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Immediate vs. Deferred Empirical Antifungal Treatment With Voriconazole In Neutropenic Patients (IDEA)

This study has been completed.
Sponsor:
Collaborator:
Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00150345
First received: September 6, 2005
Last updated: January 17, 2012
Last verified: January 2012
History of Changes
Results First Received: April 5, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Possible Fungal Infection
Intervention: Drug: voriconazole (Vfend)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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).

Reporting Groups
  Description
Immediate Voriconazole 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.
Deferred Voriconazole Treatment 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.

Participant Flow:   Overall Study
    Immediate Voriconazole     Deferred Voriconazole Treatment  
STARTED     81     66  
COMPLETED     47     34  
NOT COMPLETED     34     32  
Death                 5                 2  
Adverse Event                 8                 6  
Lack of Efficacy                 5                 4  
Withdrawal by Subject                 3                 4  
Laboratory abnormality                 1                 2  
Unspecified                 12                 14  



  Baseline Characteristics
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Reporting Groups
  Description
Immediate Voriconazole 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.
Deferred Voriconazole Treatment 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 Total of all reporting groups

Baseline Measures
    Immediate Voriconazole     Deferred Voriconazole Treatment     Total  
Number of Participants  
[units: participants]
 		  81     66     147  
Age, Customized  
[units: participants]
 		     
Between 18 and 44 years     29     17     46  
Between 45 and 64 years     31     35     66  
>=65 years     21     14     35  
Gender  
[units: participants]
 		     
Female     39     29     68  
Male     42     37     79  
Race/Ethnicity, Customized  
[units: participants]
 		     
White     81     65     146  
Other     0     1     1  
Weight  
[units: kilograms (kg)]
Mean ( Full Range ) 		  77.1  
  ( 42.0 to 112.5 )   		  79.2  
  ( 45.3 to 152.0 )   		  78.1  
  ( 42.0 to 152.0 )  
Height  
[units: centimeters (cm)]
Mean ( Full Range ) 		  172.1  
  ( 150.0 to 196.0 )   		  171.9  
  ( 153.0 to 198.0 )   		  172.0  
  ( 150.0 to 198.0 )  



  Outcome Measures
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1.  Primary:   Number of Participants With Proven or Probable Invasive Fungal Infections (IFI): Complete Case Analysis   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 1

2.  Secondary:   Number of Participants With Defervescence Day 5 (4 Days After Initiation of Study Treatment)   [ Time Frame: Day 5 (96 hours through 120 hours after start of study treatment) ]
  Show Outcome Measure 2

3.  Secondary:   Number of Participants With Defervescence Day 9 (8 Days After Initiation of Study Treatment)   [ Time Frame: Day 9 (192 hours through 216 hours after start of study treatment) ]
  Show Outcome Measure 3

4.  Secondary:   Time to Continuous Defervescence   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 4

5.  Secondary:   Number of Participants Per Reason for Lack of Defervescence   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 5

6.  Secondary:   Number of Participants That Died on or Before Day 28 (Mortality)   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 6

7.  Secondary:   Time to Negative Panfungal Polymerase Chain Reaction (PCR)   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 7

8.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association of Positive PCR Assessments With Achievement of Continuous Defervescence (Yes)   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 8

9.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association of Positive PCR Assessments With Achievement of Continuous Defervescence (No)   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 9

10.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Age   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 10

11.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Gender   [ Time Frame: Day 2 through Day 28 ]
  Hide Outcome Measure 11

Measure Type Secondary
Measure Title Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Gender
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Immediate Voriconazole 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.
Deferred Voriconazole Treatment 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.

Measured Values
    Immediate Voriconazole     Deferred Voriconazole Treatment  
Number of Participants Analyzed  
[units: participants]
 		  68     54  
Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Gender  
[units: percent of positive PCR assessments]
Mean ± Standard Deviation 		   
Female (n=21, 12)     12.3  ± 14.82     4.2  ± 10.36  
Male (n=18, 15)     10.4  ± 14.75     11.1  ± 17.16  

No statistical analysis provided for Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Gender



12.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Primary Underlying Neoplastic Disease   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 12

13.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Planned Allogeneic Transplants   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 13

14.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Concomitant Fluconazole   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 14

15.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Neutrophil Count >500 uL   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 15

16.  Secondary:   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)   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 16

17.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 17

18.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified (Aspergillus Spp=Yes)   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 18

19.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Proven or Probable IFI (Complete Cases) Between Day 2 and Day 28   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 19

20.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence Day 5 (4 Days After Initiation of Study Treatment)   [ Time Frame: Day 5 (96 hours through 120 hours after start of study treatment) ]
  Show Outcome Measure 20

21.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence (Yes) by Day 9 (8 Days After Initiation of Study Treatment)   [ Time Frame: Day 2 through Day 9 (192 hours through 216 hours after start of study treatment) ]
  Show Outcome Measure 21

22.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Defervescence (No) by Day 9 (8 Days After Initiation of Study Treatment)   [ Time Frame: Day 2 through Day 9 (192 hours through 216 hours after start of study treatment) ]
  Show Outcome Measure 22

23.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Time to Defervescence   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 23

24.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence (No)   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 24

25.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Reasons for Lack of Continuous Defervescence: Unknown Infection (Yes)   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 25

26.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Alive)   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 26

27.  Secondary:   Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Died)   [ Time Frame: Day 2 through Day 28 ]
  Show Outcome Measure 27

28.  Secondary:   Number of Participants Assessed as Needing Further Antineoplastic Therapy as Planned   [ Time Frame: Day 28 ]
  Show Outcome Measure 28

29.  Secondary:   Number of Participants With Reasons Why Antineoplastic Therapy Not Continued as Planned   [ Time Frame: Day 28 ]
  Show Outcome Measure 29


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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).  


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.govCallCenter@pfizer.com


No publications provided


Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00150345     History of Changes
Other Study ID Numbers: A1501029
Study First Received: September 6, 2005
Results First Received: April 5, 2010
Last Updated: January 17, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices