Amphotericin Alone or in Combination With Fluconazole for AIDS-Associated Meningitis
This study has been completed.
Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00145249
First received: September 2, 2005
Last updated: May 10, 2012
Last verified: October 2009
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Results First Received: March 18, 2010
| Study Type: | Interventional |
|---|---|
| Study Design: | Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment |
| Condition: |
Cryptococcal Meningitis |
| Interventions: |
Drug: Amphotericin B Drug: Fluconazole |
Participant Flow
Hide Participant Flow
Recruitment Details
| Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations |
|---|
| Subjects were screened and enrolled at 10 sites in the US and 5 sites in Thailand. |
Pre-Assignment Details
| Significant events and approaches for the overall study following participant enrollment, but prior to group assignment |
|---|
| No text entered. |
Reporting Groups
| Description | |
|---|---|
| AmphoB Standard | Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed. |
| AmphoB+Fluc400 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks. |
| AmphoB + Fluc800 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks. |
Participant Flow: Overall Study
| AmphoB Standard | AmphoB+Fluc400 | AmphoB + Fluc800 | |
|---|---|---|---|
| STARTED | 47 [1] | 48 [2] | 48 [3] |
| COMPLETED | 36 | 33 | 31 |
| NOT COMPLETED | 11 | 15 | 17 |
| [1] | 47 subjects randomized; 45 subjects treated |
|---|---|
| [2] | 48 subjects randomized; 47 subjects treated-2 subjects randomized to AmphoB rec'd AmphoB+Fluc400 |
| [3] | 48 subjects randomized; 49 treated-3 subjects randomized to AmphoB+Fluc400 rec'd AmphoB+Fluc800 |
Baseline Characteristics
Population Description
| Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
|---|
| No text entered. |
Reporting Groups
| Description | |
|---|---|
| AmphoB Standard | Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed. |
| AmphoB+Fluc400 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks. |
| AmphoB + Fluc800 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks. |
| Total | Total of all reporting groups |
Baseline Measures
| AmphoB Standard | AmphoB+Fluc400 | AmphoB + Fluc800 | Total | |
|---|---|---|---|---|
|
Number of Participants
[units: participants] |
45 | 47 | 49 | 141 |
|
Age
[units: participants] |
||||
| <=18 years | 0 | 0 | 1 | 1 |
| Between 18 and 65 years | 45 | 47 | 47 | 139 |
| >=65 years | 0 | 0 | 1 | 1 |
|
Age
[units: years] Mean (Standard Deviation) |
37.1 (8.47) | 36.5 (8.21) | 35.9 (9.44) | 36.5 (8.69) |
|
Gender
[units: participants] |
||||
| Female | 16 | 15 | 18 | 49 |
| Male | 29 | 32 | 31 | 92 |
|
Region of Enrollment
[units: participants] |
||||
| United States | 14 | 14 | 14 | 42 |
| Thailand | 31 | 33 | 35 | 99 |
Outcome Measures
| 1. Primary: | Number of Grade 3-5 Adverse Experiences That Are Definitely or Probably Related to Study Drug [ Time Frame: Day 100 ] |
| Measure Type | Primary |
|---|---|
| Measure Title | Number of Grade 3-5 Adverse Experiences That Are Definitely or Probably Related to Study Drug |
| Measure Description |
Events are reported by MedDRA Preferred Term. Grade 3 - Severe. Incapacitating; inability to perform usual activities and daily tasks; significantly affects clinical status; requires therapeutic intervention. Grade 4 - Life-threatening. AE is life-threatening. Grade 5 - Death. AE causes death. |
| Time Frame | Day 100 |
| Safety Issue | Yes |
Population Description
| Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
|---|
| The Regulatory Safety population includes all subjects who were randomized, who receive at least 1 dose of study drug, and who have any on-study data. |
Reporting Groups
| Description | |
|---|---|
| AmphoB Standard | Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed. |
| AmphoB+Fluc400 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks. |
| AmphoB + Fluc800 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks. |
Measured Values
| AmphoB Standard | AmphoB+Fluc400 | AmphoB + Fluc800 | |
|---|---|---|---|
|
Number of Participants Analyzed
[units: participants] |
45 | 47 | 49 |
|
Number of Grade 3-5 Adverse Experiences That Are Definitely or Probably Related to Study Drug
[units: Events] |
|||
| Hypomagnesaemia | 2 | 1 | 0 |
| Hypokalaemia | 0 | 0 | 1 |
| Anaemia | 1 | 1 | 0 |
| Drug intolerance | 1 | 0 | 0 |
| Creatinine renal clearance increased | 0 | 0 | 1 |
| Psychotic disorder | 0 | 0 | 1 |
No statistical analysis provided for Number of Grade 3-5 Adverse Experiences That Are Definitely or Probably Related to Study Drug
| 2. Primary: | Number of Dose-limiting Toxicities Attributed to Treatment Regimens [ Time Frame: Day 100 ] |
| Measure Type | Primary |
|---|---|
| Measure Title | Number of Dose-limiting Toxicities Attributed to Treatment Regimens |
| Measure Description |
Events are reported by MedDRA Preferred Term. Dose limiting toxicities include events that resulted in study drug being adjusted, interrupted, or discontinued. |
| Time Frame | Day 100 |
| Safety Issue | Yes |
Population Description
| Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
|---|
| The Regulatory Safety population includes all subjects who were randomized, who receive at least 1 dose of study drug, and who have any on-study data. |
Reporting Groups
| Description | |
|---|---|
| AmphoB Standard | Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed. |
| AmphoB+Fluc400 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks. |
| AmphoB + Fluc800 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks. |
Measured Values
| AmphoB Standard | AmphoB+Fluc400 | AmphoB + Fluc800 | |
|---|---|---|---|
|
Number of Participants Analyzed
[units: participants] |
45 | 47 | 49 |
|
Number of Dose-limiting Toxicities Attributed to Treatment Regimens
[units: Events] |
|||
| All Events | 6 | 7 | 14 |
| Blood creatinine increased | 4 | 1 | 1 |
| Creatinine renal clearance decreased | 0 | 1 | 2 |
| Creatinine renal clearance increased | 0 | 0 | 2 |
| Renal failure | 0 | 2 | 0 |
| Renal failure acute | 0 | 1 | 1 |
| Azotaemia | 0 | 0 | 1 |
| Renal impairment | 0 | 0 | 1 |
| Nausea | 0 | 0 | 1 |
| Vomiting | 0 | 0 | 1 |
| Drug intolerance | 1 | 1 | 0 |
| Chills | 0 | 1 | 0 |
| Neutropenia | 0 | 0 | 1 |
| Hepatitis acute | 1 | 0 | 0 |
| Pneumonia | 0 | 0 | 1 |
| Dehydration | 0 | 0 | 1 |
| Respiratory failure | 0 | 0 | 1 |
No statistical analysis provided for Number of Dose-limiting Toxicities Attributed to Treatment Regimens
| 3. Secondary: | Number of Deaths [ Time Frame: 14, 42, and 70 days ] |
| Measure Type | Secondary |
|---|---|
| Measure Title | Number of Deaths |
| Measure Description |
Number of deaths occurring on study. Day = Day relative to the first dose of study drug. |
| Time Frame | 14, 42, and 70 days |
| Safety Issue | Yes |
Population Description
| Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
|---|
| The Regulatory Safety Population was used in this analysis, which includes all subjects who were randomized, who received at least 1 dose of study drug, and who have any on-study data. |
Reporting Groups
| Description | |
|---|---|
| AmphoB Standard | Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed. |
| AmphoB+Fluc400 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks. |
| AmphoB + Fluc800 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks. |
Measured Values
| AmphoB Standard | AmphoB+Fluc400 | AmphoB + Fluc800 | |
|---|---|---|---|
|
Number of Participants Analyzed
[units: participants] |
45 | 47 | 49 |
|
Number of Deaths
[units: Subjects] |
|||
| All Deaths | 10 | 8 | 9 |
| Day 1-14 | 3 | 2 | 1 |
| Day 15-42 | 3 | 2 | 1 |
| Day 43-70 | 1 | 2 | 5 |
| Day >70 | 3 | 2 | 2 |
No statistical analysis provided for Number of Deaths
| 4. Secondary: | Number of Subjects With Cerebrospinal Fluid (CSF) Culture Conversion at Multiple Time Points [ Time Frame: Baseline, 14, 42, and 70 days ] |
| Measure Type | Secondary |
|---|---|
| Measure Title | Number of Subjects With Cerebrospinal Fluid (CSF) Culture Conversion at Multiple Time Points |
| Measure Description | Number of subjects that have a negative fungal culture at Baseline, Day 14, Day 42, and Day 70. |
| Time Frame | Baseline, 14, 42, and 70 days |
| Safety Issue | No |
Population Description
| Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
|---|
| The modified Intent to Treat (mITT) population includes all subjects who are randomized to a treatment arm and receive any dose of study drug, who provide any outcome data, and who are determined to have met 2 key criteria for inclusion in the primary analysis - diagnosis of culture-proven cryptococcal meningitis and proven HIV infection. |
Reporting Groups
| Description | |
|---|---|
| AmphoB Standard | Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed. |
| AmphoB+Fluc400 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks. |
| AmphoB + Fluc800 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks. |
Measured Values
| AmphoB Standard | AmphoB+Fluc400 | AmphoB + Fluc800 | |
|---|---|---|---|
|
Number of Participants Analyzed
[units: participants] |
46 | 48 | 41 |
|
Number of Subjects With Cerebrospinal Fluid (CSF) Culture Conversion at Multiple Time Points
[units: Subjects] |
|||
| Baseline - Negative | 0 | 0 | 0 |
| Day 14 - Negative | 20 | 13 | 22 |
| Day 42 - Negative | 35 | 37 | 36 |
| Day 70 - Negative | 36 | 39 | 38 |
No statistical analysis provided for Number of Subjects With Cerebrospinal Fluid (CSF) Culture Conversion at Multiple Time Points
| 5. Secondary: | Number of Subjects Meeting the Key Efficacy Endpoint of Treatment Success [ Time Frame: 14, 42, and 70 days ] |
| Measure Type | Secondary |
|---|---|
| Measure Title | Number of Subjects Meeting the Key Efficacy Endpoint of Treatment Success |
| Measure Description | Treatment success is defined as a composite of the 3 mycologic and clinical measures: CSF culture conversion; neurologically stable or improved; and alive |
| Time Frame | 14, 42, and 70 days |
| Safety Issue | No |
Population Description
| Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
|---|
| The mITT population includes all subjects who are randomized to a treatment arm and receive any dose of study drug, who provide any outcome data, and who are determined to have met 2 key criteria for inclusion in the primary analysis - diagnosis of culture-proven cryptococcal meningitis and proven HIV infection. |
Reporting Groups
| Description | |
|---|---|
| AmphoB Standard | Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed. |
| AmphoB+Fluc400 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks. |
| AmphoB + Fluc800 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks. |
Measured Values
| AmphoB Standard | AmphoB+Fluc400 | AmphoB + Fluc800 | |
|---|---|---|---|
|
Number of Participants Analyzed
[units: participants] |
46 | 48 | 41 |
|
Number of Subjects Meeting the Key Efficacy Endpoint of Treatment Success
[units: Subjects] |
|||
| Day 14 - Success | 19 | 13 | 22 |
| Day 42 - Success | 33 | 35 | 33 |
| Day 70 - Success | 33 | 36 | 32 |
No statistical analysis provided for Number of Subjects Meeting the Key Efficacy Endpoint of Treatment Success
| 6. Secondary: | Number of Subjects Reporting Immune Reconstitution Inflammatory Syndrome (IRIS) [ Time Frame: 14, 42, and 70 days ] |
| Measure Type | Secondary |
|---|---|
| Measure Title | Number of Subjects Reporting Immune Reconstitution Inflammatory Syndrome (IRIS) |
| Measure Description |
Number of subjects reporting immune reconstitution inflammatory syndrome (IRIS) following treatment. Day = Day relative to first dose of study drug |
| Time Frame | 14, 42, and 70 days |
| Safety Issue | Yes |
Population Description
| Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
|---|
| The Regulatory Safety population includes all subjects who were randomized, who receive at least 1 dose of study drug, and who have any on-study data |
Reporting Groups
| Description | |
|---|---|
| AmphoB Standard | Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed. |
| AmphoB+Fluc400 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks. |
| AmphoB + Fluc800 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks. |
Measured Values
| AmphoB Standard | AmphoB+Fluc400 | AmphoB + Fluc800 | |
|---|---|---|---|
|
Number of Participants Analyzed
[units: participants] |
45 | 47 | 49 |
|
Number of Subjects Reporting Immune Reconstitution Inflammatory Syndrome (IRIS)
[units: Subjects] |
|||
| Day 1 through 70 | 2 | 0 | 1 |
| Day 1-14 | 0 | 0 | 0 |
| Day 15-42 | 1 | 0 | 0 |
| Day 43-70 | 1 | 0 | 1 |
No statistical analysis provided for Number of Subjects Reporting Immune Reconstitution Inflammatory Syndrome (IRIS)
| 7. Secondary: | Mean Days of Hospitalization [ Time Frame: 7, 14, 42, and 70 days ] |
| Measure Type | Secondary |
|---|---|
| Measure Title | Mean Days of Hospitalization |
| Measure Description | Mean days of hospitalization. Includes days subject was hospitalized prior to study enrollment for current hospital stay. |
| Time Frame | 7, 14, 42, and 70 days |
| Safety Issue | No |
Population Description
| Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
|---|
| The mITT population includes all subjects who are randomized to a treatment arm and receive any dose of study drug, who provide any outcome data, and who are determined to have met 2 key criteria for inclusion in the primary analysis - diagnosis of culture-proven cryptococcal meningitis and proven HIV infection. |
Reporting Groups
| Description | |
|---|---|
| AmphoB Standard | Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed. |
| AmphoB+Fluc400 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks. |
| AmphoB + Fluc800 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks. |
Measured Values
| AmphoB Standard | AmphoB+Fluc400 | AmphoB + Fluc800 | |
|---|---|---|---|
|
Number of Participants Analyzed
[units: participants] |
46 | 48 | 41 |
|
Mean Days of Hospitalization
[units: Days] Mean (Standard Deviation) |
|||
| Day 7 | 8.9 (1.61) | 8.8 (2.39) | 8.1 (2.53) |
| Day 14 | 15.4 (1.78) | 15.1 (3.27) | 13.6 (4.37) |
| Day 42 | 16.3 (4.22) | 17.4 (5.91) | 16.5 (7.03) |
| Day 70 | 16.7 (4.54) | 20.1 (11.63) | 16.6 (8.24) |
No statistical analysis provided for Mean Days of Hospitalization
| 8. Secondary: | Number of Cryptococcal Isolates With Antifungal Susceptibility [ Time Frame: Days 14 and 70 ] |
| Measure Type | Secondary |
|---|---|
| Measure Title | Number of Cryptococcal Isolates With Antifungal Susceptibility |
| Measure Description | Isolates were collected at days 14 and 70 for assessment of antifungal susceptibility. |
| Time Frame | Days 14 and 70 |
| Safety Issue | No |
Population Description
| Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
|---|
| The study team has since determined that the assay that was to be utilized did not have sufficient sensitivity/specificity for its intended purpose and therefore these results will not be generated. |
Reporting Groups
| Description | |
|---|---|
| AmphoB Standard | Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed. |
| AmphoB+Fluc400 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks. |
| AmphoB + Fluc800 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks. |
Measured Values
| AmphoB Standard | AmphoB+Fluc400 | AmphoB + Fluc800 | |
|---|---|---|---|
|
Number of Participants Analyzed
[units: participants] |
0 | 0 | 0 |
|
Number of Cryptococcal Isolates With Antifungal Susceptibility
[units: Isolates] |
No statistical analysis provided for Number of Cryptococcal Isolates With Antifungal Susceptibility
| 9. Secondary: | Mean Change in Neurological Exam Score From Baseline - Day 14 [ Time Frame: Baseline and Day 14 ] |
| Measure Type | Secondary |
|---|---|
| Measure Title | Mean Change in Neurological Exam Score From Baseline - Day 14 |
| Measure Description | Neurological assessment by Mini-mental Status Exam (MMSE). This is collected as a continuous variable with values from 0-30; where lower scores indicate greater impairment. |
| Time Frame | Baseline and Day 14 |
| Safety Issue | No |
Population Description
| Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
|---|
| The number of subjects tested in the modified Intent to Treat (mITT) population includes all subjects who are randomized to a treatment arm & receive any dose of study drug, who provide any outcome data, & who are determined to have met 2 key criteria for inclusion in the primary analysis: diagnosis of cryptococcal meningitis & HIV infection. |
Reporting Groups
| Description | |
|---|---|
| AmphoB Standard | Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed. |
| AmphoB+Fluc400 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks. |
| AmphoB + Fluc800 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks. |
Measured Values
| AmphoB Standard | AmphoB+Fluc400 | AmphoB + Fluc800 | |
|---|---|---|---|
|
Number of Participants Analyzed
[units: participants] |
40 | 43 | 40 |
|
Mean Change in Neurological Exam Score From Baseline - Day 14
[units: Scores on a scale] Mean (Standard Deviation) |
0.5 (4.07) | 2.1 (3.74) | 3.5 (6.25) |
No statistical analysis provided for Mean Change in Neurological Exam Score From Baseline - Day 14
| 10. Secondary: | Mean Change in Neurological Exam Score From Baseline - Day 42 [ Time Frame: Baseline and Day 42 ] |
| Measure Type | Secondary |
|---|---|
| Measure Title | Mean Change in Neurological Exam Score From Baseline - Day 42 |
| Measure Description | Neurological assessment by Mini-mental Status Exam (MMSE). This is collected as a continuous variable with values from 0-30; where lower scores indicate greater impairment. |
| Time Frame | Baseline and Day 42 |
| Safety Issue | No |
Population Description
| Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
|---|
| The number of subjects tested in the modified Intent to Treat (mITT) population includes all subjects who are randomized to a treatment arm & receive any dose of study drug, who provide any outcome data, & who are determined to have met 2 key criteria for inclusion in the primary analysis: diagnosis of cryptococcal meningitis & HIV infection. |
Reporting Groups
| Description | |
|---|---|
| AmphoB Standard | Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed. |
| AmphoB+Fluc400 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks. |
| AmphoB + Fluc800 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks. |
Measured Values
| AmphoB Standard | AmphoB+Fluc400 | AmphoB + Fluc800 | |
|---|---|---|---|
|
Number of Participants Analyzed
[units: participants] |
37 | 39 | 37 |
|
Mean Change in Neurological Exam Score From Baseline - Day 42
[units: Scores on a scale] Mean (Standard Deviation) |
1.6 (2.58) | 1.8 (4.42) | 3.3 (7.9) |
No statistical analysis provided for Mean Change in Neurological Exam Score From Baseline - Day 42
| 11. Secondary: | Mean Change in Neurological Exam Score From Baseline - Day 70 [ Time Frame: Baseline and Day 70 ] |
| Measure Type | Secondary |
|---|---|
| Measure Title | Mean Change in Neurological Exam Score From Baseline - Day 70 |
| Measure Description | Neurological assessment by Mini-mental Status Exam (MMSE). This is collected as a continuous variable with values from 0-30; where lower scores indicate greater impairment. |
| Time Frame | Baseline and Day 70 |
| Safety Issue | No |
Population Description
| Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
|---|
| The number of subjects tested in the modified Intent to Treat (mITT) population includes all subjects who are randomized to a treatment arm & receive any dose of study drug, who provide any outcome data, & who are determined to have met 2 key criteria for inclusion in the primary analysis: diagnosis of cryptococcal meningitis & HIV infection. |
Reporting Groups
| Description | |
|---|---|
| AmphoB Standard | Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed. |
| AmphoB+Fluc400 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks. |
| AmphoB + Fluc800 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks. |
Measured Values
| AmphoB Standard | AmphoB+Fluc400 | AmphoB + Fluc800 | |
|---|---|---|---|
|
Number of Participants Analyzed
[units: participants] |
37 | 34 | 30 |
|
Mean Change in Neurological Exam Score From Baseline - Day 70
[units: Scores on a scale] Mean (Standard Deviation) |
1.5 (3.28) | 2.2 (3.58) | 4.2 (6.84) |
No statistical analysis provided for Mean Change in Neurological Exam Score From Baseline - Day 70
| 12. Secondary: | Mean Change in Neurological Exam Score From Baseline - Day 168 [ Time Frame: Baseline and Day 168 ] |
| Measure Type | Secondary |
|---|---|
| Measure Title | Mean Change in Neurological Exam Score From Baseline - Day 168 |
| Measure Description | Neurological assessment by Mini-mental Status Exam (MMSE). This is collected as a continuous variable with values from 0-30; where lower scores indicate greater impairment. |
| Time Frame | Baseline and Day 168 |
| Safety Issue | No |
Population Description
| Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
|---|
| The number of subjects tested in the modified Intent to Treat (mITT) population includes all subjects who are randomized to a treatment arm & receive any dose of study drug, who provide any outcome data, & who are determined to have met 2 key criteria for inclusion in the primary analysis: diagnosis of cryptococcal meningitis & HIV infection. |
Reporting Groups
| Description | |
|---|---|
| AmphoB Standard | Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed. |
| AmphoB+Fluc400 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks. |
| AmphoB + Fluc800 | Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks. |
Measured Values
| AmphoB Standard | AmphoB+Fluc400 | AmphoB + Fluc800 | |
|---|---|---|---|
|
Number of Participants Analyzed
[units: participants] |
33 | 27 | 28 |
|
Mean Change in Neurological Exam Score From Baseline - Day 168
[units: Scores on a scale] Mean (Standard Deviation) |
2.0 (2.28) | 2.8 (3.92) | 4.4 (7.58) |
No statistical analysis provided for Mean Change in Neurological Exam Score From Baseline - Day 168
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Limitations and Caveats
| Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data |
|---|
| No text entered. |