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Trial record 7 of 58 for:    "Aspergillosis" | "Cytochrome P-450 CYP3A Inhibitors"

Anidulafungin Plus Voriconazole Versus Voriconazole For The Treatment Of Invasive Aspergillosis

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ClinicalTrials.gov Identifier: NCT00531479
Recruitment Status : Completed
First Posted : September 18, 2007
Results First Posted : April 30, 2012
Last Update Posted : April 30, 2012
Sponsor:
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 Aspergillosis
Interventions Drug: voriconazole
Drug: anidulafungin
Enrollment 459
Recruitment Details  
Pre-assignment Details Participants were stratified at study entry for host and transplant variables known to have an independent impact on the probablity of death due to invasive aspergillosis (IA) (allogenic hematopoietic stem cell transplant versus other, and pulmonary IA).
Arm/Group Title Voriconazole/Anidulafungin Voriconazole / Placebo
Hide Arm/Group Description Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy.
Period Title: Overall Study
Started 230 229
Treated 228 226
Completed 154 146
Not Completed 76 83
Reason Not Completed
Death             68             71
Lost to Follow-up             0             2
Other             0             1
Withdrawal by Subject             6             6
Did not receive treatment             2             3
Arm/Group Title Voriconazole/Anidulafungin Voriconazole / Placebo Total
Hide Arm/Group Description Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. Total of all reporting groups
Overall Number of Baseline Participants 228 226 454
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 228 participants 226 participants 454 participants
52.0  (15.4) 51.0  (15.9) 51.5  (15.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 228 participants 226 participants 454 participants
Female
94
  41.2%
95
  42.0%
189
  41.6%
Male
134
  58.8%
131
  58.0%
265
  58.4%
1.Primary Outcome
Title All-cause Mortality at Week 6 in Participants With Proven or Probable Invasive Aspergillosis
Hide Description Number of deaths measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1.
Time Frame Day 1 to Day 42 (Week 6)
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (MITT) population: all randomized participants with proven or probable IA confirmed by Day 7 following enrollment who received at least 1 dose of study medication. N=number of participants in MITT population at Week 6. Participants not known to have died were censored at last study visit (Day 84).
Arm/Group Title Voriconazole/Anidulafungin Voriconazole / Placebo
Hide Arm/Group Description:
Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy.
Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy.
Overall Number of Participants Analyzed 135 142
Measure Type: Number
Unit of Measure: participants
26 39
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Voriconazole/Anidulafungin, Voriconazole / Placebo
Comments All-cause mortality calculated using the Kaplan-Meier (KM) product limit estimator on Day 42 (Week 6) within each stratum and weighted by the harmonic mean of the sample sizes in the strata. Treatment difference (stratified) based on a weighted difference in proportions. Stratification variables were site of infection and host factors.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0434
Comments P-value based on a 1-sided test and tested against a 1-sided alpha of 0.025 to determine statistical significance.
Method Z test for difference in proportions
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -8.74
Confidence Interval (2-Sided) 95%
-18.99 to 1.51
Estimation Comments The 95% CI was based on using Greenwood’s formula for the variance of the KM estimator.
2.Secondary Outcome
Title Global Response at Week 6
Hide Description Number of participants with a successful response (complete or partial global response). Complete response = resolution of all clinical signs and symptoms and >90% of lesions due to IA that were visible on radiologic studies at baseline (BL); partial response = clinical improvement and >50% improvement in radiological findings present at BL.
Time Frame Baseline, Day 42 (Week 6)
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; N = number of participants in MITT population at Week 6. Missing data and participants who died at Week 6 were treated as failure.
Arm/Group Title Voriconazole/Anidulafungin Voriconazole / Placebo
Hide Arm/Group Description:
Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy.
Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy.
Overall Number of Participants Analyzed 135 142
Measure Type: Number
Unit of Measure: participants
44 61
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Voriconazole/Anidulafungin, Voriconazole / Placebo
Comments Treatment difference (stratified) based on a weighted difference in proportions. Stratification variables: site of infection and host factors.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -10.23
Confidence Interval (2-Sided) 95%
-21.6 to 1.15
Estimation Comments 95% confidence interval based on the difference in success rates using the normal approximation to the binoial distribution.
3.Secondary Outcome
Title All-cause Mortality at Week 6 in Participants With Possible, Probable, or Proven Invasive Aspergillosis (IA)
Hide Description Number of deaths due to any cause measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1.
Time Frame Day 1 to Day 42 (Week 6)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: participants in MITT analysis set plus participants with possible IA who could not be upgraded to probable or proven IA within 7 days and had received at least 1 dose of study medication. N=number of participants in ITT population at Week 6.
Arm/Group Title Voriconazole/Anidulafungin Voriconazole / Placebo
Hide Arm/Group Description:
Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy.
Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy.
Overall Number of Participants Analyzed 215 207
Measure Type: Number
Unit of Measure: participants
44 47
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Voriconazole/Anidulafungin, Voriconazole / Placebo
Comments Treatment difference (stratified) based on a weighted difference in proportions. Stratification variables: site of infection and host factors.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2611
Comments P-Value based on a 1-sided test and tested against a 1-sided alpha of 0.025 to determine statistical significance.
Method Z test for difference in proportions
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.6
Confidence Interval (2-Sided) 95%
-10.77 to 5.56
Estimation Comments 95% confidence interval based on using Greenwood’s formula for the variance of the Kaplan Meier estimator.
4.Secondary Outcome
Title All-cause Mortality at Week 12 in Participants With Probable or Proven Invasive Aspergillosis (IA)
Hide Description Number of deaths due to any cause measured 12 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1.
Time Frame Day 1 to Day 84 (Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; N=number of participants in MITT population at Week 12.
Arm/Group Title Voriconazole/Anidulafungin Voriconazole / Placebo
Hide Arm/Group Description:
Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy.
Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy.
Overall Number of Participants Analyzed 135 142
Measure Type: Number
Unit of Measure: participants
39 55
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Voriconazole/Anidulafungin, Voriconazole / Placebo
Comments Treatment difference (stratified) based on a weighted difference in proportions. Stratification variables: site of infection and host factors.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0383
Comments P-Value based on a 1-sided test and tested against a 1-sided alpha of 0.025 to determine statistical significance.
Method Z test for difference in proportions
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -10.18
Confidence Interval (2-Sided) 95%
-21.44 to 1.09
Estimation Comments 95% confidence intervalbased on using Greenwood’s formula for the variance of the Kaplan Meier estimator.
5.Secondary Outcome
Title Mortality Due to Invasive Aspergillosis (IA) at Week 6 in Participants With Probable or Proven IA
Hide Description Number of deaths due to Invasive Aspergillosis measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1.
Time Frame Day 1 to Day 42 (Week 6)
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; N = number of participants in MITT population at Week 6. Participants who died due to causes other than IA before Week 6 were censored at their time of death in this analysis.
Arm/Group Title Voriconazole/Anidulafungin Voriconazole / Placebo
Hide Arm/Group Description:
Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy.
Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy.
Overall Number of Participants Analyzed 135 142
Measure Type: Number
Unit of Measure: participants
23 33
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Voriconazole/Anidulafungin, Voriconazole / Placebo
Comments Treatment difference (stratified) based on a weighted difference in proportions. Stratification variables: site of infection and host factors.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1029
Comments P-Value based on a one-sided test and tested against a 1-sided alpha of 0.025 to determine statistical significance.
Method Z test for difference in proportions
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.24
Confidence Interval (2-Sided) 95%
-15.9 to 3.42
Estimation Comments 95% confidence interval based on Greenwood’s formula for the variance of the Kaplan Meier estimator.
6.Secondary Outcome
Title Time to Death: All-Cause Mortality
Hide Description Survival time from start of treatment. Time to death defined as date of death due to any cause minus first treatment date + 1.
Time Frame Day 1 to Day 84 (Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; N = number of participants in MITT population at time of assessment.
Arm/Group Title Voriconazole/Anidulafungin Voriconazole / Placebo
Hide Arm/Group Description:
Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy.
Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy.
Overall Number of Participants Analyzed 135 142
Median (Full Range)
Unit of Measure: days
30.0
(2 to 84)
30.0
(3 to 79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Voriconazole/Anidulafungin, Voriconazole / Placebo
Comments Hazard Ratio: hazard of death in the Voriconazole/Anidulafungin arm relative to the Voriconazole/Placebo arm, adjusted for host factor status and site of infection. Participants who died beyond Day 84 were censored.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.083
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.696
Confidence Interval (2-Sided) 95%
0.46 to 1.04
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Time to Death Due to Invasive Aspergillosis (IA)
Hide Description Survival time from start of treatment. Time to death defined as date of death due to IA minus first treatment date + 1.
Time Frame Day 1 to Day 84 (Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
MITT; N = number of participants in MITT population at time of assessment. Participants who died due to causes other than IA were defined as censored at time of death.
Arm/Group Title Voriconazole/Anidulafungin Voriconazole / Placebo
Hide Arm/Group Description:
Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy.
Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy.
Overall Number of Participants Analyzed 135 142
Median (Full Range)
Unit of Measure: days
14.0
(2 to 40)
18.5
(4 to 45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Voriconazole/Anidulafungin, Voriconazole / Placebo
Comments Analysis based on Cox proportional hazards model. Participants who died beyond day 84 were censored.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.164
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.687
Confidence Interval (2-Sided) 95%
0.40 to 1.16
Estimation Comments 95% confidence interval based on Greenwood’s formula.
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Voriconazole/Anidulafungin Voriconazole / Placebo
Hide Arm/Group Description Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy.
All-Cause Mortality
Voriconazole/Anidulafungin Voriconazole / Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Voriconazole/Anidulafungin Voriconazole / Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   115/228 (50.44%)   104/226 (46.02%) 
Blood and lymphatic system disorders     
Anaemia * 1  2/228 (0.88%)  0/226 (0.00%) 
Blood disorder * 1  0/228 (0.00%)  2/226 (0.88%) 
Disseminated intravascular coagulation * 1  1/228 (0.44%)  0/226 (0.00%) 
Febrile neutropenia * 1  2/228 (0.88%)  6/226 (2.65%) 
Neutropenia * 1  0/228 (0.00%)  3/226 (1.33%) 
Pancytopenia * 1  0/228 (0.00%)  3/226 (1.33%) 
Thrombotic microangiopathy * 1  0/228 (0.00%)  1/226 (0.44%) 
Thrombotic thrombocytopenic purpura * 1  2/228 (0.88%)  0/226 (0.00%) 
Cardiac disorders     
Arrhythmia * 1  0/228 (0.00%)  1/226 (0.44%) 
Atrial fibrillation * 1  4/228 (1.75%)  2/226 (0.88%) 
Bradycardia * 1  1/228 (0.44%)  0/226 (0.00%) 
Cardiac arrest * 1  2/228 (0.88%)  1/226 (0.44%) 
Cardio-respiratory arrest * 1  0/228 (0.00%)  1/226 (0.44%) 
Cardiopulmonary failure * 1  1/228 (0.44%)  0/226 (0.00%) 
Extrasystoles * 1  1/228 (0.44%)  0/226 (0.00%) 
Myocardial ischaemia * 1  0/228 (0.00%)  1/226 (0.44%) 
Pericardial effusion * 1  1/228 (0.44%)  0/226 (0.00%) 
Pulseless electrical activity * 1  1/228 (0.44%)  0/226 (0.00%) 
Supraventricular tachycardia * 1  1/228 (0.44%)  1/226 (0.44%) 
Tachycardia * 1  2/228 (0.88%)  2/226 (0.88%) 
Ventricular fibrillation * 1  1/228 (0.44%)  0/226 (0.00%) 
Eye disorders     
Blindness * 1  1/228 (0.44%)  0/226 (0.00%) 
Blindness unilateral * 1  1/228 (0.44%)  0/226 (0.00%) 
Gastrointestinal disorders     
Abdominal pain * 1  1/228 (0.44%)  1/226 (0.44%) 
Ascites * 1  0/228 (0.00%)  1/226 (0.44%) 
Diarrhoea * 1  0/228 (0.00%)  3/226 (1.33%) 
Duodenal ulcer haemorrhage * 1  1/228 (0.44%)  0/226 (0.00%) 
Faecaloma * 1  1/228 (0.44%)  0/226 (0.00%) 
Gastric haemorrhage * 1  1/228 (0.44%)  0/226 (0.00%) 
Gastrointestinal haemorrhage * 1  0/228 (0.00%)  2/226 (0.88%) 
Haematemesis * 1  1/228 (0.44%)  0/226 (0.00%) 
Ileitis * 1  0/228 (0.00%)  1/226 (0.44%) 
Ileus paralytic * 1  1/228 (0.44%)  0/226 (0.00%) 
Lower gastrointestinal haemorrhage * 1  1/228 (0.44%)  0/226 (0.00%) 
Megacolon * 1  1/228 (0.44%)  0/226 (0.00%) 
Neutropenic colitis * 1  1/228 (0.44%)  0/226 (0.00%) 
Small intestinal obstruction * 1  0/228 (0.00%)  1/226 (0.44%) 
Upper gastrointestinal haemorrhage * 1  1/228 (0.44%)  0/226 (0.00%) 
Vomiting * 1  1/228 (0.44%)  1/226 (0.44%) 
General disorders     
Asthenia * 1  0/228 (0.00%)  2/226 (0.88%) 
Chest pain * 1  1/228 (0.44%)  0/226 (0.00%) 
Death * 1  0/228 (0.00%)  1/226 (0.44%) 
Disease progression * 1  2/228 (0.88%)  1/226 (0.44%) 
Fatigue * 1  1/228 (0.44%)  0/226 (0.00%) 
General physical health deterioration * 1  1/228 (0.44%)  2/226 (0.88%) 
Multi-organ failure * 1  5/228 (2.19%)  4/226 (1.77%) 
Pyrexia * 1  3/228 (1.32%)  4/226 (1.77%) 
Sudden cardiac death * 1  0/228 (0.00%)  1/226 (0.44%) 
Hepatobiliary disorders     
Cholecystitis * 1  0/228 (0.00%)  1/226 (0.44%) 
Cholecystitis acute * 1  0/228 (0.00%)  2/226 (0.88%) 
Hepatic failure * 1  2/228 (0.88%)  0/226 (0.00%) 
Hepatic function abnormal * 1  1/228 (0.44%)  1/226 (0.44%) 
Hepatic vein occlusion * 1  1/228 (0.44%)  0/226 (0.00%) 
Hepatotoxicity * 1  1/228 (0.44%)  0/226 (0.00%) 
Hyperbilirubinaemia * 1  1/228 (0.44%)  0/226 (0.00%) 
Liver disorder * 1  1/228 (0.44%)  0/226 (0.00%) 
Immune system disorders     
Graft versus host disease * 1  0/228 (0.00%)  1/226 (0.44%) 
Infections and infestations     
Aspergillosis * 1  6/228 (2.63%)  5/226 (2.21%) 
Bacteraemia * 1  2/228 (0.88%)  0/226 (0.00%) 
Bacterial sepsis * 1  1/228 (0.44%)  1/226 (0.44%) 
Cytomegalovirus infection * 1  1/228 (0.44%)  1/226 (0.44%) 
Device related infection * 1  1/228 (0.44%)  0/226 (0.00%) 
Disseminated tuberculosis * 1  1/228 (0.44%)  0/226 (0.00%) 
Endocarditis * 1  0/228 (0.00%)  1/226 (0.44%) 
Enterococcal bacteraemia * 1  1/228 (0.44%)  0/226 (0.00%) 
Enterococcal sepsis * 1  1/228 (0.44%)  0/226 (0.00%) 
Escherichia sepsis * 1  1/228 (0.44%)  0/226 (0.00%) 
Fungal infection * 1  1/228 (0.44%)  1/226 (0.44%) 
Gastroenteritis * 1  1/228 (0.44%)  0/226 (0.00%) 
Genital herpes * 1  0/228 (0.00%)  1/226 (0.44%) 
H1N1 influenza * 1  1/228 (0.44%)  0/226 (0.00%) 
Hepatic infection fungal * 1  1/228 (0.44%)  0/226 (0.00%) 
Herpes zoster * 1  2/228 (0.88%)  0/226 (0.00%) 
Klebsiella bacteraemia * 1  1/228 (0.44%)  0/226 (0.00%) 
Lung abscess * 1  0/228 (0.00%)  1/226 (0.44%) 
Lung infection * 1  1/228 (0.44%)  0/226 (0.00%) 
Meningitis fungal * 1  1/228 (0.44%)  0/226 (0.00%) 
Neutropenic sepsis * 1  1/228 (0.44%)  0/226 (0.00%) 
Nocardiosis * 1  1/228 (0.44%)  0/226 (0.00%) 
Oral herpes * 1  0/228 (0.00%)  1/226 (0.44%) 
Pneumocystis jiroveci pneumonia * 1  0/228 (0.00%)  1/226 (0.44%) 
Pneumonia * 1  5/228 (2.19%)  5/226 (2.21%) 
Pneumonia staphylococcal * 1  0/228 (0.00%)  1/226 (0.44%) 
Sepsis * 1  9/228 (3.95%)  7/226 (3.10%) 
Septic shock * 1  10/228 (4.39%)  14/226 (6.19%) 
Sinusitis * 1  0/228 (0.00%)  1/226 (0.44%) 
Sinusitis aspergillus * 1  0/228 (0.00%)  1/226 (0.44%) 
Staphylococcal bacteraemia * 1  0/228 (0.00%)  1/226 (0.44%) 
Staphylococcal infection * 1  0/228 (0.00%)  1/226 (0.44%) 
Staphylococcal sepsis * 1  0/228 (0.00%)  2/226 (0.88%) 
Streptococcal sepsis * 1  1/228 (0.44%)  0/226 (0.00%) 
Systemic candida * 1  1/228 (0.44%)  0/226 (0.00%) 
Tuberculosis * 1  1/228 (0.44%)  0/226 (0.00%) 
Zygomycosis * 1  1/228 (0.44%)  0/226 (0.00%) 
Injury, poisoning and procedural complications     
Complications of transplant surgery * 1  1/228 (0.44%)  0/226 (0.00%) 
Fall * 1  1/228 (0.44%)  0/226 (0.00%) 
Injury * 1  0/228 (0.00%)  1/226 (0.44%) 
Subdural haematoma * 1  1/228 (0.44%)  0/226 (0.00%) 
Wound * 1  1/228 (0.44%)  0/226 (0.00%) 
Investigations     
Blood creatine phosphokinase increased * 1  1/228 (0.44%)  0/226 (0.00%) 
C-reactive protein increased * 1  1/228 (0.44%)  1/226 (0.44%) 
Cytomegalovirus test positive * 1  1/228 (0.44%)  0/226 (0.00%) 
Electrocardiogram QT prolonged * 1  1/228 (0.44%)  0/226 (0.00%) 
Hepatic enzyme increased * 1  0/228 (0.00%)  1/226 (0.44%) 
Lipase increased * 1  0/228 (0.00%)  1/226 (0.44%) 
Liver function test abnormal * 1  1/228 (0.44%)  1/226 (0.44%) 
Oxygen saturation decreased * 1  0/228 (0.00%)  1/226 (0.44%) 
Procalcitonin increased * 1  0/228 (0.00%)  1/226 (0.44%) 
Transaminases increased * 1  0/228 (0.00%)  1/226 (0.44%) 
Metabolism and nutrition disorders     
Hypoglycaemia * 1  0/228 (0.00%)  1/226 (0.44%) 
Hypokalaemia * 1  0/228 (0.00%)  1/226 (0.44%) 
Hyponatraemia * 1  0/228 (0.00%)  1/226 (0.44%) 
Hypovolaemia * 1  1/228 (0.44%)  0/226 (0.00%) 
Lactic acidosis * 1  2/228 (0.88%)  0/226 (0.00%) 
Metabolic acidosis * 1  2/228 (0.88%)  0/226 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  1/228 (0.44%)  0/226 (0.00%) 
Muscular weakness * 1  0/228 (0.00%)  1/226 (0.44%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute leukaemia * 1  1/228 (0.44%)  1/226 (0.44%) 
Acute lymphocytic leukaemia * 1  1/228 (0.44%)  2/226 (0.88%) 
Acute myeloid leukaemia * 1  6/228 (2.63%)  4/226 (1.77%) 
B-cell lymphoma refractory * 1  0/228 (0.00%)  1/226 (0.44%) 
Blast cell crisis * 1  1/228 (0.44%)  0/226 (0.00%) 
Central nervous system lymphoma * 1  1/228 (0.44%)  0/226 (0.00%) 
Chronic lymphocytic leukaemia * 1  1/228 (0.44%)  0/226 (0.00%) 
Chronic lymphocytic leukaemia recurrent * 1  2/228 (0.88%)  0/226 (0.00%) 
Leukaemia * 1  1/228 (0.44%)  0/226 (0.00%) 
Leukaemia plasmacytic * 1  1/228 (0.44%)  0/226 (0.00%) 
Lymphoma * 1  3/228 (1.32%)  0/226 (0.00%) 
Multiple myeloma * 1  0/228 (0.00%)  2/226 (0.88%) 
Neoplasm malignant * 1  1/228 (0.44%)  0/226 (0.00%) 
Non-Hodgkin’s lymphoma * 1  1/228 (0.44%)  0/226 (0.00%) 
Nervous system disorders     
Aphasia * 1  0/228 (0.00%)  1/226 (0.44%) 
Cerebellar infarction * 1  0/228 (0.00%)  1/226 (0.44%) 
Cerebral artery embolism * 1  0/228 (0.00%)  1/226 (0.44%) 
Cerebral haemorrhage * 1  2/228 (0.88%)  1/226 (0.44%) 
Cerebral infarction * 1  1/228 (0.44%)  0/226 (0.00%) 
Convulsion * 1  3/228 (1.32%)  2/226 (0.88%) 
Dizziness * 1  1/228 (0.44%)  0/226 (0.00%) 
Encephalopathy * 1  1/228 (0.44%)  2/226 (0.88%) 
Epilepsy * 1  0/228 (0.00%)  1/226 (0.44%) 
Grand mal convulsion * 1  1/228 (0.44%)  1/226 (0.44%) 
Hepatic encephalopathy * 1  1/228 (0.44%)  0/226 (0.00%) 
Ischaemic stroke * 1  0/228 (0.00%)  1/226 (0.44%) 
Loss of consciousness * 1  0/228 (0.00%)  1/226 (0.44%) 
Petit mal epilepsy * 1  1/228 (0.44%)  0/226 (0.00%) 
Toxic neuropathy * 1  0/228 (0.00%)  1/226 (0.44%) 
Psychiatric disorders     
Confusional state * 1  0/228 (0.00%)  1/226 (0.44%) 
Hallucination * 1  1/228 (0.44%)  0/226 (0.00%) 
Hallucination, visual * 1  1/228 (0.44%)  0/226 (0.00%) 
Renal and urinary disorders     
Acute prerenal failure * 1  1/228 (0.44%)  0/226 (0.00%) 
Cystitis haemorrhagic * 1  1/228 (0.44%)  0/226 (0.00%) 
Hydronephrosis * 1  1/228 (0.44%)  0/226 (0.00%) 
Nephritic syndrome * 1  1/228 (0.44%)  0/226 (0.00%) 
Oliguria * 1  1/228 (0.44%)  1/226 (0.44%) 
Renal failure * 1  2/228 (0.88%)  2/226 (0.88%) 
Renal failure acute * 1  5/228 (2.19%)  0/226 (0.00%) 
Renal impairment * 1  1/228 (0.44%)  1/226 (0.44%) 
Reproductive system and breast disorders     
Vaginal haemorrhage * 1  1/228 (0.44%)  0/226 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome * 1  2/228 (0.88%)  4/226 (1.77%) 
Acute respiratory failure * 1  2/228 (0.88%)  1/226 (0.44%) 
Bronchospasm * 1  1/228 (0.44%)  0/226 (0.00%) 
Cough * 1  1/228 (0.44%)  0/226 (0.00%) 
Dyspnoea * 1  3/228 (1.32%)  4/226 (1.77%) 
Haemoptysis * 1  3/228 (1.32%)  3/226 (1.33%) 
Hypercapnia * 1  2/228 (0.88%)  0/226 (0.00%) 
Hypoxia * 1  2/228 (0.88%)  3/226 (1.33%) 
Lung infiltration * 1  0/228 (0.00%)  1/226 (0.44%) 
Pleural effusion * 1  2/228 (0.88%)  2/226 (0.88%) 
Pneumonitis * 1  1/228 (0.44%)  0/226 (0.00%) 
Pulmonary alveolar haemorrhage * 1  0/228 (0.00%)  2/226 (0.88%) 
Pulmonary embolism * 1  1/228 (0.44%)  1/226 (0.44%) 
Pulmonary haemorrhage * 1  2/228 (0.88%)  0/226 (0.00%) 
Pulmonary infarction * 1  0/228 (0.00%)  1/226 (0.44%) 
Pulmonary oedema * 1  0/228 (0.00%)  2/226 (0.88%) 
Respiratory disorder * 1  2/228 (0.88%)  0/226 (0.00%) 
Respiratory distress * 1  3/228 (1.32%)  6/226 (2.65%) 
Respiratory failure * 1  11/228 (4.82%)  14/226 (6.19%) 
Tachypnoea * 1  0/228 (0.00%)  1/226 (0.44%) 
Vascular disorders     
Aortic occlusion * 1  1/228 (0.44%)  0/226 (0.00%) 
Haematoma * 1  1/228 (0.44%)  0/226 (0.00%) 
Hypotension * 1  2/228 (0.88%)  1/226 (0.44%) 
Iliac artery thrombosis * 1  0/228 (0.00%)  1/226 (0.44%) 
Shock * 1  1/228 (0.44%)  0/226 (0.00%) 
Shock haemorrhagic * 1  1/228 (0.44%)  0/226 (0.00%) 
Subclavian vein thrombosis * 1  1/228 (0.44%)  0/226 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Voriconazole/Anidulafungin Voriconazole / Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   194/228 (85.09%)   192/226 (84.96%) 
Blood and lymphatic system disorders     
Anaemia * 1  7/228 (3.07%)  13/226 (5.75%) 
Cardiac disorders     
Tachycardia * 1  12/228 (5.26%)  19/226 (8.41%) 
Eye disorders     
Vision blurred * 1  14/228 (6.14%)  11/226 (4.87%) 
Gastrointestinal disorders     
Abdominal pain * 1  14/228 (6.14%)  12/226 (5.31%) 
Abdominal pain upper * 1  9/228 (3.95%)  15/226 (6.64%) 
Constipation * 1  35/228 (15.35%)  30/226 (13.27%) 
Diarrhoea * 1  39/228 (17.11%)  37/226 (16.37%) 
Dyspepsia * 1  6/228 (2.63%)  12/226 (5.31%) 
Nausea * 1  38/228 (16.67%)  42/226 (18.58%) 
Vomiting * 1  32/228 (14.04%)  23/226 (10.18%) 
General disorders     
Chest pain * 1  16/228 (7.02%)  9/226 (3.98%) 
Chills * 1  13/228 (5.70%)  10/226 (4.42%) 
Fatigue * 1  5/228 (2.19%)  14/226 (6.19%) 
Mucosal inflammation * 1  10/228 (4.39%)  15/226 (6.64%) 
Oedema * 1  12/228 (5.26%)  14/226 (6.19%) 
Oedema peripheral * 1  34/228 (14.91%)  34/226 (15.04%) 
Pain * 1  10/228 (4.39%)  13/226 (5.75%) 
Pyrexia * 1  28/228 (12.28%)  42/226 (18.58%) 
Injury, poisoning and procedural complications     
Fall * 1  12/228 (5.26%)  4/226 (1.77%) 
Investigations     
Aspartate aminotransferase increased * 1  12/228 (5.26%)  13/226 (5.75%) 
Blood alkaline phosphatase increased * 1  20/228 (8.77%)  6/226 (2.65%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  15/228 (6.58%)  14/226 (6.19%) 
Hypokalaemia * 1  37/228 (16.23%)  30/226 (13.27%) 
Hypomagnesaemia * 1  18/228 (7.89%)  15/226 (6.64%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  13/228 (5.70%)  12/226 (5.31%) 
Pain in extremity * 1  16/228 (7.02%)  11/226 (4.87%) 
Nervous system disorders     
Headache * 1  16/228 (7.02%)  26/226 (11.50%) 
Psychiatric disorders     
Agitation * 1  13/228 (5.70%)  7/226 (3.10%) 
Anxiety * 1  12/228 (5.26%)  15/226 (6.64%) 
Confusional state * 1  10/228 (4.39%)  15/226 (6.64%) 
Hallucination, visual * 1  7/228 (3.07%)  12/226 (5.31%) 
Insomnia * 1  29/228 (12.72%)  22/226 (9.73%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  15/228 (6.58%)  22/226 (9.73%) 
Dyspnoea * 1  12/228 (5.26%)  24/226 (10.62%) 
Epistaxis * 1  20/228 (8.77%)  20/226 (8.85%) 
Skin and subcutaneous tissue disorders     
Petechiae * 1  5/228 (2.19%)  12/226 (5.31%) 
Rash * 1  30/228 (13.16%)  31/226 (13.72%) 
Vascular disorders     
Hypertension * 1  32/228 (14.04%)  21/226 (9.29%) 
Hypotension * 1  30/228 (13.16%)  19/226 (8.41%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.1
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
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00531479     History of Changes
Other Study ID Numbers: A8851009
First Submitted: September 14, 2007
First Posted: September 18, 2007
Results First Submitted: April 3, 2012
Results First Posted: April 30, 2012
Last Update Posted: April 30, 2012