Trial Outcomes & Findings for Comparison of Fluconazole vs Voriconazole to Treat Fungal Infections for Blood and Marrow Transplants (BMT CTN 0101) (NCT NCT00075803)

NCT ID: NCT00075803

Last Updated: 2023-01-04

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

600 participants

Primary outcome timeframe

180 days

Results posted on

2023-01-04

Participant Flow

Participants were enrolled from November 2003 through September 2006

Participant milestones

Participant milestones
Measure
Fluconazole
fluconazole prophylaxis
Voriconazole
voriconazole prophylaxis
Overall Study
STARTED
295
305
Overall Study
COMPLETED
295
305
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Fluconazole
n=295 Participants
fluconazole prophylaxis
Voriconazole
n=305 Participants
voriconazole prophylaxis
Total
n=600 Participants
Total of all reporting groups
Age, Customized
43 years
n=5 Participants
43 years
n=7 Participants
43 years
n=5 Participants
Age, Customized
<18 years
24 participants
n=5 Participants
27 participants
n=7 Participants
51 participants
n=5 Participants
Age, Customized
≥18 years
271 participants
n=5 Participants
278 participants
n=7 Participants
549 participants
n=5 Participants
Sex: Female, Male
Female
134 Participants
n=5 Participants
135 Participants
n=7 Participants
269 Participants
n=5 Participants
Sex: Female, Male
Male
161 Participants
n=5 Participants
170 Participants
n=7 Participants
331 Participants
n=5 Participants
Race/Ethnicity, Customized
White
265 participants
n=5 Participants
276 participants
n=7 Participants
541 participants
n=5 Participants
Race/Ethnicity, Customized
Other
30 participants
n=5 Participants
29 participants
n=7 Participants
59 participants
n=5 Participants
Graft Source
Bone marrow
109 participants
n=5 Participants
106 participants
n=7 Participants
215 participants
n=5 Participants
Graft Source
Peripheral blood
186 participants
n=5 Participants
197 participants
n=7 Participants
383 participants
n=5 Participants
Graft Source
Cord blood
0 participants
n=5 Participants
2 participants
n=7 Participants
2 participants
n=5 Participants
Primary Disease
Acute myeloid leukemia
101 participants
n=5 Participants
133 participants
n=7 Participants
234 participants
n=5 Participants
Primary Disease
Acute lymphoblastic leukemia
64 participants
n=5 Participants
58 participants
n=7 Participants
122 participants
n=5 Participants
Primary Disease
Chronic myelogenous leukemia
60 participants
n=5 Participants
43 participants
n=7 Participants
103 participants
n=5 Participants
Primary Disease
Myelodysplastic syndrome
49 participants
n=5 Participants
49 participants
n=7 Participants
98 participants
n=5 Participants
Primary Disease
Non-Hodgkin lymphoma
21 participants
n=5 Participants
22 participants
n=7 Participants
43 participants
n=5 Participants
Human Leukocyte Antigen (HLA) Match
6 of 6
282 participants
n=5 Participants
293 participants
n=7 Participants
575 participants
n=5 Participants
Human Leukocyte Antigen (HLA) Match
5 of 6
13 participants
n=5 Participants
12 participants
n=7 Participants
25 participants
n=5 Participants
Karnofsky/Lansky Performance Status
90% - 100%
249 participants
n=5 Participants
268 participants
n=7 Participants
517 participants
n=5 Participants
Karnofsky/Lansky Performance Status
< 90%
46 participants
n=5 Participants
37 participants
n=7 Participants
83 participants
n=5 Participants

PRIMARY outcome

Timeframe: 180 days

Population: All randomized patients were included in the analysis

Outcome measures

Outcome measures
Measure
Fluconazole
n=295 Participants
fluconazole prophylaxis
Voriconazole
n=305 Participants
voriconazole prophylaxis
Fungal-free Survival (Percentage of Participants Alive and Free From Proven, Probable, or Presumptive Invasive Fungal Infection) at 180 Days Post-transplant
74.9 percentage of patients
Interval 69.6 to 79.5
78.2 percentage of patients
Interval 73.1 to 82.4

SECONDARY outcome

Timeframe: 1 year

Incidence of proven, probably, or presumptive IFI

Outcome measures

Outcome measures
Measure
Fluconazole
n=295 Participants
fluconazole prophylaxis
Voriconazole
n=305 Participants
voriconazole prophylaxis
Frequency of Invasive Fungal Infections (IFI)
13.7 percentage of patients
Interval 9.8 to 17.6
12.7 percentage of patients
Interval 9.0 to 16.4

SECONDARY outcome

Timeframe: 100, 180, and 365 days

Outcome measures

Outcome measures
Measure
Fluconazole
n=295 Participants
fluconazole prophylaxis
Voriconazole
n=305 Participants
voriconazole prophylaxis
Percentage of Patients With Invasive Fungal Infection at 100, 180, and 365 Days
100 days
9.5 percentage of patients
Interval 6.2 to 12.8
5.6 percentage of patients
Interval 3.1 to 8.1
Percentage of Patients With Invasive Fungal Infection at 100, 180, and 365 Days
180 days
11.2 percentage of patients
Interval 7.7 to 14.7
7.3 percentage of patients
Interval 4.4 to 10.2
Percentage of Patients With Invasive Fungal Infection at 100, 180, and 365 Days
365 days
13.7 percentage of patients
Interval 9.8 to 17.6
12.7 percentage of patients
Interval 9.0 to 16.4

SECONDARY outcome

Timeframe: 100, 180, and 365 days

Outcome measures

Outcome measures
Measure
Fluconazole
n=295 Participants
fluconazole prophylaxis
Voriconazole
n=305 Participants
voriconazole prophylaxis
Overall Survival
100 days
85.4 percentage of patients
Interval 80.9 to 89.0
90.1 percentage of patients
Interval 86.2 to 93.0
Overall Survival
180 days
80.0 percentage of patients
Interval 75.0 to 84.1
81.2 percentage of patients
Interval 76.3 to 85.1
Overall Survival
365 days
70.2 percentage of patients
Interval 64.6 to 75.1
67.8 percentage of patients
Interval 62.1 to 72.8

SECONDARY outcome

Timeframe: 100, 180, and 365 days

Outcome measures

Outcome measures
Measure
Fluconazole
n=295 Participants
fluconazole prophylaxis
Voriconazole
n=305 Participants
voriconazole prophylaxis
Relapse Free Survival
100 days
83.1 percentage of patients
Interval 78.3 to 86.9
86.1 percentage of patients
Interval 81.7 to 89.6
Relapse Free Survival
180 days
74.9 percentage of patients
Interval 69.6 to 79.5
73.9 percentage of patients
Interval 68.5 to 78.5
Relapse Free Survival
365 days
63.3 percentage of patients
Interval 57.4 to 68.6
61.2 percentage of patients
Interval 55.5 to 66.5

SECONDARY outcome

Timeframe: 1 year

Outcome measures

Outcome measures
Measure
Fluconazole
n=295 Participants
fluconazole prophylaxis
Voriconazole
n=305 Participants
voriconazole prophylaxis
Frequency of Use of Amphotericin B or Caspofungin
30.2 percentage of patients
Interval 24.9 to 35.5
24.1 percentage of patients
Interval 19.2 to 29.0

SECONDARY outcome

Timeframe: 180 days

Outcome measures

Outcome measures
Measure
Fluconazole
n=295 Participants
fluconazole prophylaxis
Voriconazole
n=305 Participants
voriconazole prophylaxis
Duration of Use of Amphotericin B or Caspofungin
Number of days on study drug
91 days
Interval 27.0 to 100.0
96 days
Interval 34.0 to 101.0
Duration of Use of Amphotericin B or Caspofungin
Start day of empiric antifungal therapy
16 days
Interval 10.0 to 33.0
12 days
Interval 8.0 to 39.0
Duration of Use of Amphotericin B or Caspofungin
Days of empiric antifungal therapy
7 days
Interval 4.0 to 17.0
7 days
Interval 5.0 to 15.0

SECONDARY outcome

Timeframe: 100 and 365 days

Outcome measures

Outcome measures
Measure
Fluconazole
n=295 Participants
fluconazole prophylaxis
Voriconazole
n=305 Participants
voriconazole prophylaxis
Time to and Severity of Acute and Chronic Graft vs Host Disease (GVHD)
Acute GVHD grade III-IV at day 100
42 participants
27 participants
Time to and Severity of Acute and Chronic Graft vs Host Disease (GVHD)
Chronic GVHD at 1 year
138 participants
137 participants
Time to and Severity of Acute and Chronic Graft vs Host Disease (GVHD)
Acute GVHD grade II-IV at day 100
132 participants
116 participants

SECONDARY outcome

Timeframe: 1 year

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.

Outcome measures

Outcome measures
Measure
Fluconazole
n=295 Participants
fluconazole prophylaxis
Voriconazole
n=305 Participants
voriconazole prophylaxis
Utility of Galactomannan Assay in Diagnosis of Aspergillus and Response to Therapy
GM+
43 participants
35 participants
Utility of Galactomannan Assay in Diagnosis of Aspergillus and Response to Therapy
GM-
252 participants
270 participants

SECONDARY outcome

Timeframe: 28 days

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 180 days

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: day 42

Outcome measures

Outcome measures
Measure
Fluconazole
n=295 Participants
fluconazole prophylaxis
Voriconazole
n=305 Participants
voriconazole prophylaxis
Failure to Engraft
11 participants
9 participants

SECONDARY outcome

Timeframe: 1 year

Outcome measures

Outcome measures
Measure
Fluconazole
n=295 Participants
fluconazole prophylaxis
Voriconazole
n=305 Participants
voriconazole prophylaxis
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
IFI before engraftment
12 participants
8 participants
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
IFI after relapse/progression
2 participants
8 participants
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
IFI who had failure to engraft
2 participants
1 participants
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
IFI after aGVHD (grades II-IV)
11 participants
14 participants
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
IFI while on study drug (up to day 100)
19 participants
10 participants
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
IFI after premature withdrawal of study drug
11 participants
16 participants
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
IFI after start other prophylaxis (not study drug)
8 participants
11 participants
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
IFI after empiric therapy
13 participants
12 participants

Adverse Events

Fluconazole

Serious events: 78 serious events
Other events: 196 other events
Deaths: 0 deaths

Voriconazole

Serious events: 73 serious events
Other events: 199 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Fluconazole
n=295 participants at risk
fluconazole prophylaxis
Voriconazole
n=305 participants at risk
voriconazole prophylaxis
Cardiac disorders
Cardiovascular arrhythmia
0.34%
1/295 • 1 year
0.00%
0/305 • 1 year
Nervous system disorders
Intracranial hemorrhage
0.34%
1/295 • 1 year
0.00%
0/305 • 1 year
Cardiac disorders
Cardiac arrest
0.34%
1/295 • 1 year
0.33%
1/305 • 1 year
Vascular disorders
Pulmoary embolus
1.0%
3/295 • 1 year
0.33%
1/305 • 1 year
Congenital, familial and genetic disorders
troponin level grade 4
0.34%
1/295 • 1 year
0.00%
0/305 • 1 year
Vascular disorders
hypotension
0.34%
1/295 • 1 year
0.00%
0/305 • 1 year
Nervous system disorders
Guillian-Barre syndrome
0.34%
1/295 • 1 year
0.00%
0/305 • 1 year
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PTLD
0.34%
1/295 • 1 year
0.00%
0/305 • 1 year
Renal and urinary disorders
acute renal failure
0.34%
1/295 • 1 year
0.00%
0/305 • 1 year
Nervous system disorders
confusion
0.34%
1/295 • 1 year
0.00%
0/305 • 1 year
Nervous system disorders
seizure
0.34%
1/295 • 1 year
0.00%
0/305 • 1 year
Metabolism and nutrition disorders
hyperglycemia
0.68%
2/295 • 1 year
0.00%
0/305 • 1 year
Respiratory, thoracic and mediastinal disorders
Hypoxia
15.3%
45/295 • 1 year
12.8%
39/305 • 1 year
Musculoskeletal and connective tissue disorders
Back Pain
0.34%
1/295 • 1 year
0.00%
0/305 • 1 year
Hepatobiliary disorders
Cholelithiasis
0.34%
1/295 • 1 year
0.00%
0/305 • 1 year
Hepatobiliary disorders
Cholecystitis
0.00%
0/295 • 1 year
0.33%
1/305 • 1 year
Cardiac disorders
AV Block - third Degree
0.00%
0/295 • 1 year
0.33%
1/305 • 1 year
Psychiatric disorders
Acute Mental Status Change
0.00%
0/295 • 1 year
0.33%
1/305 • 1 year
Renal and urinary disorders
Urinary Frequency/urgency
0.00%
0/295 • 1 year
0.33%
1/305 • 1 year
Investigations
Elevated Magnesium
0.00%
0/295 • 1 year
0.33%
1/305 • 1 year
Vascular disorders
Deep Vein Thrombosis
0.00%
0/295 • 1 year
0.33%
1/305 • 1 year
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal Cell Carcinoma
0.00%
0/295 • 1 year
0.33%
1/305 • 1 year
Nervous system disorders
Cerebrovascular Ischemia
0.00%
0/295 • 1 year
0.33%
1/305 • 1 year
Blood and lymphatic system disorders
Thrombotic Thrombocytopenic Purpura
0.00%
0/295 • 1 year
0.33%
1/305 • 1 year
Nervous system disorders
Sagittal Sinus Thrombosis
0.00%
0/295 • 1 year
0.33%
1/305 • 1 year
General disorders
Death at home, unexpected
0.00%
0/295 • 1 year
0.33%
1/305 • 1 year
Musculoskeletal and connective tissue disorders
Pain, Site Right Kidney
0.00%
0/295 • 1 year
0.33%
1/305 • 1 year
Surgical and medical procedures
Appendectomy
0.00%
0/295 • 1 year
0.33%
1/305 • 1 year
Eye disorders
Photopsia
0.00%
0/295 • 1 year
0.66%
2/305 • 1 year
Nervous system disorders
Somnolence
2.0%
6/295 • 1 year
1.6%
5/305 • 1 year
Psychiatric disorders
Psychosis
0.68%
2/295 • 1 year
0.33%
1/305 • 1 year
Nervous system disorders
Seizures
0.00%
0/295 • 1 year
0.33%
1/305 • 1 year
Nervous system disorders
Confusion
1.4%
4/295 • 1 year
1.6%
5/305 • 1 year
Cardiac disorders
EKG Abnormality
2.7%
8/295 • 1 year
1.6%
5/305 • 1 year
Cardiac disorders
Arrythmia
3.4%
10/295 • 1 year
2.3%
7/305 • 1 year
Vascular disorders
Hypotension
5.4%
16/295 • 1 year
5.2%
16/305 • 1 year
Cardiac disorders
Left Ventricular Systolic Dysfunction
1.0%
3/295 • 1 year
0.66%
2/305 • 1 year
Renal and urinary disorders
Renal Failure
3.4%
10/295 • 1 year
2.3%
7/305 • 1 year
Renal and urinary disorders
Hemorrhagic Cystitis
0.00%
0/295 • 1 year
0.00%
0/305 • 1 year
Hepatobiliary disorders
Hepatic Dysfunction
5.8%
17/295 • 1 year
5.6%
17/305 • 1 year
Gastrointestinal disorders
Mucositis/Stomatitis
3.7%
11/295 • 1 year
5.2%
16/305 • 1 year
Vascular disorders
Hemorrhage
4.1%
12/295 • 1 year
3.0%
9/305 • 1 year
Blood and lymphatic system disorders
HUS/TTP/thrombotic microangiopathy
2.0%
6/295 • 1 year
1.3%
4/305 • 1 year
Vascular disorders
Vascular Leak Syndrome
2.4%
7/295 • 1 year
2.3%
7/305 • 1 year
Respiratory, thoracic and mediastinal disorders
Dyspnea
14.6%
43/295 • 1 year
11.8%
36/305 • 1 year
General disorders
Allergic Reaction / Hypersensitivity
0.00%
0/295 • 1 year
0.00%
0/305 • 1 year
Vascular disorders
Hypertension
0.00%
0/295 • 1 year
0.00%
0/305 • 1 year
General disorders
Fever
0.00%
0/295 • 1 year
0.33%
1/305 • 1 year
General disorders
Rigors/Chills
0.00%
0/295 • 1 year
0.00%
0/305 • 1 year
Gastrointestinal disorders
Nausea
0.00%
0/295 • 1 year
0.00%
0/305 • 1 year
Gastrointestinal disorders
Vomitting
0.00%
0/295 • 1 year
0.33%
1/305 • 1 year

Other adverse events

Other adverse events
Measure
Fluconazole
n=295 participants at risk
fluconazole prophylaxis
Voriconazole
n=305 participants at risk
voriconazole prophylaxis
Eye disorders
Photopsia
6.1%
18/295 • 1 year
6.2%
19/305 • 1 year
Nervous system disorders
Somnolence
8.1%
24/295 • 1 year
9.8%
30/305 • 1 year
Psychiatric disorders
Psychosis
6.8%
20/295 • 1 year
8.9%
27/305 • 1 year
Nervous system disorders
Seizures
3.1%
9/295 • 1 year
2.0%
6/305 • 1 year
Nervous system disorders
Confusion
19.3%
57/295 • 1 year
16.1%
49/305 • 1 year
Cardiac disorders
EKG Abnormality
10.2%
30/295 • 1 year
9.8%
30/305 • 1 year
Cardiac disorders
Arrhythmia
1.4%
4/295 • 1 year
2.3%
7/305 • 1 year
Vascular disorders
Hypotension
8.1%
24/295 • 1 year
3.0%
9/305 • 1 year
Cardiac disorders
Left Ventricular Systolic Dysfunction
2.7%
8/295 • 1 year
0.33%
1/305 • 1 year
Renal and urinary disorders
Hemorrhagic Cystitis
6.4%
19/295 • 1 year
3.3%
10/305 • 1 year
Hepatobiliary disorders
Hepatic Dysfunction
29.5%
87/295 • 1 year
33.1%
101/305 • 1 year
Hepatobiliary disorders
Liver Abnormality
5.8%
17/295 • 1 year
3.9%
12/305 • 1 year
Gastrointestinal disorders
Mucositis/Stomatitis
22.4%
66/295 • 1 year
20.3%
62/305 • 1 year
Respiratory, thoracic and mediastinal disorders
Hypoxia
6.8%
20/295 • 1 year
5.9%
18/305 • 1 year
Respiratory, thoracic and mediastinal disorders
Dyspnea
11.5%
34/295 • 1 year
7.5%
23/305 • 1 year
General disorders
Allergic Reaction / Hypersensitivity
1.7%
5/295 • 1 year
1.6%
5/305 • 1 year
Vascular disorders
Hypertension
2.4%
7/295 • 1 year
1.3%
4/305 • 1 year
General disorders
Fever
9.2%
27/295 • 1 year
5.9%
18/305 • 1 year
General disorders
Rigors, chills
4.7%
14/295 • 1 year
0.98%
3/305 • 1 year
Gastrointestinal disorders
Nausea
8.5%
25/295 • 1 year
5.6%
17/305 • 1 year
Gastrointestinal disorders
Vomiting
5.1%
15/295 • 1 year
2.6%
8/305 • 1 year

Additional Information

Nancy DiFronzo, PhD

NHLBI

Phone: 301-435-0065

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place