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
  Purpose

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.


Condition Intervention Phase
Possible Fungal Infection
Drug: voriconazole (Vfend)
Phase 3

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
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With Proven or Probable Invasive Fungal Infections (IFI): Complete Case Analysis [ Time Frame: Day 2 through Day 28 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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).

  • 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) ] [ Designated as safety issue: No ]
    Number of participants who achieved defervescence (were afebrile). Defervescence stated if all of a participant's body temperatures within 24 hours of evaluation time were <38.0 degrees C. Defervescence was not stated and participant was discontinued from the study if participant received antipyretics (non-steroidal anti-inflammatory drugs or paracetamol).

  • Time to Continuous Defervescence [ Time Frame: Day 2 through Day 28 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Per Reason for Lack of Defervescence [ Time Frame: Day 2 through Day 28 ] [ Designated as safety issue: No ]
  • Number of Participants That Died on or Before Day 28 (Mortality) [ Time Frame: Day 2 through Day 28 ] [ Designated as safety issue: No ]
    Number of participants that died on or before Day 28 after start of study treatment. A participant must be evaluable until Day 28 (final visit) or have died before the final visit.

  • Time to Negative Panfungal Polymerase Chain Reaction (PCR) [ Time Frame: Day 2 through Day 28 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Age [ Time Frame: Day 2 through Day 28 ] [ Designated as safety issue: No ]
    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.

  • Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Gender [ Time Frame: Day 2 through Day 28 ] [ Designated as safety issue: No ]
    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.

  • Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Primary Underlying Neoplastic Disease [ Time Frame: Day 2 through Day 28 ] [ Designated as safety issue: No ]
    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.

  • Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Planned Allogeneic Transplants [ Time Frame: Day 2 through Day 28 ] [ Designated as safety issue: No ]
    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.

  • Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Concomitant Fluconazole [ Time Frame: Day 2 through Day 28 ] [ Designated as safety issue: No ]
    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.

  • Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Neutrophil Count >500 uL [ Time Frame: Day 2 through Day 28 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified [ Time Frame: Day 2 through Day 28 ] [ Designated as safety issue: No ]
    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.

  • Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified (Aspergillus Spp=Yes) [ Time Frame: Day 2 through Day 28 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Time to Defervescence [ Time Frame: Day 2 through Day 28 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Alive) [ Time Frame: Day 2 through Day 28 ] [ Designated as safety issue: No ]
    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).

  • Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Died) [ Time Frame: Day 2 through Day 28 ] [ Designated as safety issue: No ]
    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).

  • Number of Participants Assessed as Needing Further Antineoplastic Therapy as Planned [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Number of Participants With Reasons Why Antineoplastic Therapy Not Continued as Planned [ Time Frame: Day 28 ] [ Designated as safety issue: No ]

Enrollment: 147
Study Start Date: January 2005
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: voriconazole (Vfend)
voriconazole, early treatment
Other Name: voriconazole (Vfend)
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.
Drug: voriconazole (Vfend)
voriconazole, deferred treatment
Other Name: voriconazole (Vfend)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00150345

Locations
Germany
Pfizer Investigational Site
Augsburg, Germany, 86156
Pfizer Investigational Site
Berlin, Germany, 12200
Pfizer Investigational Site
Berlin, Germany, 13353
Pfizer Investigational Site
Berlin, Germany, 10117
Pfizer Investigational Site
Bielefeld, Germany, 33611
Pfizer Investigational Site
Bremen, Germany, 28177
Pfizer Investigational Site
Chemnitz, Germany, 09113
Pfizer Investigational Site
Dresden, Germany, 01307
Pfizer Investigational Site
Erlangen, Germany, 91054
Pfizer Investigational Site
Essen, Germany, 45239
Pfizer Investigational Site
Frankfurt (Oder), Germany, 15236
Pfizer Investigational Site
Freiburg, Germany, 79106
Pfizer Investigational Site
Goettingen, Germany, 37075
Pfizer Investigational Site
Hannover, Germany, 30623
Pfizer Investigational Site
Homburg/Saar, Germany, 66421
Pfizer Investigational Site
Kiel, Germany, 24116
Pfizer Investigational Site
Koeln, Germany, 50937
Pfizer Investigational Site
Leipzig, Germany, 04103
Pfizer Investigational Site
Ludwigshafen, Germany, 67063
Pfizer Investigational Site
Luebeck, Germany, 23538
Pfizer Investigational Site
Mainz, Germany, 55101
Pfizer Investigational Site
Muenchen, Germany, 81675
Pfizer Investigational Site
Muenchen, Germany, 81737
Pfizer Investigational Site
Potsdam, Germany, 14467
Pfizer Investigational Site
Stuttgart, Germany, 70376
Pfizer Investigational Site
Trier, Germany, 54290
Pfizer Investigational Site
Wiesbaden, Germany, 65191
Pfizer Investigational Site
Wuerzburg, Germany, 97070
Sponsors and Collaborators
Pfizer
Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
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

Keywords provided by Pfizer:
Neutropenia
Fever of unknown origin
Empirical treatment
Voriconazole

Additional relevant MeSH terms:
Mycoses
Antifungal Agents
Voriconazole
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 08, 2014