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Trial record 1 of 1 for:    NCT00150345
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Immediate vs. Deferred Empirical Antifungal Treatment With Voriconazole In Neutropenic Patients (IDEA)

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ClinicalTrials.gov Identifier: NCT00150345
Recruitment Status : Completed
First Posted : September 8, 2005
Results First Posted : August 18, 2010
Last Update Posted : January 19, 2012
Sponsor:
Collaborator:
Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Possible Fungal Infection
Intervention Drug: voriconazole (Vfend)
Enrollment 147
Recruitment Details 810 participants screened; 81 assigned to immediate voriconazole treatment and 66 to deferred voriconazole treatment. Study should be considered a pilot study; planned sample size (n=200) was not based on statistical power considerations.
Pre-assignment Details Screening phase started with cytoreductive treatment; screening phase ended at onset of fever or if reconstitution of leukocytes to >1000 per microliter (1000/uL) or neutrophils to >500/uL. Randomization occurred within 18 hours after onset of fever (if febrile or had positive polymerase chain reaction (PCR) assay prior to onset of fever).
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL. Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Period Title: Overall Study
Started 81 66
Completed 47 34
Not Completed 34 32
Reason Not Completed
Death             5             2
Adverse Event             8             6
Lack of Efficacy             5             4
Withdrawal by Subject             3             4
Laboratory abnormality             1             2
Other             12             14
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment Total
Hide Arm/Group Description Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL. Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL. Total of all reporting groups
Overall Number of Baseline Participants 81 66 147
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 81 participants 66 participants 147 participants
Between 18 and 44 years 29 17 46
Between 45 and 64 years 31 35 66
>=65 years 21 14 35
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 81 participants 66 participants 147 participants
Female
39
  48.1%
29
  43.9%
68
  46.3%
Male
42
  51.9%
37
  56.1%
79
  53.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 81 participants 66 participants 147 participants
White 81 65 146
Other 0 1 1
Weight  
Mean (Full Range)
Unit of measure:  Kilograms (kg)
Number Analyzed 81 participants 66 participants 147 participants
77.1
(42.0 to 112.5)
79.2
(45.3 to 152.0)
78.1
(42.0 to 152.0)
Height  
Mean (Full Range)
Unit of measure:  Centimeters (cm)
Number Analyzed 81 participants 66 participants 147 participants
172.1
(150.0 to 196.0)
171.9
(153.0 to 198.0)
172.0
(150.0 to 198.0)
1.Primary Outcome
Title Number of Participants With Proven or Probable Invasive Fungal Infections (IFI): Complete Case Analysis
Hide Description Number of participants with proven (deep tissue infection, fungemia, or endemic fungal infections) or probable IFI (at least 1 host criterion [fever, body temperature <36 or >38 degrees Celsius, graft-versus-host disease, use of corticosteroids]; and 1 microbiological criterion [fungal or yeasts]; or clinical criteria [abnormal site consistent with infection]) as defined by European Organization for Research and Treatment of Cancer Mycosis Study Group (EORTC/MSG) criteria. Complete case analysis: must be evaluable until Day 28 or had developed a proven or probable IFI by the final visit.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat population (MITT): participants in ITT population (at least 1 dose of study treatment) with valid post-baseline proven or probable IFI, did not have fungemia or other IFI at screening or randomization, no antipyretic analgesics on Day 5 (or Day 9 of open-label voriconazole). N=number of complete case evaluable participants.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 43 35
Measure Type: Number
Unit of Measure: participants
6 9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Voriconazole, Deferred Voriconazole Treatment
Comments Hypothesis: H0: rv - rp = 0 vs H1: rv - rp does not equal 0, where ri is rate of IFI (i=v for voriconazole group, i=p for deferred voriconazole group). Logit model (including important covariates) used. The adjusted odds ratio and 95 percent (%) confidence interval (CI) for adjusted odds ratio calculated. If 95% CI around odds ratio does not contain a value of 1, then the null hypothesis of equal rates of IFI between immediate voriconazole and deferred voriconazole to be rejected.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.258
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.493
Confidence Interval (2-Sided) 95%
0.129 to 1.755
Estimation Comments Odds ratio computed from the logistic regression (logit model) including terms for treatment arm, concomitant fluconazole, and positive PCR before randomization. Event IFI=yes is modeled.
2.Secondary Outcome
Title Number of Participants With Defervescence Day 5 (4 Days After Initiation of Study Treatment)
Hide Description Number of participants who achieved defervescence (were afebrile). Defervescence stated if all of a participants's body temperatures within 24 hours of evaluation time were <38.0 degrees C. Defervescence was not stated and participant was discontinued from the study if participant received antipyretics (non-steroidal anti-inflammatory drugs or paracetamol).
Time Frame Day 5 (96 hours through 120 hours after start of study treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
MITT
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 68 54
Measure Type: Number
Unit of Measure: participants
32 28
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Voriconazole, Deferred Voriconazole Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.596
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.822
Confidence Interval (2-Sided) 95%
0.398 to 1.696
Estimation Comments Odds ratio computed from the logistic regression (logit model) including terms for treatment arm, concomitant fluconazole, and positive PCR before randomization. Event defervescence=yes is modeled.
3.Secondary Outcome
Title Number of Participants With Defervescence Day 9 (8 Days After Initiation of Study Treatment)
Hide Description Number of participants who achieved defervescence (were afebrile). Defervescence stated if all of a participant's body temperatures within 24 hours of evaluation time were <38.0 degrees C. Defervescence was not stated and participant was discontinued from the study if participant received antipyretics (non-steroidal anti-inflammatory drugs or paracetamol).
Time Frame Day 9 (192 hours through 216 hours after start of study treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
MITT
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 68 54
Measure Type: Number
Unit of Measure: particpants
42 34
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Voriconazole, Deferred Voriconazole Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.864
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.936
Confidence Interval (2-Sided) 95%
0.441 to 1.988
Estimation Comments Odds ratio computed from the logistic regression (logit model) including terms for treatment arm, concomitant fluconazole, and positive PCR before randomization. Event defervescence=yes is modeled.
4.Secondary Outcome
Title Time to Continuous Defervescence
Hide Description Time (in days) from start of study medication to continuous defervescence. Continuous defervescence stated if participant maintains a body temperature of <38.0 degrees C for at least 96 hours.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 68 54
Median (95% Confidence Interval)
Unit of Measure: days
6.0
(4.0 to 8.0)
5.0
(4.0 to 7.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Voriconazole, Deferred Voriconazole Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.955
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
5.Secondary Outcome
Title Number of Participants Per Reason for Lack of Defervescence
Hide Description [Not Specified]
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 68 54
Measure Type: Number
Unit of Measure: participants
Fungal infection 3 3
Bacterial infection 7 6
Viral infection 1 0
Unknown 4 4
Other 3 3
Missing evaluation response 0 1
6.Secondary Outcome
Title Number of Participants That Died on or Before Day 28 (Mortality)
Hide Description Number of participants that died on or before Day 28 after start of study treatment. A participant must be evaluable until Day 28 (final visit) or have died before the final visit.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; N=number of participants evaluable until Day 28 (final visit) or died before the final visit.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 43 29
Measure Type: Number
Unit of Measure: participants
4 1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Voriconazole, Deferred Voriconazole Treatment
Comments Difference in proportions expressed as a percent: immediate voriconazole versus (vs) deferred voriconazole treatment
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in % participants that died
Estimated Value 5.85
Confidence Interval (2-Sided) 95%
-5.08 to 16.78
Estimation Comments Approximate 2-sided confidence interval (CI).
7.Secondary Outcome
Title Time to Negative Panfungal Polymerase Chain Reaction (PCR)
Hide Description Time (in days) from start of study medication to negative panfungal PCR; assessed for participants whose most recent panfungal PCR result prior to start of study medication was positive. Defined as negative if at least 2 successive and all following panfungal PCR assessments from start of study medication until 24 hours after end of treatment are negative. Measured as first quartile of time (point in time measurement; no median or measure of dispersion calculated); median time was not estimable for deferred voriconazole treatment group.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; N=number of participants whose most recent panfungal PCR result prior to start of study medication was positive.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 10 8
Measure Type: Number
Unit of Measure: days
4.0 5.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Voriconazole, Deferred Voriconazole Treatment
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.190
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
8.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association of Positive PCR Assessments With Achievement of Continuous Defervescence (Yes)
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with achievement of continuous defervescence (response=Yes). Continuous defervescence stated if participant maintains a body temperature of <38.0 degrees C for at least 96 hours. Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; N=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 36 27
Mean (Standard Deviation)
Unit of Measure: percent of positive PCR assessments
10.6  (14.11) 8.0  (14.71)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Voriconazole, Deferred Voriconazole Treatment
Comments Continuous defervescence achieved=Yes
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.049
Comments SAS PROC REG with SELECTION=STEPWISE option of SLENTRY=0.05 and SLSTAY=0.10 utilized. Stepwise option combined forward stepping (with a 0.05 level to enter) with elimination of variables already in model that do not stay significant at 0.10 level.
Method Regression, Linear
Comments Variables: association with age, c-reactive protein, and time to continuous defervescence not significant at 0.05 level; not included in final model
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -22.031
Confidence Interval (2-Sided) 95%
-44.004 to -0.059
Parameter Dispersion
Type: Standard Error of the mean
Value: 10.888
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association of Positive PCR Assessments With Achievement of Continuous Defervescence (No)
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with achievement of continuous defervescence (response=No). Continuous defervescence stated if participant maintains a body temperature of <38.0 degrees C for at least 96 hours. Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; N=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 3 0
Mean (Standard Deviation)
Unit of Measure: percent of positive PCR assessments
21.7  (20.21)
10.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Age
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with age for participants who completed the study and have a non-missing value for percent of positive panfungal PCR.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT. Correlation of positive panfungal PCR assessments with age was not summarized as planned.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Gender
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with gender (Female or Male). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 68 54
Mean (Standard Deviation)
Unit of Measure: percent of positive PCR assessments
Female (n=21, 12) 12.3  (14.82) 4.2  (10.36)
Male (n=18, 15) 10.4  (14.75) 11.1  (17.16)
12.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Primary Underlying Neoplastic Disease
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with primary underlying neoplastic disease. Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 68 54
Mean (Standard Deviation)
Unit of Measure: percent of positive PCR assessments
Acute lymphatic leukemia (n=6, 6) 13.9  (16.39) 9.7  (15.29)
Acute myeloid leukemia (n=29, 18) 10.5  (14.39) 8.8  (15.78)
13.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Planned Allogeneic Transplants
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with allogeneic bone marrow transplant or allogeneic peripheral stem cell transplant (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 68 54
Mean (Standard Deviation)
Unit of Measure: percent of positive PCR assessments
Association Yes (n=13, 9) 10.5  (14.88) 6.5  (13.03)
Association No (n=26, 18) 11.9  (14.77) 8.8  (15.78)
14.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Concomitant Fluconazole
Hide Description Percent positive panfungal PCR assessments during treatment phase of study in association with use of concomitant (prophylaxis) fluconazole (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 68 54
Mean (Standard Deviation)
Unit of Measure: percent of positive PCR assessments
Association Yes (n=8, 4) 13.5  (15.39) 6.3  (12.50)
Association No (n=31, 23) 10.9  (14.63) 8.3  (15.28)
15.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Neutrophil Count >500 uL
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with neutrophil count >500 uL (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 68 54
Mean (Standard Deviation)
Unit of Measure: percent of positive PCR assessments
Association Yes (n=24, 20) 10.9  (14.60) 7.9  (15.17)
Association No (n=15, 7) 12.3  (15.13) 8.3  (14.43)
16.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With C-reactive Protein Level >1.25 Times the Upper Limit of Normal (x ULN)
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with c-reactive protein level (measured in milligrams per liter [mg/L]) >1.25 x ULN (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT. Correlation of positive panfungal PCR assessments with c-reactive protein level was not summarized as planned.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
17.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with fungal species (singular [one species]=sp; plural [many species]=spp) identified (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 68 54
Mean (Standard Deviation)
Unit of Measure: percent of positive PCR assessments
Aspergillus flavus: No (n=39, 27) 11.4  (14.62) 8.0  (14.71)
Aspergillus fumig: No (n=38, 27) 11.7  (14.70) 8.0  (14.71)
Aspergillus nidulans: No (n=39, 27) 11.4  (14.62) 8.0  (14.71)
Aspergillus sp: No (n=39, 27) 11.4  (14.62) 8.0  (14.71)
Aspergillus spp: No (n=37, 27) 11.6  (14.88) 8.0  (14.71)
Candida albicans: Yes (n=2, 4) 16.7  (23.57) 0.0  (0.0)
Candida albicans: No (n=37, 23) 11.2  (14.45) 9.4  (15.55)
Candida glabrata: Yes (n=2, 1) 33.3  (0.00) 0.0  (0.0)
Candida glabrata: No (n=37, 26) 10.3  (14.06) 8.3  (14.91)
Candida krusei: No (n=39, 26) 11.4  (14.62) 8.3  (14.91)
Candida spp: No (n=38, 27) 11.7  (14.70) 8.0  (14.71)
Candida tropicalis: No (n=39, 27) 11.4  (14.62) 8.0  (14.71)
18.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified (Aspergillus Spp=Yes)
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with fungal species (singular [one species]=sp; plural [many species]=spp) identified (Yes). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; N=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 2 0
Mean (Standard Deviation)
Unit of Measure: percent of positive PCR assessments
8.3  (11.79)
19.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Proven or Probable IFI (Complete Cases) Between Day 2 and Day 28
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with proven or probable IFI (complete cases) between Day 2 and Day 28 (Yes or No). Complete case analysis: participant must be evaluable until Day 28 (final visit) or have developed a proven or probable IFI by the final visit. Participant considered evaluable until Day 28 if participant completed the study and completed an assessment of IFI at Day 28 or final visit. Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 68 54
Mean (Standard Deviation)
Unit of Measure: percent of positive PCR assessments
Association Yes (n=2, 2) 0.0  (0.0) 16.7  (23.57)
Association No (n=37, 25) 12.1  (14.77) 7.3  (14.30)
20.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence Day 5 (4 Days After Initiation of Study Treatment)
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with defervescence (were afebrile) Day 5 (Yes or No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 5 (96 hours through 120 hours after start of study treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
Arm/Group Title Immediate Voriconazole Deferred Voricoazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 68 54
Mean (Standard Deviation)
Unit of Measure: percent of positive PCR assessments
Association Yes (n=28, 21) 14.5  (14.58) 8.3  (15.81)
Association No (n=11, 6) 3.6  (12.06) 6.9  (11.08)
21.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence (Yes) by Day 9 (8 Days After Initiation of Study Treatment)
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with defervescence (were afebrile) Day 9 (Yes). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 2 through Day 9 (192 hours through 216 hours after start of study treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; N=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 37 27
Mean (Standard Deviation)
Unit of Measure: percent of positive PCR assessments
11.0  (14.11) 8.0  (14.71)
22.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence (No) by Day 9 (8 Days After Initiation of Study Treatment)
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with defervescence (were afebrile) Day 9 (No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 2 through Day 9 (192 hours through 216 hours after start of study treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; N=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 2 0
Mean (Standard Deviation)
Unit of Measure: percent of positive PCR assessments
20.0  (28.28)
23.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Time to Defervescence
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with time to defervescence. Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT. Correlation of positive panfungal PCR assessments with time to defervescence was not summarized as planned.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
24.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence (No)
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with lack of continuous defervescence (No). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 2 through Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; (n)=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 68 54
Mean (Standard Deviation)
Unit of Measure: percent of positive PCR assessments
Fungal infection: No (n=39, 27) 11.4  (14.62) 8.0  (14.71)
Bacterial infection: No (n=39, 27) 11.4  (14.62) 8.0  (14.71)
Viral infection: No (n=39, 27) 11.4  (14.62) 8.0  (14.71)
Unknown infection: No (n=36, 27) 10.6  (14.11) 8.0  (14.71)
Other infection: No (n=39, 27) 11.4  (14.62) 8.0  (14.71)
25.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence: Unknown Infection (Yes)
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with lack of continuous defervescence (Yes). Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
Time Frame Day 2 through Day 28
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Hide Analysis Population Description
MITT; N=number of participants who completed the study and had a non-missing value for percent of positive panfungal PCR for immediate voriconazole and deferred voriconazole treatment, respectively.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
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Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 3 0
Mean (Standard Deviation)
Unit of Measure: percent of positive PCR assessments
21.7  (20.21)
26.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Alive)
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with mortality on or before Day 28 after start of study treatment (Alive). A participant must be evaluable until Day 28 (final visit).
Time Frame Day 2 through Day 28
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Hide Analysis Population Description
MITT; participants who completed the study and had a non-missing value for percent of positive panfungal PCR. N=number of participants for category "Alive".
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
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Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 39 27
Mean (Standard Deviation)
Unit of Measure: percent of positive PCR assessments
11.4  (14.62) 8.0  (14.71)
27.Secondary Outcome
Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Died)
Hide Description Percent of positive panfungal PCR assessments during treatment phase of study in association with mortality on or before Day 28 after start of study treatment (Died). A participant must have died before Day 28 (final visit).
Time Frame Day 2 through Day 28
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Hide Analysis Population Description
MITT; participants who completed the study and had a non-missing value for percent of positive panfungal PCR: no participants met this criteria within the category "Died".
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
28.Secondary Outcome
Title Number of Participants Assessed as Needing Further Antineoplastic Therapy as Planned
Hide Description [Not Specified]
Time Frame Day 28
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Hide Analysis Population Description
MITT
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 68 54
Measure Type: Number
Unit of Measure: participants
42 32
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Immediate Voriconazole, Deferred Voriconazole Treatment
Comments Difference in proportions expressed as a percent: immediate voriconazole vs deferred voriconazole treatment
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentages
Estimated Value 2.51
Confidence Interval (2-Sided) 95%
-14.96 to 19.97
Estimation Comments [Not Specified]
29.Secondary Outcome
Title Number of Participants With Reasons Why Antineoplastic Therapy Not Continued as Planned
Hide Description [Not Specified]
Time Frame Day 28
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Hide Analysis Population Description
MITT; data not summarized as planned; data insufficient for analysis due to missing data.
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description:
Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Baseline up to 7 days after last dose of study drug
Adverse Event Reporting Description Safety population = all randomized participants with at least 1 dose of study treatment. The same event may appear as both an AE and SAE; however, they are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another, or 1 participant may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Immediate Voriconazole Deferred Voriconazole Treatment
Hide Arm/Group Description Voriconazole intravenous (IV) loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). Continued treatment with oral (PO) voriconazole 200 mg twice a day (BID) through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees Celsius [C]) for 7 days with neutrophil counts < 500 per microliter (500/uL) or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL. Placebo IV loading dose of 6 mg/kg every 12 hours on Day 1 for the first 2 doses followed by 4 mg/kg IV every 12 hours (maintenance dose) for at least 4 days (up to Day 5). On Day 5, voriconazole IV loading dose of 6 mg/kg every 12 hours for at least 4 days (up to Day 9). Continued treatment with PO voriconazole 200 mg BID through Day 28. Treatment ended if the participant was afebrile (< 38.0 degrees C) for 7 days with neutrophil counts < 500/uL or if participant was afebrile (< 38.0 degrees C) for 2 days with neutrophil counts > 500/uL.
All-Cause Mortality
Immediate Voriconazole Deferred Voriconazole Treatment
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Immediate Voriconazole Deferred Voriconazole Treatment
Affected / at Risk (%) Affected / at Risk (%)
Total   8/81 (9.88%)   8/66 (12.12%) 
Cardiac disorders     
Coronary artery disease  1  1/81 (1.23%)  0/66 (0.00%) 
Gastrointestinal disorders     
Gastrointestinal haemorrhage  1  1/81 (1.23%)  1/66 (1.52%) 
General disorders     
Chest pain  1  0/81 (0.00%)  1/66 (1.52%) 
Multi-organ failure  1  1/81 (1.23%)  0/66 (0.00%) 
Pyrexia  1  0/81 (0.00%)  1/66 (1.52%) 
Hepatobiliary disorders     
Cholecystitis acute  1  1/81 (1.23%)  0/66 (0.00%) 
Hepatic function abnormal  1  0/81 (0.00%)  1/66 (1.52%) 
Immune system disorders     
Anaphylactic reaction  1  1/81 (1.23%)  0/66 (0.00%) 
Infections and infestations     
Abscess  1  1/81 (1.23%)  0/66 (0.00%) 
Bacteraemia  1  1/81 (1.23%)  0/66 (0.00%) 
Bacterial sepsis  1  0/81 (0.00%)  1/66 (1.52%) 
Cellulitis  1  0/81 (0.00%)  1/66 (1.52%) 
Encephalitic infection  1  0/81 (0.00%)  1/66 (1.52%) 
Enterocolitis bacterial  1  0/81 (0.00%)  1/66 (1.52%) 
Gastroenteritis norovirus  1  0/81 (0.00%)  1/66 (1.52%) 
Mucormycosis  1  1/81 (1.23%)  0/66 (0.00%) 
Pneumonia  1  1/81 (1.23%)  0/66 (0.00%) 
Sepsis  1  1/81 (1.23%)  2/66 (3.03%) 
Septic shock  1  1/81 (1.23%)  0/66 (0.00%) 
Renal and urinary disorders     
Renal failure acute  1  1/81 (1.23%)  0/66 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory failure  1  1/81 (1.23%)  0/66 (0.00%) 
Vascular disorders     
Embolism  1  1/81 (1.23%)  0/66 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Immediate Voriconazole Deferred Voriconazole Treatment
Affected / at Risk (%) Affected / at Risk (%)
Total   58/81 (71.60%)   38/66 (57.58%) 
Eye disorders     
Visual impairment  1  5/81 (6.17%)  2/66 (3.03%) 
Gastrointestinal disorders     
Abdominal pain  1  2/81 (2.47%)  5/66 (7.58%) 
Constipation  1  7/81 (8.64%)  3/66 (4.55%) 
Diarrhoea  1  22/81 (27.16%)  13/66 (19.70%) 
Nausea  1  12/81 (14.81%)  6/66 (9.09%) 
Vomiting  1  9/81 (11.11%)  5/66 (7.58%) 
General disorders     
Chest pain  1  2/81 (2.47%)  5/66 (7.58%) 
Mucosal inflammation  1  7/81 (8.64%)  3/66 (4.55%) 
Oedema  1  5/81 (6.17%)  3/66 (4.55%) 
Oedema peripheral  1  6/81 (7.41%)  1/66 (1.52%) 
Pyrexia  1  7/81 (8.64%)  5/66 (7.58%) 
Investigations     
C-reactive protein increased  1  1/81 (1.23%)  4/66 (6.06%) 
Metabolism and nutrition disorders     
Hypokalaemia  1  8/81 (9.88%)  2/66 (3.03%) 
Nervous system disorders     
Headache  1  8/81 (9.88%)  11/66 (16.67%) 
Psychiatric disorders     
Hallucination  1  5/81 (6.17%)  2/66 (3.03%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  7/81 (8.64%)  5/66 (7.58%) 
Epistaxis  1  11/81 (13.58%)  4/66 (6.06%) 
Skin and subcutaneous tissue disorders     
Rash  1  14/81 (17.28%)  6/66 (9.09%) 
Vascular disorders     
Hypertension  1  5/81 (6.17%)  3/66 (4.55%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
One participant in the Immediate Voriconazole treatment group was incorrectly included in the original Primary efficacy analysis and has now been excluded; IFI was identified on the day study treatment started (not prior to study treatment).
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.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
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Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.govCallCenter@pfizer.com
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00150345    
Other Study ID Numbers: A1501029
First Submitted: September 6, 2005
First Posted: September 8, 2005
Results First Submitted: April 5, 2010
Results First Posted: August 18, 2010
Last Update Posted: January 19, 2012