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

NCT00150345 | Completed Phase 3 Results

• 1 other identifier: A1501029
• Study Type: interventional
• Target: 147
• Locations: 1 country
• Sites: 28

Brief Summary

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.

Conditions

Possible Fungal Infection

Keywords

Neutropenia; Fever of unknown origin; Empirical treatment; Voriconazole

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Proven or Probable Invasive Fungal Infections (IFI): Complete Case Analysis

  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 Outcomes (28)

• Number of Participants With Defervescence Day 5 (4 Days After Initiation of Study Treatment)

  Day 5 (96 hours through 120 hours after start of study treatment)

• Number of Participants With Defervescence Day 9 (8 Days After Initiation of Study Treatment)

  Day 9 (192 hours through 216 hours after start of study treatment)

• Time to Continuous Defervescence

  Day 2 through Day 28

• Number of Participants Per Reason for Lack of Defervescence

  Day 2 through Day 28

• Number of Participants That Died on or Before Day 28 (Mortality)

  Day 2 through Day 28

Study Arms (2)

Early treatment

EXPERIMENTAL

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)

Deferred treatment

OTHER

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)

Interventions

voriconazole (Vfend) DRUG

voriconazole, early treatment

Early treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Documented bacterial infection during screening or at randomization
• Fungemia or other documented invasive fungal infection during screening or at randomization.

Sponsors & Collaborators

• Pfizer: lead
• Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO): collaborator

Study Sites (28)

Pfizer Investigational Site

Augsburg, 86156, Germany

Location

Pfizer Investigational Site

Berlin, 10117, Germany

Location

Pfizer Investigational Site

Berlin, 12200, Germany

Location

Pfizer Investigational Site

Berlin, 13353, Germany

Location

Pfizer Investigational Site

Bielefeld, 33611, Germany

Location

Pfizer Investigational Site

Bremen, 28177, Germany

Location

Pfizer Investigational Site

Chemnitz, 09113, Germany

Location

Pfizer Investigational Site

Cologne, 50937, Germany

Location

Pfizer Investigational Site

Dresden, 01307, Germany

Location

Pfizer Investigational Site

Erlangen, 91054, Germany

Location

Pfizer Investigational Site

Essen, 45239, Germany

Location

Pfizer Investigational Site

Frankfurt (Oder), 15236, Germany

Location

Pfizer Investigational Site

Freiburg im Breisgau, 79106, Germany

Location

Pfizer Investigational Site

Göttingen, 37075, Germany

Location

Pfizer Investigational Site

Hanover, 30623, Germany

Location

Pfizer Investigational Site

Homburg/Saar, 66421, Germany

Location

Pfizer Investigational Site

Kiel, 24116, Germany

Location

Pfizer Investigational Site

Leipzig, 04103, Germany

Location

Pfizer Investigational Site

Ludwigshafen, 67063, Germany

Location

Pfizer Investigational Site

Lübeck, 23538, Germany

Location

Pfizer Investigational Site

Mainz, 55101, Germany

Location

Pfizer Investigational Site

München, 81675, Germany

Location

Pfizer Investigational Site

München, 81737, Germany

Location

Pfizer Investigational Site

Potsdam, 14467, Germany

Location

Pfizer Investigational Site

Stuttgart, 70376, Germany

Location

Pfizer Investigational Site

Trier, 54290, Germany

Location

Pfizer Investigational Site

Wiesbaden, 65191, Germany

Location

Pfizer Investigational Site

Würzburg, 97070, Germany

Location

Related Links

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

MeSH Terms

Conditions

Neutropenia; Fever of Unknown Origin

Interventions

Voriconazole

Condition Hierarchy (Ancestors)

Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Fever; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

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

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.govCallCenter@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2005
• First Posted: September 8, 2005
• Study Start: January 1, 2005
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: January 19, 2012
• Results First Posted: August 18, 2010

Record last verified: 2012-01

Locations

DE (28)