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

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)”

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.

Intervention(s) in this Clinical Trial

• Drug: voriconazole (Vfend)
  • voriconazole, early treatment
• Drug: voriconazole (Vfend)
  • voriconazole, deferred treatment

Arms, Groups and Cohorts in this Clinical Trial

• 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.
• 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.

Primary Measures

• Number of Participants With Proven or Probable Invasive Fungal Infections (IFI): Complete Case Analysis
  • Time Frame: Day 2 through Day 28
    Safety Issue?: No

Secondary 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)
    Safety Issue?: No
• 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)
    Safety Issue?: No
• Time to Continuous Defervescence
  • Time Frame: Day 2 through Day 28
    Safety Issue?: No
• Number of Participants Per Reason for Lack of Defervescence
  • Time Frame: Day 2 through Day 28
    Safety Issue?: No
• Number of Participants That Died on or Before Day 28 (Mortality)
  • Time Frame: Day 2 through Day 28
    Safety Issue?: No
• Time to Negative Panfungal Polymerase Chain Reaction (PCR)
  • Time Frame: Day 2 through Day 28
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Age
  • Time Frame: Day 2 through Day 28
    Safety Issue?: No
• Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Gender
  • Time Frame: Day 2 through Day 28
    Safety Issue?: No
• Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Primary Underlying Neoplastic Disease
  • Time Frame: Day 2 through Day 28
    Safety Issue?: No
• Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Planned Allogeneic Transplants
  • Time Frame: Day 2 through Day 28
    Safety Issue?: No
• Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Concomitant Fluconazole
  • Time Frame: Day 2 through Day 28
    Safety Issue?: No
• Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Neutrophil Count >500 uL
  • Time Frame: Day 2 through Day 28
    Safety Issue?: No
• 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
    Safety Issue?: No
• Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified
  • Time Frame: Day 2 through Day 28
    Safety Issue?: No
• Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Fungal Species Identified (Aspergillus Spp=Yes)
  • Time Frame: Day 2 through Day 28
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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)
    Safety Issue?: No
• 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)
    Safety Issue?: No
• Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Time to Defervescence
  • Time Frame: Day 2 through Day 28
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Alive)
  • Time Frame: Day 2 through Day 28
    Safety Issue?: No
• Course of Positive Panfungal PCR Assessments to Explanatory Variables: Association With Mortality by Day 28 (Died)
  • Time Frame: Day 2 through Day 28
    Safety Issue?: No
• Number of Participants Assessed as Needing Further Antineoplastic Therapy as Planned
  • Time Frame: Day 28
    Safety Issue?: No
• Number of Participants With Reasons Why Antineoplastic Therapy Not Continued as Planned
  • Time Frame: Day 28
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Pfizer Industry

Overall Clinical Trial Officials and Contacts

Pfizer CT.gov Call Center Study Director Pfizer  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00150345

Study ID Number: A1501029

ClinicalTrials.gov Identifier: NCT00150345

Health Authority: Germany: Federal Institute for Drugs and Medical Devices

To obtain contact information for a study center near you, click here.