood cell count decreased  1  5/22 (22.73%)  3/26 (11.54%)  6/24 (25.00%)  6/24 (25.00%)  12/24 (50.00%)  6/24 (25.00%)  6/24 (25.00%) 
Metabolism and nutrition disorders               
Abnormal loss of weight  1  3/22 (13.64%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%) 
Cachexia  1  0/22 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  2/24 (8.33%)  3/24 (12.50%) 
Decreased appetite  1  2/22 (9.09%)  3/26 (11.54%)  1/24 (4.17%)  0/24 (0.00%)  4/24 (16.67%)  2/24 (8.33%)  1/24 (4.17%) 
Hypokalaemia  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  1/24 (4.17%)  2/24 (8.33%) 
Musculoskeletal and connective tissue disorders               
Back pain  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  0/24 (0.00%) 
Muscular weakness  1  1/22 (4.55%)  0/26 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  1/24 (4.17%) 
Musculoskeletal stiffness  1  2/22 (9.09%)  2/26 (7.69%)  2/24 (8.33%)  1/24 (4.17%)  2/24 (8.33%)  1/24 (4.17%)  0/24 (0.00%) 
Neck pain  1  1/22 (4.55%)  1/26 (3.85%)  2/24 (8.33%)  2/24 (8.33%)  1/24 (4.17%)  0/24 (0.00%)  0/24 (0.00%) 
Pain in extremity  1  1/22 (4.55%)  1/26 (3.85%)  1/24 (4.17%)  2/24 (8.33%)  2/24 (8.33%)  1/24 (4.17%)  0/24 (0.00%) 
Nervous system disorders               
Altered state of consciousness  1  3/22 (13.64%)  0/26 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Dizziness  1  1/22 (4.55%)  3/26 (11.54%)  1/24 (4.17%)  1/24 (4.17%)  0/24 (0.00%)  1/24 (4.17%)  1/24 (4.17%) 
Headache  1  4/22 (18.18%)  4/26 (15.38%)  8/24 (33.33%)  6/24 (25.00%)  7/24 (29.17%)  5/24 (20.83%)  7/24 (29.17%) 
Seizure  1  2/22 (9.09%)  2/26 (7.69%)  2/24 (8.33%)  4/24 (16.67%)  2/24 (8.33%)  3/24 (12.50%)  2/24 (8.33%) 
Somnolence  1  1/22 (4.55%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%) 
Psychiatric disorders               
Confusional state  1  4/22 (18.18%)  2/26 (7.69%)  4/24 (16.67%)  4/24 (16.67%)  0/24 (0.00%)  3/24 (12.50%)  2/24 (8.33%) 
Depressed mood  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  0/24 (0.00%) 
Renal and urinary disorders               
Dysuria  1  0/22 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  2/24 (8.33%)  1/24 (4.17%)  2/24 (8.33%)  0/24 (0.00%) 
Micturition urgency  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Pollakiuria  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Cough  1  4/22 (18.18%)  4/26 (15.38%)  6/24 (25.00%)  3/24 (12.50%)  3/24 (12.50%)  2/24 (8.33%)  3/24 (12.50%) 
Dyspnoea  1  6/22 (27.27%)  0/26 (0.00%)  4/24 (16.67%)  1/24 (4.17%)  1/24 (4.17%)  3/24 (12.50%)  1/24 (4.17%) 
Rales  1  0/22 (0.00%)  0/26 (0.00%)  1/24 (4.17%)  2/24 (8.33%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%) 
Skin and subcutaneous tissue disorders               
Night sweats  1  0/22 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  2/24 (8.33%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Prurigo  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  1/24 (4.17%)  3/24 (12.50%) 
Pruritus  1  0/22 (0.00%)  1/26 (3.85%)  0/24 (0.00%)  0/24 (0.00%)  2/24 (8.33%)  1/24 (4.17%)  4/24 (16.67%) 
Pruritus generalised  1  1/22 (4.55%)  0/26 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  2/24 (8.33%)  1/24 (4.17%) 
Rash  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  1/24 (4.17%)  2/24 (8.33%) 
Rash papular  1  1/22 (4.55%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%)  3/24 (12.50%) 
Skin discolouration  1  0/22 (0.00%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  3/24 (12.50%) 
Swelling face  1  2/22 (9.09%)  0/26 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  1/24 (4.17%)  0/24 (0.00%) 
Vascular disorders               
Hypertension  1  2/22 (9.09%)  0/26 (0.00%)  1/24 (4.17%)  1/24 (4.17%)  1/24 (4.17%)  1/24 (4.17%)  1/24 (4.17%) 
Hypotension  1  2/22 (9.09%)  1/26 (3.85%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%)  0/24 (0.00%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
Results Point of Contact
Name/Title: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Phone: (301) 628-3313
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00885703     History of Changes
Other Study ID Numbers: A5225 (HiFLAC)
10149 ( Registry Identifier: DAIDS-ES )
ACTG A5225
HiFLAC
A5225/HiFLAC
A5225
First Submitted: April 20, 2009
First Posted: April 22, 2009
Results First Submitted: January 11, 2018
Results First Posted: March 12, 2018
Last Update Posted: March 12, 2018