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Comparison of Fluconazole vs Voriconazole to Treat Fungal Infections for Blood and Marrow Transplants (BMT CTN 0101)

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ClinicalTrials.gov Identifier: NCT00075803
Recruitment Status : Completed
First Posted : January 13, 2004
Results First Posted : September 4, 2015
Last Update Posted : September 12, 2016
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
National Marrow Donor Program
Information provided by (Responsible Party):
Medical College of Wisconsin

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Lymphoma
Infection
Leukemia
Interventions Drug: Fluconazole
Drug: Voriconazole
Enrollment 600
Recruitment Details Participants were enrolled from November 2003 through September 2006
Pre-assignment Details  
Arm/Group Title Fluconazole Voriconazole
Hide Arm/Group Description fluconazole prophylaxis voriconazole prophylaxis
Period Title: Overall Study
Started 295 305
Completed 295 305
Not Completed 0 0
Arm/Group Title Fluconazole Voriconazole Total
Hide Arm/Group Description fluconazole prophylaxis voriconazole prophylaxis Total of all reporting groups
Overall Number of Baseline Participants 295 305 600
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 295 participants 305 participants 600 participants
43
(9 to 65)
43
(3 to 66)
43
(3 to 66)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 295 participants 305 participants 600 participants
<18 years 24 27 51
≥18 years 271 278 549
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 295 participants 305 participants 600 participants
Female
134
  45.4%
135
  44.3%
269
  44.8%
Male
161
  54.6%
170
  55.7%
331
  55.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 295 participants 305 participants 600 participants
White 265 276 541
Other 30 29 59
Graft Source  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 295 participants 305 participants 600 participants
Bone marrow 109 106 215
Peripheral blood 186 197 383
Cord blood 0 2 2
Primary Disease  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 295 participants 305 participants 600 participants
Acute myeloid leukemia 101 133 234
Acute lymphoblastic leukemia 64 58 122
Chronic myelogenous leukemia 60 43 103
Myelodysplastic syndrome 49 49 98
Non-Hodgkin lymphoma 21 22 43
Human Leukocyte Antigen (HLA) Match   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 295 participants 305 participants 600 participants
6 of 6 282 293 575
5 of 6 13 12 25
[1]
Measure Description: Patients must have a 5 or 6 of 6 HLA-matched donor. The match may be determined at serologic level for HLA-A and HLA-B loci.
Karnofsky/Lansky Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 295 participants 305 participants 600 participants
90% - 100% 249 268 517
< 90% 46 37 83
[1]
Measure Description: Assesses patient self-perceived global quality of life and functioning (excellent, very good, good, fair, poor), where 100 equals perfect quality of life.
1.Primary Outcome
Title Fungal-free Survival (Percentage of Participants Alive and Free From Proven, Probable, or Presumptive Invasive Fungal Infection) at 180 Days Post-transplant
Hide Description [Not Specified]
Time Frame 180 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized patients were included in the analysis
Arm/Group Title Fluconazole Voriconazole
Hide Arm/Group Description:
fluconazole prophylaxis
voriconazole prophylaxis
Overall Number of Participants Analyzed 295 305
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
74.9
(69.6 to 79.5)
78.2
(73.1 to 82.4)
2.Secondary Outcome
Title Frequency of Invasive Fungal Infections (IFI)
Hide Description Incidence of proven, probably, or presumptive IFI
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Fluconazole Voriconazole
Hide Arm/Group Description:
fluconazole prophylaxis
voriconazole prophylaxis
Overall Number of Participants Analyzed 295 305
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
13.7
(9.8 to 17.6)
12.7
(9.0 to 16.4)
3.Secondary Outcome
Title Percentage of Patients With Invasive Fungal Infection at 100, 180, and 365 Days
Hide Description [Not Specified]
Time Frame 100, 180, and 365 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Fluconazole Voriconazole
Hide Arm/Group Description:
fluconazole prophylaxis
voriconazole prophylaxis
Overall Number of Participants Analyzed 295 305
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
100 days
9.5
(6.2 to 12.8)
5.6
(3.1 to 8.1)
180 days
11.2
(7.7 to 14.7)
7.3
(4.4 to 10.2)
365 days
13.7
(9.8 to 17.6)
12.7
(9.0 to 16.4)
4.Secondary Outcome
Title Overall Survival
Hide Description [Not Specified]
Time Frame 100, 180, and 365 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Fluconazole Voriconazole
Hide Arm/Group Description:
fluconazole prophylaxis
voriconazole prophylaxis
Overall Number of Participants Analyzed 295 305
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
100 days
85.4
(80.9 to 89.0)
90.1
(86.2 to 93.0)
180 days
80.0
(75.0 to 84.1)
81.2
(76.3 to 85.1)
365 days
70.2
(64.6 to 75.1)
67.8
(62.1 to 72.8)
5.Secondary Outcome
Title Relapse Free Survival
Hide Description [Not Specified]
Time Frame 100, 180, and 365 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Fluconazole Voriconazole
Hide Arm/Group Description:
fluconazole prophylaxis
voriconazole prophylaxis
Overall Number of Participants Analyzed 295 305
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
100 days
83.1
(78.3 to 86.9)
86.1
(81.7 to 89.6)
180 days
74.9
(69.6 to 79.5)
73.9
(68.5 to 78.5)
365 days
63.3
(57.4 to 68.6)
61.2
(55.5 to 66.5)
6.Secondary Outcome
Title Frequency of Use of Amphotericin B or Caspofungin
Hide Description [Not Specified]
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Fluconazole Voriconazole
Hide Arm/Group Description:
fluconazole prophylaxis
voriconazole prophylaxis
Overall Number of Participants Analyzed 295 305
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
30.2
(24.9 to 35.5)
24.1
(19.2 to 29.0)
7.Secondary Outcome
Title Duration of Use of Amphotericin B or Caspofungin
Hide Description [Not Specified]
Time Frame 180 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Fluconazole Voriconazole
Hide Arm/Group Description:
fluconazole prophylaxis
voriconazole prophylaxis
Overall Number of Participants Analyzed 295 305
Mean (Inter-Quartile Range)
Unit of Measure: days
Number of days on study drug
91
(27 to 100)
96
(34 to 101)
Start day of empiric antifungal therapy
16
(10 to 33)
12
(8 to 39)
Days of empiric antifungal therapy
7
(4 to 17)
7
(5 to 15)
8.Secondary Outcome
Title Time to and Severity of Acute and Chronic Graft vs Host Disease (GVHD)
Hide Description [Not Specified]
Time Frame 100 and 365 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Fluconazole Voriconazole
Hide Arm/Group Description:
fluconazole prophylaxis
voriconazole prophylaxis
Overall Number of Participants Analyzed 295 305
Measure Type: Number
Unit of Measure: participants
Acute GVHD grade II-IV at day 100 132 116
Acute GVHD grade III-IV at day 100 42 27
Chronic GVHD at 1 year 138 137
9.Secondary Outcome
Title Utility of Galactomannan Assay in Diagnosis of Aspergillus and Response to Therapy
Hide Description Although there were 82 Galactomannan (GM) positives, 4 were excluded due to piperacillin/tazobactam administration, without other documentation of IFI, and were deemed false positives.
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Fluconazole Voriconazole
Hide Arm/Group Description:
fluconazole prophylaxis
voriconazole prophylaxis
Overall Number of Participants Analyzed 295 305
Measure Type: Number
Unit of Measure: participants
GM+ 43 35
GM- 252 270
10.Secondary Outcome
Title Time to Neutrophil Engraftment
Hide Description [Not Specified]
Time Frame 28 days
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Time to Platelet Engraftment
Hide Description [Not Specified]
Time Frame 180 days
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Failure to Engraft
Hide Description [Not Specified]
Time Frame day 42
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Fluconazole Voriconazole
Hide Arm/Group Description:
fluconazole prophylaxis
voriconazole prophylaxis
Overall Number of Participants Analyzed 295 305
Measure Type: Number
Unit of Measure: participants
11 9
13.Secondary Outcome
Title Freedom From Possible, Presumptive, Probable, or Proven Invasive Fungal Infection, Death, or Withdrawal of Study Drug Due to Toxicity, Intolerance, or an Empirical Trial of Amphotericin B or Caspofungin Greater Than 14 Consecutive Days
Hide Description [Not Specified]
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Fluconazole Voriconazole
Hide Arm/Group Description:
fluconazole prophylaxis
voriconazole prophylaxis
Overall Number of Participants Analyzed 295 305
Measure Type: Number
Unit of Measure: participants
IFI after relapse/progression 2 8
IFI before engraftment 12 8
IFI who had failure to engraft 2 1
IFI after aGVHD (grades II-IV) 11 14
IFI while on study drug (up to day 100) 19 10
IFI after premature withdrawal of study drug 11 16
IFI after start other prophylaxis (not study drug) 8 11
IFI after empiric therapy 13 12
Time Frame 1 year
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Fluconazole Voriconazole
Hide Arm/Group Description fluconazole prophylaxis voriconazole prophylaxis
All-Cause Mortality
Fluconazole Voriconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Fluconazole Voriconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   78/295 (26.44%)   73/305 (23.93%) 
Blood and lymphatic system disorders     
Thrombotic Thrombocytopenic Purpura * 1  0/295 (0.00%)  1/305 (0.33%) 
HUS/TTP/thrombotic microangiopathy  1  6/295 (2.03%)  4/305 (1.31%) 
Cardiac disorders     
Cardiovascular arrhythmia * 1  1/295 (0.34%)  0/305 (0.00%) 
Cardiac arrest * 1  1/295 (0.34%)  1/305 (0.33%) 
AV Block - third Degree * 1  0/295 (0.00%)  1/305 (0.33%) 
EKG Abnormality  1  8/295 (2.71%)  5/305 (1.64%) 
Arrythmia  1  10/295 (3.39%)  7/305 (2.30%) 
Left Ventricular Systolic Dysfunction  1  3/295 (1.02%)  2/305 (0.66%) 
Congenital, familial and genetic disorders     
troponin level grade 4 * 1  1/295 (0.34%)  0/305 (0.00%) 
Eye disorders     
Photopsia  1  0/295 (0.00%)  2/305 (0.66%) 
Gastrointestinal disorders     
Mucositis/Stomatitis  1  11/295 (3.73%)  16/305 (5.25%) 
Nausea  1  0/295 (0.00%)  0/305 (0.00%) 
Vomitting  1  0/295 (0.00%)  1/305 (0.33%) 
General disorders     
Death at home, unexpected * 1  0/295 (0.00%)  1/305 (0.33%) 
Allergic Reaction / Hypersensitivity  1  0/295 (0.00%)  0/305 (0.00%) 
Fever  1  0/295 (0.00%)  1/305 (0.33%) 
Rigors/Chills  1  0/295 (0.00%)  0/305 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis * 1  1/295 (0.34%)  0/305 (0.00%) 
Cholecystitis * 1  0/295 (0.00%)  1/305 (0.33%) 
Hepatic Dysfunction  1  17/295 (5.76%)  17/305 (5.57%) 
Investigations     
Elevated Magnesium * 1  0/295 (0.00%)  1/305 (0.33%) 
Metabolism and nutrition disorders     
hyperglycemia * 1  2/295 (0.68%)  0/305 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back Pain * 1  1/295 (0.34%)  0/305 (0.00%) 
Pain, Site Right Kidney * 1  0/295 (0.00%)  1/305 (0.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
PTLD * 1  1/295 (0.34%)  0/305 (0.00%) 
Renal Cell Carcinoma * 1  0/295 (0.00%)  1/305 (0.33%) 
Nervous system disorders     
Intracranial hemorrhage * 1  1/295 (0.34%)  0/305 (0.00%) 
Guillian-Barre syndrome * 1  1/295 (0.34%)  0/305 (0.00%) 
confusion * 1  1/295 (0.34%)  0/305 (0.00%) 
seizure * 1  1/295 (0.34%)  0/305 (0.00%) 
Cerebrovascular Ischemia * 1  0/295 (0.00%)  1/305 (0.33%) 
Sagittal Sinus Thrombosis * 1  0/295 (0.00%)  1/305 (0.33%) 
Somnolence  1  6/295 (2.03%)  5/305 (1.64%) 
Seizures  1  0/295 (0.00%)  1/305 (0.33%) 
Confusion  1  4/295 (1.36%)  5/305 (1.64%) 
Psychiatric disorders     
Acute Mental Status Change * 1  0/295 (0.00%)  1/305 (0.33%) 
Psychosis  1  2/295 (0.68%)  1/305 (0.33%) 
Renal and urinary disorders     
acute renal failure * 1  1/295 (0.34%)  0/305 (0.00%) 
Urinary Frequency/urgency * 1  0/295 (0.00%)  1/305 (0.33%) 
Renal Failure  1  10/295 (3.39%)  7/305 (2.30%) 
Hemorrhagic Cystitis  1  0/295 (0.00%)  0/305 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Hypoxia * 1  1/295 (0.34%)  0/305 (0.00%) 
Hypoxia  1  45/295 (15.25%)  39/305 (12.79%) 
Dyspnea  1  43/295 (14.58%)  36/305 (11.80%) 
Surgical and medical procedures     
Appendectomy * 1  0/295 (0.00%)  1/305 (0.33%) 
Vascular disorders     
Pulmoary embolus * 1  3/295 (1.02%)  1/305 (0.33%) 
hypotension * 1  1/295 (0.34%)  0/305 (0.00%) 
Deep Vein Thrombosis * 1  0/295 (0.00%)  1/305 (0.33%) 
Hypotension  1  16/295 (5.42%)  16/305 (5.25%) 
Hemorrhage  1  12/295 (4.07%)  9/305 (2.95%) 
Vascular Leak Syndrome  1  7/295 (2.37%)  7/305 (2.30%) 
Hypertension  1  0/295 (0.00%)  0/305 (0.00%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Fluconazole Voriconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   196/295 (66.44%)   199/305 (65.25%) 
Cardiac disorders     
EKG Abnormality  1  30/295 (10.17%)  30/305 (9.84%) 
Arrhythmia  1  4/295 (1.36%)  7/305 (2.30%) 
Left Ventricular Systolic Dysfunction  1  8/295 (2.71%)  1/305 (0.33%) 
Eye disorders     
Photopsia  1  18/295 (6.10%)  19/305 (6.23%) 
Gastrointestinal disorders     
Mucositis/Stomatitis  1  66/295 (22.37%)  62/305 (20.33%) 
Nausea  1  25/295 (8.47%)  17/305 (5.57%) 
Vomiting  1  15/295 (5.08%)  8/305 (2.62%) 
General disorders     
Allergic Reaction / Hypersensitivity  1  5/295 (1.69%)  5/305 (1.64%) 
Fever  1  27/295 (9.15%)  18/305 (5.90%) 
Rigors, chills  1  14/295 (4.75%)  3/305 (0.98%) 
Hepatobiliary disorders     
Hepatic Dysfunction  1  87/295 (29.49%)  101/305 (33.11%) 
Liver Abnormality  1  17/295 (5.76%)  12/305 (3.93%) 
Nervous system disorders     
Somnolence  1  24/295 (8.14%)  30/305 (9.84%) 
Seizures  1  9/295 (3.05%)  6/305 (1.97%) 
Confusion  1  57/295 (19.32%)  49/305 (16.07%) 
Psychiatric disorders     
Psychosis  1  20/295 (6.78%)  27/305 (8.85%) 
Renal and urinary disorders     
Hemorrhagic Cystitis  1  19/295 (6.44%)  10/305 (3.28%) 
Respiratory, thoracic and mediastinal disorders     
Hypoxia  1  20/295 (6.78%)  18/305 (5.90%) 
Dyspnea  1  34/295 (11.53%)  23/305 (7.54%) 
Vascular disorders     
Hypotension  1  24/295 (8.14%)  9/305 (2.95%) 
Hypertension  1  7/295 (2.37%)  4/305 (1.31%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title: Nancy DiFronzo, PhD
Organization: NHLBI
Phone: 301-435-0065
Responsible Party: Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT00075803     History of Changes
Obsolete Identifiers: NCT00322088
Other Study ID Numbers: BMTCTN0101
BMT CTN 0101 ( Other Identifier: Blood and Marrow Transplant Clinical Trial Network )
U01HL069294 ( U.S. NIH Grant/Contract )
5U24CA076518 ( U.S. NIH Grant/Contract )
First Submitted: January 9, 2004
First Posted: January 13, 2004
Results First Submitted: February 22, 2013
Results First Posted: September 4, 2015
Last Update Posted: September 12, 2016