Clincosm LogoSign in Get a demo

Anidulafungin Plus Voriconazole Versus Voriconazole For The Treatment Of Invasive Aspergillosis

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00531479
Collaborator
(none)
459
Enrollment
107
Locations
2
Arms
34
Duration (Months)
4.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study compares the effectiveness and safety of the combination of anidulafungin and voriconazole compared to that of voriconazole alone (which is generally considered the standard of care) for the treatment of Invasive Aspergillosis.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
459 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Prospective, Randomized Trial Comparing The Efficacy Of Anidulafungin And Voriconazole In Combination To That Of Voriconazole Alone When Used For Primary Therapy Of Proven Or Probable Invasive Aspergillosis
Study Start Date :
Jul 1, 2008
Actual Primary Completion Date :
Apr 1, 2011
Actual Study Completion Date :
May 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Voriconazole

Voriconazole monotherapy

Drug: voriconazole
First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV BID plus anidulafungin placebo IV qd. Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin placebo IV qd. Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin placebo IV qd, OR Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy.
Other Names:
  • Vfend

    		•
    Experimental: Voriconazole and Anidulafungin

    Combination therapy with voriconazole and anidulafungin

    Drug: anidulafungin
    First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV bid plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV qd thereafter. Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin 100 mg IV qd. Third and fourth weeks: 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. Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy.
    Other Names:
  • Eraxis

    • Drug: voriconazole
    First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV bid plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV qd thereafter. Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin 100 mg IV qd. Third and fourth weeks: 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. Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy.
    Other Names:
  • Vfend

    		•

    Outcome Measures

    Primary Outcome Measures

    1. All-cause Mortality at Week 6 in Participants With Proven or Probable Invasive Aspergillosis [Day 1 to Day 42 (Week 6)]

      Number of deaths measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1.

    Secondary Outcome Measures

    1. Global Response at Week 6 [Baseline, Day 42 (Week 6)]

      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.

    2. All-cause Mortality at Week 6 in Participants With Possible, Probable, or Proven Invasive Aspergillosis (IA) [Day 1 to Day 42 (Week 6)]

      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.

    3. All-cause Mortality at Week 12 in Participants With Probable or Proven Invasive Aspergillosis (IA) [Day 1 to Day 84 (Week 12)]

      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.

    4. Mortality Due to Invasive Aspergillosis (IA) at Week 6 in Participants With Probable or Proven IA [Day 1 to Day 42 (Week 6)]

      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.

    5. Time to Death: All-Cause Mortality [Day 1 to Day 84 (Week 12)]

      Survival time from start of treatment. Time to death defined as date of death due to any cause minus first treatment date + 1.

    6. Time to Death Due to Invasive Aspergillosis (IA) [Day 1 to Day 84 (Week 12)]

      Survival time from start of treatment. Time to death defined as date of death due to IA minus first treatment date + 1.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    16 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Immunocompromised state due to either 1. receipt of hematopoeitic stem cell transplantation or 2. hematologic malignancy;

    • Diagnosis of possible, probable, or proven invasive aspergillosis.

    Exclusion Criteria:

    • Patients with aspergilloma or chronic aspergillosis

    • Receipt of 4 or more days of systemic antifungal treatment for the current episode of invasive aspergillosis

    • Anticipated survival of less than 5 days or Karnofsky score <=20

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Pfizer Investigational Site Birmingham Alabama United States 35233
    2 Pfizer Investigational Site Birmingham Alabama United States 35249
    3 Pfizer Investigational Site Little Rock Arkansas United States 72205
    4 Pfizer Investigational Site La Jolla California United States 92037
    5 Pfizer Investigational Site LaJolla California United States 92093
    6 Pfizer Investigational Site San Diego California United States 92103-8976
    7 Pfizer Investigational Site San Francisco California United States 94143
    8 Pfizer Investigational Site Gainesville Florida United States 32610
    9 Pfizer Investigational Site Miami Florida United States 33136
    10 Pfizer Investigational Site Atlanta Georgia United States 30322
    11 Pfizer Investigational Site Chicago Illinois United States 60612
    12 Pfizer Investigational Site Chicago Illinois United States 60637
    13 Pfizer Investigational Site Baltimore Maryland United States 21205
    14 Pfizer Investigational Site Baltimore Maryland United States 21231-2410
    15 Pfizer Investigational Site Baltimore Maryland United States 21231
    16 Pfizer Investigational Site Baltimore Maryland United States 21287
    17 Pfizer Investigational Site Detroit Michigan United States 48201
    18 Pfizer Investigational Site Detroit Michigan United States 48202
    19 Pfizer Investigational Site Rochester New York United States 14642
    20 Pfizer Investigational Site Chapel Hill North Carolina United States 27514
    21 Pfizer Investigational Site Winston-Salem North Carolina United States 27157
    22 Pfizer Investigational Site Portland Oregon United States 97239
    23 Pfizer Investigational Site Philadelphia Pennsylvania United States 19104
    24 Pfizer Investigational Site Houston Texas United States 77030
    25 Pfizer Investigational Site Seattle Washington United States 98109
    26 Pfizer Investigational Site Seattle Washington United States 98195
    27 Pfizer Investigational Site Westmead New South Wales Australia 2145
    28 Pfizer Investigational Site Herston Queensland Australia 4029
    29 Pfizer Investigational Site Adelaide South Australia Australia 5000
    30 Pfizer Investigational Site Brugge Belgium 8000
    31 Pfizer Investigational Site Bruxelles Belgium 1000
    32 Pfizer Investigational Site Leuven Belgium 3000
    33 Pfizer Investigational Site Yvoir Belgium B-5530
    34 Pfizer Investigational Site Curitiba PR Brazil 80060-900
    35 Pfizer Investigational Site Rio de Janeiro RJ Brazil 21941-913
    36 Pfizer Investigational Site Porto Alegre RS Brazil 90020-090
    37 Pfizer Investigational Site Winnipeg Manitoba Canada R3A 1R9
    38 Pfizer Investigational Site Winnipeg Manitoba Canada R3E 0V9
    39 Pfizer Investigational Site Hamilton Ontario Canada L8N 3Z5
    40 Pfizer Investigational Site Hamilton Ontario Canada L8V 1C3
    41 Pfizer Investigational Site Montreal Quebec Canada H1T 2M4
    42 Pfizer Investigational Site Quebec Canada G1R 2J6
    43 Pfizer Investigational Site Praha 2 Czech Republic 128 20
    44 Pfizer Investigational Site Nantes Cedex 01 France 44093
    45 Pfizer Investigational Site Marseille Cedex 09 France 13273
    46 Pfizer Investigational Site Brest France 29609
    47 Pfizer Investigational Site Creteil France 94010
    48 Pfizer Investigational Site GRENOBLE Cedex 09 France 38043
    49 Pfizer Investigational Site Paris France 75475
    50 Pfizer Investigational Site Rouen Cedex France 76038
    51 Pfizer Investigational Site Strasbourg France 67098
    52 Pfizer Investigational Site Berlin Germany 10117
    53 Pfizer Investigational Site Berlin Germany 12200
    54 Pfizer Investigational Site Bremen Germany 28177
    55 Pfizer Investigational Site Dresden Germany 01307
    56 Pfizer Investigational Site Frankfurt (Oder) Germany 15236
    57 Pfizer Investigational Site Hamburg Germany 20246
    58 Pfizer Investigational Site Heidelberg Germany 69120
    59 Pfizer Investigational Site Homburg/Saar Germany 66421
    60 Pfizer Investigational Site Koeln Germany 50937
    61 Pfizer Investigational Site Mainz Germany 55101
    62 Pfizer Investigational Site Muenchen Germany 81737
    63 Pfizer Investigational Site Wuerzburg Germany 97080
    64 Pfizer Investigational Site Thessaloniki Greece 57010
    65 Pfizer Investigational Site Pune Maharashtra India 411004
    66 Pfizer Investigational Site Cuneo Italy 12100
    67 Pfizer Investigational Site Genova Italy 16132
    68 Pfizer Investigational Site Milano Italy 20132
    69 Pfizer Investigational Site Milano Italy 20162
    70 Pfizer Investigational Site Perugia Italy 06134
    71 Pfizer Investigational Site Pescara Italy 65100
    72 Pfizer Investigational Site Roma Italy 00168
    73 Pfizer Investigational Site Seoul Korea, Republic of 110-744
    74 Pfizer Investigational Site Seoul Korea, Republic of 120-752
    75 Pfizer Investigational Site Seoul Korea, Republic of 135-710
    76 Pfizer Investigational Site Seoul Korea, Republic of 138-736
    77 Pfizer Investigational Site Seoul Korea, Republic of 150-713
    78 Pfizer Investigational Site RC Leiden Netherlands NL-2300
    79 Pfizer Investigational Site Lima Peru Lima 34
    80 Pfizer Investigational Site Gdansk Poland 80-952
    81 Pfizer Investigational Site Warszawa Poland 02-097
    82 Pfizer Investigational Site Lisboa Portugal 1169-050
    83 Pfizer Investigational Site Lisboa Portugal 1649-035
    84 Pfizer Investigational Site Moscow Russian Federation 105229
    85 Pfizer Investigational Site Moscow Russian Federation 115478
    86 Pfizer Investigational Site Moscow Russian Federation 125167
    87 Pfizer Investigational Site Saint Petersburg Russian Federation 197089
    88 Pfizer Investigational Site Singapore Singapore 119074
    89 Pfizer Investigational Site Singapore Singapore 169608
    90 Pfizer Investigational Site Badalona Barcelona Spain 08916
    91 Pfizer Investigational Site Madrid Spain 28006
    92 Pfizer Investigational Site Madrid Spain 28050
    93 Pfizer Investigational Site Salamanca Spain 37007
    94 Pfizer Investigational Site Valencia Spain 46010
    95 Pfizer Investigational Site Valencia Spain 46026
    96 Pfizer Investigational Site Geneve 14 Switzerland CH-1211
    97 Pfizer Investigational Site Lausanne Switzerland 1011
    98 Pfizer Investigational Site Kuei-Shan Hsiang Taoyuan County Taiwan 333
    99 Pfizer Investigational Site Kaohsiung Taiwan 807
    100 Pfizer Investigational Site Taipei Taiwan 112
    101 Pfizer Investigational Site Bangkok Thailand 10330
    102 Pfizer Investigational Site Bangkok Thailand 10400
    103 Pfizer Investigational Site Bangkok Thailand 10700
    104 Pfizer Investigational Site Adana Turkey 01330
    105 Pfizer Investigational Site Ankara Turkey 06100
    106 Pfizer Investigational Site London United Kingdom SE5 9RS
    107 Pfizer Investigational Site Manchester United Kingdom M20 4BX

    Sponsors and Collaborators

    • Pfizer

    Investigators

    • Study Director: Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT00531479
    Other Study ID Numbers:
    • A8851009
    First Posted:
    Sep 18, 2007
    Last Update Posted:
    Apr 30, 2012
    Last Verified:
    Apr 1, 2012
    Additional relevant MeSH terms:
    Aspergillosis
    Voriconazole
    Anidulafungin

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 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
    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

    Baseline Characteristics

    Arm/Group Title Voriconazole/Anidulafungin Voriconazole / Placebo Total
    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 Participants 228 226 454
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    52.0
    (15.4)
    51.0
    (15.9)
    51.5
    (15.7)
    Sex: Female, Male (Count of Participants)
    Female
    94
    41.2%
    95
    42%
    189
    41.6%
    Male
    134
    58.8%
    131
    58%
    265
    58.4%

    Outcome Measures

    1. Primary Outcome
    Title All-cause Mortality at Week 6 in Participants With Proven or Probable Invasive Aspergillosis
    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)

    Outcome Measure Data

    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
    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.
    Measure Participants 135 142
    Number [participants]
    26
    11.4%
    39
    17.3%
    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
    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
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -8.74
    Confidence Interval (2-Sided) 95%
    -18.99 to 1.51
    Parameter Dispersion Type:
    Value:
    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
    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)

    Outcome Measure Data

    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
    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.
    Measure Participants 135 142
    Number [participants]
    44
    19.3%
    61
    27%
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -10.23
    Confidence Interval (2-Sided) 95%
    -21.6 to 1.15
    Parameter Dispersion Type:
    Value:
    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)
    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)

    Outcome Measure Data

    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
    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.
    Measure Participants 215 207
    Number [participants]
    44
    19.3%
    47
    20.8%
    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
    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
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.6
    Confidence Interval (2-Sided) 95%
    -10.77 to 5.56
    Parameter Dispersion Type:
    Value:
    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)
    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)

    Outcome Measure Data

    Analysis Population Description
    MITT; N=number of participants in MITT population at Week 12.
    Arm/Group Title Voriconazole/Anidulafungin Voriconazole / Placebo
    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.
    Measure Participants 135 142
    Number [participants]
    39
    17.1%
    55
    24.3%
    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
    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
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -10.18
    Confidence Interval (2-Sided) 95%
    -21.44 to 1.09
    Parameter Dispersion Type:
    Value:
    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
    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)

    Outcome Measure Data

    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
    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.
    Measure Participants 135 142
    Number [participants]
    23
    10.1%
    33
    14.6%
    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
    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
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -6.24
    Confidence Interval (2-Sided) 95%
    -15.9 to 3.42
    Parameter Dispersion Type:
    Value:
    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
    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)

    Outcome Measure Data

    Analysis Population Description
    MITT; N = number of participants in MITT population at time of assessment.
    Arm/Group Title Voriconazole/Anidulafungin Voriconazole / Placebo
    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.
    Measure Participants 135 142
    Median (Full Range) [days]
    30.0
    30.0
    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
    Statistical Test of Hypothesis p-Value 0.083
    Comments
    Method Cox proportional hazards model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.696
    Confidence Interval (2-Sided) 95%
    0.46 to 1.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Time to Death Due to Invasive Aspergillosis (IA)
    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)

    Outcome Measure Data

    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
    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.
    Measure Participants 135 142
    Median (Full Range) [days]
    14.0
    18.5
    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
    Statistical Test of Hypothesis p-Value 0.164
    Comments
    Method Cox proportional hazards model
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.687
    Confidence Interval (2-Sided) 95%
    0.40 to 1.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments 95% confidence interval based on Greenwood's formula.

    Adverse Events

    Time Frame
    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
    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 (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Voriconazole/Anidulafungin Voriconazole / Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 115/228 (50.4%) 104/226 (46%)
    Blood and lymphatic system disorders
    Anaemia 2/228 (0.9%) 0/226 (0%)
    Blood disorder 0/228 (0%) 2/226 (0.9%)
    Disseminated intravascular coagulation 1/228 (0.4%) 0/226 (0%)
    Febrile neutropenia 2/228 (0.9%) 6/226 (2.7%)
    Neutropenia 0/228 (0%) 3/226 (1.3%)
    Pancytopenia 0/228 (0%) 3/226 (1.3%)
    Thrombotic microangiopathy 0/228 (0%) 1/226 (0.4%)
    Thrombotic thrombocytopenic purpura 2/228 (0.9%) 0/226 (0%)
    Cardiac disorders
    Arrhythmia 0/228 (0%) 1/226 (0.4%)
    Atrial fibrillation 4/228 (1.8%) 2/226 (0.9%)
    Bradycardia 1/228 (0.4%) 0/226 (0%)
    Cardiac arrest 2/228 (0.9%) 1/226 (0.4%)
    Cardio-respiratory arrest 0/228 (0%) 1/226 (0.4%)
    Cardiopulmonary failure 1/228 (0.4%) 0/226 (0%)
    Extrasystoles 1/228 (0.4%) 0/226 (0%)
    Myocardial ischaemia 0/228 (0%) 1/226 (0.4%)
    Pericardial effusion 1/228 (0.4%) 0/226 (0%)
    Pulseless electrical activity 1/228 (0.4%) 0/226 (0%)
    Supraventricular tachycardia 1/228 (0.4%) 1/226 (0.4%)
    Tachycardia 2/228 (0.9%) 2/226 (0.9%)
    Ventricular fibrillation 1/228 (0.4%) 0/226 (0%)
    Eye disorders
    Blindness 1/228 (0.4%) 0/226 (0%)
    Blindness unilateral 1/228 (0.4%) 0/226 (0%)
    Gastrointestinal disorders
    Abdominal pain 1/228 (0.4%) 1/226 (0.4%)
    Ascites 0/228 (0%) 1/226 (0.4%)
    Diarrhoea 0/228 (0%) 3/226 (1.3%)
    Duodenal ulcer haemorrhage 1/228 (0.4%) 0/226 (0%)
    Faecaloma 1/228 (0.4%) 0/226 (0%)
    Gastric haemorrhage 1/228 (0.4%) 0/226 (0%)
    Gastrointestinal haemorrhage 0/228 (0%) 2/226 (0.9%)
    Haematemesis 1/228 (0.4%) 0/226 (0%)
    Ileitis 0/228 (0%) 1/226 (0.4%)
    Ileus paralytic 1/228 (0.4%) 0/226 (0%)
    Lower gastrointestinal haemorrhage 1/228 (0.4%) 0/226 (0%)
    Megacolon 1/228 (0.4%) 0/226 (0%)
    Neutropenic colitis 1/228 (0.4%) 0/226 (0%)
    Small intestinal obstruction 0/228 (0%) 1/226 (0.4%)
    Upper gastrointestinal haemorrhage 1/228 (0.4%) 0/226 (0%)
    Vomiting 1/228 (0.4%) 1/226 (0.4%)
    General disorders
    Asthenia 0/228 (0%) 2/226 (0.9%)
    Chest pain 1/228 (0.4%) 0/226 (0%)
    Death 0/228 (0%) 1/226 (0.4%)
    Disease progression 2/228 (0.9%) 1/226 (0.4%)
    Fatigue 1/228 (0.4%) 0/226 (0%)
    General physical health deterioration 1/228 (0.4%) 2/226 (0.9%)
    Multi-organ failure 5/228 (2.2%) 4/226 (1.8%)
    Pyrexia 3/228 (1.3%) 4/226 (1.8%)
    Sudden cardiac death 0/228 (0%) 1/226 (0.4%)
    Hepatobiliary disorders
    Cholecystitis 0/228 (0%) 1/226 (0.4%)
    Cholecystitis acute 0/228 (0%) 2/226 (0.9%)
    Hepatic failure 2/228 (0.9%) 0/226 (0%)
    Hepatic function abnormal 1/228 (0.4%) 1/226 (0.4%)
    Hepatic vein occlusion 1/228 (0.4%) 0/226 (0%)
    Hepatotoxicity 1/228 (0.4%) 0/226 (0%)
    Hyperbilirubinaemia 1/228 (0.4%) 0/226 (0%)
    Liver disorder 1/228 (0.4%) 0/226 (0%)
    Immune system disorders
    Graft versus host disease 0/228 (0%) 1/226 (0.4%)
    Infections and infestations
    Aspergillosis 6/228 (2.6%) 5/226 (2.2%)
    Bacteraemia 2/228 (0.9%) 0/226 (0%)
    Bacterial sepsis 1/228 (0.4%) 1/226 (0.4%)
    Cytomegalovirus infection 1/228 (0.4%) 1/226 (0.4%)
    Device related infection 1/228 (0.4%) 0/226 (0%)
    Disseminated tuberculosis 1/228 (0.4%) 0/226 (0%)
    Endocarditis 0/228 (0%) 1/226 (0.4%)
    Enterococcal bacteraemia 1/228 (0.4%) 0/226 (0%)
    Enterococcal sepsis 1/228 (0.4%) 0/226 (0%)
    Escherichia sepsis 1/228 (0.4%) 0/226 (0%)
    Fungal infection 1/228 (0.4%) 1/226 (0.4%)
    Gastroenteritis 1/228 (0.4%) 0/226 (0%)
    Genital herpes 0/228 (0%) 1/226 (0.4%)
    H1N1 influenza 1/228 (0.4%) 0/226 (0%)
    Hepatic infection fungal 1/228 (0.4%) 0/226 (0%)
    Herpes zoster 2/228 (0.9%) 0/226 (0%)
    Klebsiella bacteraemia 1/228 (0.4%) 0/226 (0%)
    Lung abscess 0/228 (0%) 1/226 (0.4%)
    Lung infection 1/228 (0.4%) 0/226 (0%)
    Meningitis fungal 1/228 (0.4%) 0/226 (0%)
    Neutropenic sepsis 1/228 (0.4%) 0/226 (0%)
    Nocardiosis 1/228 (0.4%) 0/226 (0%)
    Oral herpes 0/228 (0%) 1/226 (0.4%)
    Pneumocystis jiroveci pneumonia 0/228 (0%) 1/226 (0.4%)
    Pneumonia 5/228 (2.2%) 5/226 (2.2%)
    Pneumonia staphylococcal 0/228 (0%) 1/226 (0.4%)
    Sepsis 9/228 (3.9%) 7/226 (3.1%)
    Septic shock 10/228 (4.4%) 14/226 (6.2%)
    Sinusitis 0/228 (0%) 1/226 (0.4%)
    Sinusitis aspergillus 0/228 (0%) 1/226 (0.4%)
    Staphylococcal bacteraemia 0/228 (0%) 1/226 (0.4%)
    Staphylococcal infection 0/228 (0%) 1/226 (0.4%)
    Staphylococcal sepsis 0/228 (0%) 2/226 (0.9%)
    Streptococcal sepsis 1/228 (0.4%) 0/226 (0%)
    Systemic candida 1/228 (0.4%) 0/226 (0%)
    Tuberculosis 1/228 (0.4%) 0/226 (0%)
    Zygomycosis 1/228 (0.4%) 0/226 (0%)
    Injury, poisoning and procedural complications
    Complications of transplant surgery 1/228 (0.4%) 0/226 (0%)
    Fall 1/228 (0.4%) 0/226 (0%)
    Injury 0/228 (0%) 1/226 (0.4%)
    Subdural haematoma 1/228 (0.4%) 0/226 (0%)
    Wound 1/228 (0.4%) 0/226 (0%)
    Investigations
    Blood creatine phosphokinase increased 1/228 (0.4%) 0/226 (0%)
    C-reactive protein increased 1/228 (0.4%) 1/226 (0.4%)
    Cytomegalovirus test positive 1/228 (0.4%) 0/226 (0%)
    Electrocardiogram QT prolonged 1/228 (0.4%) 0/226 (0%)
    Hepatic enzyme increased 0/228 (0%) 1/226 (0.4%)
    Lipase increased 0/228 (0%) 1/226 (0.4%)
    Liver function test abnormal 1/228 (0.4%) 1/226 (0.4%)
    Oxygen saturation decreased 0/228 (0%) 1/226 (0.4%)
    Procalcitonin increased 0/228 (0%) 1/226 (0.4%)
    Transaminases increased 0/228 (0%) 1/226 (0.4%)
    Metabolism and nutrition disorders
    Hypoglycaemia 0/228 (0%) 1/226 (0.4%)
    Hypokalaemia 0/228 (0%) 1/226 (0.4%)
    Hyponatraemia 0/228 (0%) 1/226 (0.4%)
    Hypovolaemia 1/228 (0.4%) 0/226 (0%)
    Lactic acidosis 2/228 (0.9%) 0/226 (0%)
    Metabolic acidosis 2/228 (0.9%) 0/226 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/228 (0.4%) 0/226 (0%)
    Muscular weakness 0/228 (0%) 1/226 (0.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute leukaemia 1/228 (0.4%) 1/226 (0.4%)
    Acute lymphocytic leukaemia 1/228 (0.4%) 2/226 (0.9%)
    Acute myeloid leukaemia 6/228 (2.6%) 4/226 (1.8%)
    B-cell lymphoma refractory 0/228 (0%) 1/226 (0.4%)
    Blast cell crisis 1/228 (0.4%) 0/226 (0%)
    Central nervous system lymphoma 1/228 (0.4%) 0/226 (0%)
    Chronic lymphocytic leukaemia 1/228 (0.4%) 0/226 (0%)
    Chronic lymphocytic leukaemia recurrent 2/228 (0.9%) 0/226 (0%)
    Leukaemia 1/228 (0.4%) 0/226 (0%)
    Leukaemia plasmacytic 1/228 (0.4%) 0/226 (0%)
    Lymphoma 3/228 (1.3%) 0/226 (0%)
    Multiple myeloma 0/228 (0%) 2/226 (0.9%)
    Neoplasm malignant 1/228 (0.4%) 0/226 (0%)
    Non-Hodgkin's lymphoma 1/228 (0.4%) 0/226 (0%)
    Nervous system disorders
    Aphasia 0/228 (0%) 1/226 (0.4%)
    Cerebellar infarction 0/228 (0%) 1/226 (0.4%)
    Cerebral artery embolism 0/228 (0%) 1/226 (0.4%)
    Cerebral haemorrhage 2/228 (0.9%) 1/226 (0.4%)
    Cerebral infarction 1/228 (0.4%) 0/226 (0%)
    Convulsion 3/228 (1.3%) 2/226 (0.9%)
    Dizziness 1/228 (0.4%) 0/226 (0%)
    Encephalopathy 1/228 (0.4%) 2/226 (0.9%)
    Epilepsy 0/228 (0%) 1/226 (0.4%)
    Grand mal convulsion 1/228 (0.4%) 1/226 (0.4%)
    Hepatic encephalopathy 1/228 (0.4%) 0/226 (0%)
    Ischaemic stroke 0/228 (0%) 1/226 (0.4%)
    Loss of consciousness 0/228 (0%) 1/226 (0.4%)
    Petit mal epilepsy 1/228 (0.4%) 0/226 (0%)
    Toxic neuropathy 0/228 (0%) 1/226 (0.4%)
    Psychiatric disorders
    Confusional state 0/228 (0%) 1/226 (0.4%)
    Hallucination 1/228 (0.4%) 0/226 (0%)
    Hallucination, visual 1/228 (0.4%) 0/226 (0%)
    Renal and urinary disorders
    Acute prerenal failure 1/228 (0.4%) 0/226 (0%)
    Cystitis haemorrhagic 1/228 (0.4%) 0/226 (0%)
    Hydronephrosis 1/228 (0.4%) 0/226 (0%)
    Nephritic syndrome 1/228 (0.4%) 0/226 (0%)
    Oliguria 1/228 (0.4%) 1/226 (0.4%)
    Renal failure 2/228 (0.9%) 2/226 (0.9%)
    Renal failure acute 5/228 (2.2%) 0/226 (0%)
    Renal impairment 1/228 (0.4%) 1/226 (0.4%)
    Reproductive system and breast disorders
    Vaginal haemorrhage 1/228 (0.4%) 0/226 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome 2/228 (0.9%) 4/226 (1.8%)
    Acute respiratory failure 2/228 (0.9%) 1/226 (0.4%)
    Bronchospasm 1/228 (0.4%) 0/226 (0%)
    Cough 1/228 (0.4%) 0/226 (0%)
    Dyspnoea 3/228 (1.3%) 4/226 (1.8%)
    Haemoptysis 3/228 (1.3%) 3/226 (1.3%)
    Hypercapnia 2/228 (0.9%) 0/226 (0%)
    Hypoxia 2/228 (0.9%) 3/226 (1.3%)
    Lung infiltration 0/228 (0%) 1/226 (0.4%)
    Pleural effusion 2/228 (0.9%) 2/226 (0.9%)
    Pneumonitis 1/228 (0.4%) 0/226 (0%)
    Pulmonary alveolar haemorrhage 0/228 (0%) 2/226 (0.9%)
    Pulmonary embolism 1/228 (0.4%) 1/226 (0.4%)
    Pulmonary haemorrhage 2/228 (0.9%) 0/226 (0%)
    Pulmonary infarction 0/228 (0%) 1/226 (0.4%)
    Pulmonary oedema 0/228 (0%) 2/226 (0.9%)
    Respiratory disorder 2/228 (0.9%) 0/226 (0%)
    Respiratory distress 3/228 (1.3%) 6/226 (2.7%)
    Respiratory failure 11/228 (4.8%) 14/226 (6.2%)
    Tachypnoea 0/228 (0%) 1/226 (0.4%)
    Vascular disorders
    Aortic occlusion 1/228 (0.4%) 0/226 (0%)
    Haematoma 1/228 (0.4%) 0/226 (0%)
    Hypotension 2/228 (0.9%) 1/226 (0.4%)
    Iliac artery thrombosis 0/228 (0%) 1/226 (0.4%)
    Shock 1/228 (0.4%) 0/226 (0%)
    Shock haemorrhagic 1/228 (0.4%) 0/226 (0%)
    Subclavian vein thrombosis 1/228 (0.4%) 0/226 (0%)
    Other (Not Including Serious) Adverse Events
    Voriconazole/Anidulafungin Voriconazole / Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 194/228 (85.1%) 192/226 (85%)
    Blood and lymphatic system disorders
    Anaemia 7/228 (3.1%) 13/226 (5.8%)
    Cardiac disorders
    Tachycardia 12/228 (5.3%) 19/226 (8.4%)
    Eye disorders
    Vision blurred 14/228 (6.1%) 11/226 (4.9%)
    Gastrointestinal disorders
    Abdominal pain 14/228 (6.1%) 12/226 (5.3%)
    Abdominal pain upper 9/228 (3.9%) 15/226 (6.6%)
    Constipation 35/228 (15.4%) 30/226 (13.3%)
    Diarrhoea 39/228 (17.1%) 37/226 (16.4%)
    Dyspepsia 6/228 (2.6%) 12/226 (5.3%)
    Nausea 38/228 (16.7%) 42/226 (18.6%)
    Vomiting 32/228 (14%) 23/226 (10.2%)
    General disorders
    Chest pain 16/228 (7%) 9/226 (4%)
    Chills 13/228 (5.7%) 10/226 (4.4%)
    Fatigue 5/228 (2.2%) 14/226 (6.2%)
    Mucosal inflammation 10/228 (4.4%) 15/226 (6.6%)
    Oedema 12/228 (5.3%) 14/226 (6.2%)
    Oedema peripheral 34/228 (14.9%) 34/226 (15%)
    Pain 10/228 (4.4%) 13/226 (5.8%)
    Pyrexia 28/228 (12.3%) 42/226 (18.6%)
    Injury, poisoning and procedural complications
    Fall 12/228 (5.3%) 4/226 (1.8%)
    Investigations
    Aspartate aminotransferase increased 12/228 (5.3%) 13/226 (5.8%)
    Blood alkaline phosphatase increased 20/228 (8.8%) 6/226 (2.7%)
    Metabolism and nutrition disorders
    Decreased appetite 15/228 (6.6%) 14/226 (6.2%)
    Hypokalaemia 37/228 (16.2%) 30/226 (13.3%)
    Hypomagnesaemia 18/228 (7.9%) 15/226 (6.6%)
    Musculoskeletal and connective tissue disorders
    Back pain 13/228 (5.7%) 12/226 (5.3%)
    Pain in extremity 16/228 (7%) 11/226 (4.9%)
    Nervous system disorders
    Headache 16/228 (7%) 26/226 (11.5%)
    Psychiatric disorders
    Agitation 13/228 (5.7%) 7/226 (3.1%)
    Anxiety 12/228 (5.3%) 15/226 (6.6%)
    Confusional state 10/228 (4.4%) 15/226 (6.6%)
    Hallucination, visual 7/228 (3.1%) 12/226 (5.3%)
    Insomnia 29/228 (12.7%) 22/226 (9.7%)
    Respiratory, thoracic and mediastinal disorders
    Cough 15/228 (6.6%) 22/226 (9.7%)
    Dyspnoea 12/228 (5.3%) 24/226 (10.6%)
    Epistaxis 20/228 (8.8%) 20/226 (8.8%)
    Skin and subcutaneous tissue disorders
    Petechiae 5/228 (2.2%) 12/226 (5.3%)
    Rash 30/228 (13.2%) 31/226 (13.7%)
    Vascular disorders
    Hypertension 32/228 (14%) 21/226 (9.3%)
    Hypotension 30/228 (13.2%) 19/226 (8.4%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer, Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.gov_Inquiries@pfizer.com
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT00531479
    Other Study ID Numbers:
    • A8851009
    First Posted:
    Sep 18, 2007
    Last Update Posted:
    Apr 30, 2012
    Last Verified:
    Apr 1, 2012