- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00150345
Immediate vs. Deferred Empirical Antifungal Treatment With Voriconazole In Neutropenic Patients (IDEA)
Immediate vs. Deferred Empirical Antifungal Treatment With Voriconazole In High-Risk Neutropenic Patients With Fever And A Positive Panfungal Polymerase Chain Reaction Assay (IDEA Study)
A well-known side-effect of cytostatics (drugs against malignancies) is a decrease in the number of white blood cells, especially of the so-called neutrophil granulocytes, which are very important for the defense against infections. Hence their decrease (called "neutropenia") leads to a predisposition to infections.
Since infections during neutropenia can be very dangerous, the patients are treated with antibiotics from the very first signs of such an infection (usually fever). If the antibiotics (drugs against bacteria) do not lead to a normalization of the body temperature within four days, a drug against fungi is added.
In the IDEA study, one half of the patients receive the antifungal drug voriconazole (as usual) only in case the antibiotics alone do not lead to a normalization of the body temperature (current standard of care). The other half of the patients receive voriconazole immediately after onset of fever (concomitantly with the antibiotics).
The research question is, whether in the "early-treatment" group fewer manifest fungal infections will be observed than in the "late-treatment" group.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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-
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Augsburg, Germany, 86156
- Pfizer Investigational Site
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Berlin, Germany, 12200
- Pfizer Investigational Site
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Berlin, Germany, 10117
- Pfizer Investigational Site
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Berlin, Germany, 13353
- Pfizer Investigational Site
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Bielefeld, Germany, 33611
- Pfizer Investigational Site
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Bremen, Germany, 28177
- Pfizer Investigational Site
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Chemnitz, Germany, 09113
- Pfizer Investigational Site
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Dresden, Germany, 01307
- Pfizer Investigational Site
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Erlangen, Germany, 91054
- Pfizer Investigational Site
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Essen, Germany, 45239
- Pfizer Investigational Site
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Frankfurt (Oder), Germany, 15236
- Pfizer Investigational Site
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Freiburg, Germany, 79106
- Pfizer Investigational Site
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Goettingen, Germany, 37075
- Pfizer Investigational Site
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Hannover, Germany, 30623
- Pfizer Investigational Site
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Homburg/Saar, Germany, 66421
- Pfizer Investigational Site
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Kiel, Germany, 24116
- Pfizer Investigational Site
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Koeln, Germany, 50937
- Pfizer Investigational Site
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Leipzig, Germany, 04103
- Pfizer Investigational Site
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Ludwigshafen, Germany, 67063
- Pfizer Investigational Site
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Luebeck, Germany, 23538
- Pfizer Investigational Site
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Mainz, Germany, 55101
- Pfizer Investigational Site
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Muenchen, Germany, 81737
- Pfizer Investigational Site
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Muenchen, Germany, 81675
- Pfizer Investigational Site
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Potsdam, Germany, 14467
- Pfizer Investigational Site
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Stuttgart, Germany, 70376
- Pfizer Investigational Site
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Trier, Germany, 54290
- Pfizer Investigational Site
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Wiesbaden, Germany, 65191
- Pfizer Investigational Site
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Wuerzburg, Germany, 97070
- Pfizer Investigational Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Acute leukemia, aggressive lymphoma, bone marrow or stem cell transplantation;
- Neutropenia (<500 neutrophils/µL) of at least 10 days;
- Newly diagnosed fever;
- Positive panfungal polymerase chain reaction assay
Exclusion Criteria:
- Documented bacterial infection during screening or at randomization
- Fungemia or other documented invasive fungal infection during screening or at randomization.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Early treatment
Voriconazole starts within 18 hours of onset of fever intravenously with a loading dose of 6 mg/kg q12h for the first two doses followed by 4 mg/kg q12h (maintenance dose).
Switched to oral treatment (200 mg BID) is possible after at least four days.
Treatment will be ended if the patient is afebrile (< 38.0 °C) for 7 days with neutrophil counts < 500/µL, or if the patient is afebrile (< 38.0 °C) for 2 days with neutrophil counts > 500/µL.
|
voriconazole, early treatment
voriconazole, deferred treatment
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Other: Deferred treatment
Treatment with voriconazole (for dosage see "early treatment arm") is initiated only if a patient is persistently febrile on day 5 after the onset of fever despite antibiotic treatment.
|
voriconazole, early treatment
voriconazole, deferred treatment
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Proven or Probable Invasive Fungal Infections (IFI): Complete Case Analysis
Time Frame: Day 2 through Day 28
|
Number of participants with proven (deep tissue infection, fungemia, or endemic fungal infections) or probable IFI (at least 1 host criterion [fever, body temperature <36 or >38 degrees Celsius, graft-versus-host disease, use of corticosteroids]; and 1 microbiological criterion [fungal or yeasts]; or clinical criteria [abnormal site consistent with infection]) as defined by European Organization for Research and Treatment of Cancer Mycosis Study Group (EORTC/MSG) criteria.
Complete case analysis: must be evaluable until Day 28 or had developed a proven or probable IFI by the final visit.
|
Day 2 through Day 28
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
Number of participants who achieved defervescence (were afebrile).
Defervescence stated if all of a participants's body temperatures within 24 hours of evaluation time were <38.0 degrees C. Defervescence was not stated and participant was discontinued from the study if participant received antipyretics (non-steroidal anti-inflammatory drugs or paracetamol).
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Day 5 (96 hours through 120 hours after start of study treatment)
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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)
|
Number of participants who achieved defervescence (were afebrile).
Defervescence stated if all of a participant's body temperatures within 24 hours of evaluation time were <38.0 degrees C. Defervescence was not stated and participant was discontinued from the study if participant received antipyretics (non-steroidal anti-inflammatory drugs or paracetamol).
|
Day 9 (192 hours through 216 hours after start of study treatment)
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Time to Continuous Defervescence
Time Frame: Day 2 through Day 28
|
Time (in days) from start of study medication to continuous defervescence.
Continuous defervescence stated if participant maintains a body temperature of <38.0 degrees C for at least 96 hours.
|
Day 2 through Day 28
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Number of Participants Per Reason for Lack of Defervescence
Time Frame: Day 2 through Day 28
|
Day 2 through Day 28
|
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Number of Participants That Died on or Before Day 28 (Mortality)
Time Frame: Day 2 through Day 28
|
Number of participants that died on or before Day 28 after start of study treatment.
A participant must be evaluable until Day 28 (final visit) or have died before the final visit.
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Day 2 through Day 28
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Time to Negative Panfungal Polymerase Chain Reaction (PCR)
Time Frame: Day 2 through Day 28
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Time (in days) from start of study medication to negative panfungal PCR; assessed for participants whose most recent panfungal PCR result prior to start of study medication was positive.
Defined as negative if at least 2 successive and all following panfungal PCR assessments from start of study medication until 24 hours after end of treatment are negative.
Measured as first quartile of time (point in time measurement; no median or measure of dispersion calculated); median time was not estimable for deferred voriconazole treatment group.
|
Day 2 through Day 28
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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
|
Percent of positive panfungal PCR assessments during treatment phase of study in association with achievement of continuous defervescence (response=Yes).
Continuous defervescence stated if participant maintains a body temperature of <38.0 degrees C for at least 96 hours.
Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
|
Day 2 through Day 28
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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
|
Percent of positive panfungal PCR assessments during treatment phase of study in association with achievement of continuous defervescence (response=No).
Continuous defervescence stated if participant maintains a body temperature of <38.0 degrees C for at least 96 hours.
Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
|
Day 2 through Day 28
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Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Age
Time Frame: Day 2 through Day 28
|
Percent of positive panfungal PCR assessments during treatment phase of study in association with age for participants who completed the study and have a non-missing value for percent of positive panfungal PCR.
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Day 2 through Day 28
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Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Gender
Time Frame: Day 2 through Day 28
|
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.
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Day 2 through Day 28
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Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Primary Underlying Neoplastic Disease
Time Frame: Day 2 through Day 28
|
Percent of positive panfungal PCR assessments during treatment phase of study in association with primary underlying neoplastic disease.
Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
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Day 2 through Day 28
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Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Planned Allogeneic Transplants
Time Frame: Day 2 through Day 28
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Percent of positive panfungal PCR assessments during treatment phase of study in association with allogeneic bone marrow transplant or allogeneic peripheral stem cell transplant (Yes or No).
Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
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Day 2 through Day 28
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Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Concomitant Fluconazole
Time Frame: Day 2 through Day 28
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Percent positive panfungal PCR assessments during treatment phase of study in association with use of concomitant (prophylaxis) fluconazole (Yes or No).
Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
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Day 2 through Day 28
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Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Neutrophil Count >500 uL
Time Frame: Day 2 through Day 28
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Percent of positive panfungal PCR assessments during treatment phase of study in association with neutrophil count >500 uL (Yes or No).
Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
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Day 2 through Day 28
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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
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Percent of positive panfungal PCR assessments during treatment phase of study in association with c-reactive protein level (measured in milligrams per liter [mg/L]) >1.25 x ULN (Yes or No).
Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
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Day 2 through Day 28
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Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified
Time Frame: Day 2 through Day 28
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Percent of positive panfungal PCR assessments during treatment phase of study in association with fungal species (singular [one species]=sp; plural [many species]=spp) identified (Yes or No).
Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
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Day 2 through Day 28
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Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified (Aspergillus Spp=Yes)
Time Frame: Day 2 through Day 28
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Percent of positive panfungal PCR assessments during treatment phase of study in association with fungal species (singular [one species]=sp; plural [many species]=spp) identified (Yes).
Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
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Day 2 through Day 28
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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
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Percent of positive panfungal PCR assessments during treatment phase of study in association with proven or probable IFI (complete cases) between Day 2 and Day 28 (Yes or No).
Complete case analysis: participant must be evaluable until Day 28 (final visit) or have developed a proven or probable IFI by the final visit.
Participant considered evaluable until Day 28 if participant completed the study and completed an assessment of IFI at Day 28 or final visit.
Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
|
Day 2 through Day 28
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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)
|
Percent of positive panfungal PCR assessments during treatment phase of study in association with defervescence (were afebrile) Day 5 (Yes or No).
Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
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Day 5 (96 hours through 120 hours after start of study treatment)
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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)
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Percent of positive panfungal PCR assessments during treatment phase of study in association with defervescence (were afebrile) Day 9 (Yes).
Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
|
Day 2 through Day 9 (192 hours through 216 hours after start of study treatment)
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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)
|
Percent of positive panfungal PCR assessments during treatment phase of study in association with defervescence (were afebrile) Day 9 (No).
Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
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Day 2 through Day 9 (192 hours through 216 hours after start of study treatment)
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Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Time to Defervescence
Time Frame: Day 2 through Day 28
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Percent of positive panfungal PCR assessments during treatment phase of study in association with time to defervescence.
Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
|
Day 2 through Day 28
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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
|
Percent of positive panfungal PCR assessments during treatment phase of study in association with lack of continuous defervescence (No).
Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
|
Day 2 through Day 28
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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
|
Percent of positive panfungal PCR assessments during treatment phase of study in association with lack of continuous defervescence (Yes).
Percent calculated as number of positive PCR assessments divided by number of all PCR assessments in treatment phase multiplied by 100.
|
Day 2 through Day 28
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Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Alive)
Time Frame: Day 2 through Day 28
|
Percent of positive panfungal PCR assessments during treatment phase of study in association with mortality on or before Day 28 after start of study treatment (Alive).
A participant must be evaluable until Day 28 (final visit).
|
Day 2 through Day 28
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Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Died)
Time Frame: Day 2 through Day 28
|
Percent of positive panfungal PCR assessments during treatment phase of study in association with mortality on or before Day 28 after start of study treatment (Died).
A participant must have died before Day 28 (final visit).
|
Day 2 through Day 28
|
Number of Participants Assessed as Needing Further Antineoplastic Therapy as Planned
Time Frame: Day 28
|
Day 28
|
|
Number of Participants With Reasons Why Antineoplastic Therapy Not Continued as Planned
Time Frame: Day 28
|
Day 28
|
Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Infections
- Bacterial Infections and Mycoses
- Mycoses
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Hormone Antagonists
- Antifungal Agents
- Steroid Synthesis Inhibitors
- 14-alpha Demethylase Inhibitors
- Voriconazole
Other Study ID Numbers
- A1501029
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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