Comparison of Voriconazole and Amphotericin B in Treating Patients With Aspergillosis

NCT ID: NCT00003031

Last Updated: 2012-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 212 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-06-30

Brief Summary

RATIONALE: Antifungal therapy with voriconazole or amphotericin B may be an effective treatment for aspergillosis. It is not yet known whether voriconazole is more effective than amphotericin B in treating patients with aspergillosis.

PURPOSE: Randomized phase III trial to compare the effectiveness of voriconazole with amphotericin B in treating patients with aspergillosis.

Detailed Description

OBJECTIVES: I. Compare the efficacy, safety, and toleration of voriconazole versus amphotericin B (CAB) in the treatment of acute invasive aspergillosis in immunocompromised patients. II. Compare the efficacy, safety, and toleration of voriconazole versus CAB followed by other antifungal therapy in the treatment of acute invasive aspergillosis in immunocompromised patients. III. Compare survival in patients treated with voriconazole versus CAB with or without other antifungal therapy. IV. Investigate resource utilization in patients treated with voriconazole versus CAB with or without other antifungal therapy.

OUTLINE: This is an open label, randomized, multicenter study. Patients are stratified according to center, site of infection, underlying disease, and baseline neutrophil count. Patients are randomized to one of two treatment arms. Arm I: Patients receive voriconazole IV every 12 hours for 7-28 days and continue with oral voriconazole twice a day for a maximum total duration of 12 weeks of therapy. Arm II: Patients receive intravenous amphotericin B daily for at least 2 weeks; treatment continues for a maximum of 12 weeks. Patients discontinued from study drug treatment because of toxicity, intolerance or clinical failure may receive alternative (nonstudy) antifungal therapy. All patients are monitored for a total of 16 weeks.

PROJECTED ACCRUAL: A sufficient number of patients will be accrued so that 212 patients (106 per study arm) will be eligible for the study.

Conditions

Infection; Pulmonary Complications

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: SUPPORTIVE_CARE

Interventions

amphotericin B deoxycholate

Intervention Type: DRUG

voriconazole

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

PATIENT CHARACTERISTICS: Age: 12 and over Life expectancy: At least 72 hours Hematopoietic: Not specified Hepatic: Bilirubin no greater than 5 times upper limit of normal (ULN) SGOT/SGPT no greater than 5 times ULN Alkaline phosphatase no greater than 5 times ULN Renal: Creatinine no greater than 2.5 mg/dL Other: No history of hypersensitivity or intolerance to azole antifungal agents including miconazole, ketoconazole, fluconazole, or itraconazole No history of hypersensitivity or severe intolerance to conventional or lipid formulations of amphotericin B Not pregnant or nursing Fertile women must use effective contraception Negative pregnancy test No prior participation on this trial Not on artificial ventilation and unlikely to be extubated within 24 hours No condition that could affect patient safety, preclude evaluation of response, or make study completion unlikely

PRIOR CONCURRENT THERAPY: At least 8 weeks since prior systemic treatment with amphotericin B or itraconazole At least 2 weeks since prior systemic antifungal therapy for more than 96 hours at doses greater than 0.5 mg/kg/day for conventional or lipid formulations of amphotericin B or greater than 200 mg/day of itraconazole No concurrent drugs that are metabolized primarily by hepatic cytochrome P-450 enzymes or which induce or inhibit these enzymes, such as terfenadine, loratidine, astemizole, midazolam, triazolam, cisapride, rifampin, rifabutin, barbiturates, carbamazepine, coumarins, sulfonylureas, nivarapine, erythromycin, ritonavir, delaviridine, omeprazole, and phenytoin At least 2 weeks since prior rifampin, rifabutin, carbamazepine, or barbiturates for more than 3 days No concurrent investigational drugs other than cytotoxics, antiretroviral agents, or therapies for AIDS-related opportunistic infection No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) other than for treatment of granulocytopenia No concurrent white blood cell transfusions No concurrent systemic antifungal agents active against Aspergillus spp. (e.g., itraconazole, lipid formulations of amphotericin B, or flucytosine)

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

R. Herbrecht, MD

Role: STUDY_CHAIR

Hopital Universitaire Hautepierre

Locations

Hartford Medical Group

Wethersfield, Connecticut, United States

St. Vincent's Hospital

Sydney, New South Wales, Australia

Royal Brisbane Hospital

Brisbane, Queensland, Australia

Alfred Hospital

Melbourne, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Algemeen Ziekenhuis Middelheim

Antwerp, , Belgium

Institut Jules Bordet

Brussels, , Belgium

Hopital Universitaire Erasme

Brussels, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

U.Z. Gasthuisberg

Leuven, , Belgium

Clinique Universitaire De Mont-Godinne

Mont-Godinne Yvoir, , Belgium

CHR de Besancon - Hopital Jean Minjoz

Besançon, , France

Centre Hospitalier Universitaire Henri Mondor

Créteil, , France

Hopital Du Bocage

Dijon, , France

Hopital Edouard Herriot

Lyon, , France

Institut J. Paoli and I. Calmettes

Marseille, , France

CHR Hotel Dieu

Nantes, , France

Hopital De L'Institut Pasteur

Paris, , France

Hopital Robert Debre

Paris, , France

Hotel Dieu de Paris

Paris, , France

Hopital Saint-Louis

Paris, , France

Hopital Necker

Paris, , France

Hopital Universitaire Hautepierre

Strasbourg, , France

CHRU de Nancy - Hopitaux de Brabois

Vandœuvre-lès-Nancy, , France

Universitaetsklinikum Benjamin Franklin

Berlin, , Germany

Virchow Klinikum Humboldt Universitaet Berlin

Berlin, , Germany

Universitaetskliniken Bonn

Bonn, , Germany

Medizinische Klinik I

Dresden, , Germany

Staedtische Kliniken Duisburg

Duisburg, , Germany

Evangelisches Krankenhaus Essen Werden

Essen, , Germany

University Medical Center

Freiburg im Breisgau, , Germany

Martin Luther Universitaet

Halle, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Stefan Morsch Stiftung

Idar-Oberstein, , Germany

Klinikum Grosshadern

Munich, , Germany

Klinikum Rechts Der Isar/Technische Universitaet Muenchen

Munich, , Germany

Klinikum Nurnberg

Nuremberg (Nurnberg), , Germany

Eberhard Karls Universitaet

Tübingen, , Germany

Klinikum der Universitaet Ulm

Ulm, , Germany

Szent Laszlo Korhaz

Budapest, , Hungary

National Institute of Haematology and Immunology

Budapest, , Hungary

County Hospital

Kaposvár, , Hungary

St. James's Hospital

Dublin, , Ireland

Hadassah University Hospital

Jerusalem, , Israel

Ospedale San Orsola

Bologna, , Italy

Istituto Nazionale per la Ricerca sul Cancro

Genoa, , Italy

Ospedale Maggiore Ca Granda

Milan, , Italy

University and I.R.C.C.S. Policlinico San Matteo

Pavia, , Italy

Policlinico Monteluce

Perugia, , Italy

Ospedale Civile Pescara

Pescara, , Italy

Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore

Rome, , Italy

Centre Hospitalier de Luxembourg

Luxembourg, , Luxembourg

Leiden University Medical Center

Leiden, , Netherlands

University Medical Center Nijmegen

Nijmegen, , Netherlands

Hospital de Cruces

Barakaldo, Bilbao, , Spain

Hospital Del Mar

Barcelona, , Spain

Hospital Clinic y Provincial de Barcelona

Barcelona, , Spain

Hospital General Gregorio Maranon

Madrid, , Spain

Hospital Universitasrio San Carlos

Madrid, , Spain

University Hospital - Salamanca

Salamanca, , Spain

Hospital Universidad Virgen Del Rocio

Seville, , Spain

Huddinge Hospital

Stockholm, , Sweden

Karolinska Hospital

Stockholm, , Sweden

University Hospital

Basel, , Switzerland

Hopital Cantonal Universitaire de Geneva

Geneva, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Birmingham Heartlands and Solihull NHS Trust (Teaching)

Birmingham, England, United Kingdom

Addenbrooke's NHS Trust

Cambridge, England, United Kingdom

King's College Hospital

London, England, United Kingdom

University College Hospital

London, England, United Kingdom

Aberdeen Royal Infirmary

Aberdeen, Scotland, United Kingdom

Royal Bournemouth Hospital

Bournemouth, , United Kingdom

North Manchester Healthcare NHS Trust

Manchester, , United Kingdom

Countries

United States; Australia; Belgium; France; Germany; Hungary; Ireland; Israel; Italy; Luxembourg; Netherlands; Spain; Sweden; Switzerland; United Kingdom

Other Identifiers

EORTC-19961

Identifier Type: -

Identifier Source: secondary_id

PFIZER-150-307-000

Identifier Type: -

Identifier Source: secondary_id

EORTC-19961

Identifier Type: -

Identifier Source: org_study_id