Comparison of Voriconazole and Amphotericin B in Treating Patients With Aspergillosis

Infection Clinical Trial

Official title:

An Open Randomised Comparative Multicentre Study of the Efficacy, Safety and Toleration of Voriconazole Versus Amphotericin-B in the Treatment of Acute Invasive Aspergillosis in Immunocompromised Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003031
• Other study ID #: EORTC-19961
• Secondary ID: EORTC-19961PFIZE
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: June 29, 2012
• Start date: June 1997

Study information

• Verified date: June 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 212
• Est. primary completion date: October 2000
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

DISEASE CHARACTERISTICS: Patient immunocompromised as the result of any of the following:

Allogeneic bone marrow/peripheral stem cell transplant Autologous bone marrow/peripheral stem cell transplant Hematological malignancy (including lymphoma) Aplastic anemia and myelodysplastic syndromes (currently on immunosuppressive treatment) Solid organ transplantation (other than lung) Other solid organ malignancy (after cytotoxic chemotherapy) HIV/AIDS High dose prolonged corticosteroid therapy (at least 20 mg/day of prednisolone or equivalent for more than 3 weeks) or prolonged therapy with other immunosuppressive agents (e.g., azathioprine, methotrexate) Diagnosis of either definite or probable acute invasive aspergillosis Fungal infection represents a new episode of acute invasive aspergillosis Patients with the following are ineligible: Aspergilloma or allergic bronchopulmonary aspergillosis Chronic invasive aspergillosis Sarcoidosis CMV pneumonia

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)

Study Design

Allocation: Randomized, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Aspergillosis
• Infection
• Pulmonary Complications

Intervention

Drug:
• amphotericin B deoxycholate

• voriconazole

Locations

Country	Name	City	State
Australia	Royal Brisbane Hospital	Brisbane	Queensland
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	St. Vincent's Hospital	Sydney	New South Wales
Belgium	Algemeen Ziekenhuis Middelheim	Antwerp
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	Institut Jules Bordet	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
France	CHR de Besancon - Hopital Jean Minjoz	Besancon
France	Centre Hospitalier Universitaire Henri Mondor	Creteil
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 Necker	Paris
France	Hopital Robert Debre	Paris
France	Hopital Saint-Louis	Paris
France	Hotel Dieu de Paris	Paris
France	Hopital Universitaire Hautepierre	Strasbourg
France	CHRU de Nancy - Hopitaux de Brabois	Vandoeuvre-Les-Nancy
Germany	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
Germany	Martin Luther Universitaet	Halle Saale
Germany	Medizinische Hochschule Hannover	Hannover
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	Tubingen
Germany	Klinikum der Universitaet Ulm	Ulm
Hungary	National Institute of Haematology and Immunology	Budapest
Hungary	Szent Laszlo Korhaz	Budapest
Hungary	County Hospital	Kaposvar
Ireland	St. James's Hospital	Dublin
Israel	Hadassah University Hospital	Jerusalem
Italy	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
Luxembourg	Centre Hospitalier de Luxembourg	Luxembourg
Netherlands	Leiden University Medical Center	Leiden
Netherlands	University Medical Center Nijmegen	Nijmegen
Spain	Hospital de Cruces	Barakaldo, Bilbao
Spain	Hospital Clinic y Provincial de Barcelona	Barcelona
Spain	Hospital Del Mar	Barcelona
Spain	Hospital General Gregorio Maranon	Madrid
Spain	Hospital Universitasrio San Carlos	Madrid
Spain	University Hospital - Salamanca	Salamanca
Spain	Hospital Universidad Virgen Del Rocio	Sevilla
Sweden	Huddinge Hospital	Stockholm
Sweden	Karolinska Hospital	Stockholm
Switzerland	University Hospital	Basel
Switzerland	Hopital Cantonal Universitaire de Geneva	Geneva
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Birmingham Heartlands and Solihull NHS Trust (Teaching)	Birmingham	England
United Kingdom	Royal Bournemouth Hospital	Bournemouth
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	North Manchester Healthcare NHS Trust	Manchester
United States	Hartford Medical Group	Wethersfield	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

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