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 defence 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 Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study

Study Primary Completion Date: April 2009

Intervention(s) in this Clinical Trial

• Drug: Voriconazole
  • Voriconazole, early treatment
• Drug: Voriconazole
  • 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

• To show whether initiation of voriconazole treatment immediately after onset of fever leads to a lower rate of probable and proven invasive fungal infections as compared to a strategy with initiation of voriconazole treatment only.
  • Time Frame: Day 2-28
    Safety Issue?: No

Secondary Measures

• Time to negative panfungal PCR
  • Time Frame: Day 2-28
    Safety Issue?: No
• Rate of defervescence 96 hours after initiation of study treatment
  • Time Frame: Day 5
    Safety Issue?: No
• Rate of defervescence 192 hours after initiation of study treatment
  • Time Frame: Day 9
    Safety Issue?: No
• Time to defervescence and reasons for lack of defeverescence
  • Time Frame: Day 2-28
    Safety Issue?: No
• Mortality on day 28 after randomization
  • Time Frame: Day 2-28
    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 Sponsor: Pfizer

Overall Clinical Trial Officials and Contacts

Pfizer CT.gov Call Center Study Director Pfizer  

Information obtained from ClinicalTrials.gov on July 02, 2009

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

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