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Comparison of Voriconazole and Amphotericin B in Treating Patients With Aspergillosis
This study is ongoing, but not recruiting participants.
First Received: November 1, 1999   Last Updated: May 9, 2009   History of Changes
Sponsor: European Organization for Research and Treatment of Cancer
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003031
  Purpose

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.


Condition Intervention Phase
Infection
Pulmonary Complications
Drug: amphotericin B deoxycholate
Drug: voriconazole
Phase III

Study Type: Interventional
Study Design: Supportive Care, Randomized
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: 212
Study Start Date: June 1997
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.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003031

  Hide Study Locations
Locations
United States, Connecticut
Hartford Medical Group
Wethersfield, Connecticut, United States, 06109
Australia, New South Wales
St. Vincent's Hospital
Sydney, New South Wales, Australia, 2010
Australia, Queensland
Royal Brisbane Hospital
Brisbane, Queensland, Australia, 4029
Australia, Victoria
Alfred Hospital
Melbourne, Victoria, Australia, 3181
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Belgium
Algemeen Ziekenhuis Middelheim
Antwerp, Belgium, 2020
Clinique Universitaire De Mont-Godinne
Mont-Godinne Yvoir, Belgium, 5530
Hopital Universitaire Erasme
Brussels, Belgium, 1070
Institut Jules Bordet
Brussels, Belgium, 1000
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, B-2650
Universitair Ziekenhuis Gent
Ghent, Belgium, B-9000
France
Centre Hospitalier Universitaire Henri Mondor
Creteil, France, 94010
CHR de Besancon - Hopital Jean Minjoz
Besancon, France, 25030
Hopital Du Bocage
Dijon, France, 21034
CHRU de Nancy - Hopitaux de Brabois
Vandoeuvre-Les-Nancy, France, 54511
Hopital De L'Institut Pasteur
Paris, France, 75015
CHR Hotel Dieu
Nantes, France, 44093
Hopital Edouard Herriot
Lyon, France, 69437
Hopital Necker
Paris, France, 75743
Hopital Robert Debre
Paris, France, 75019
Hopital Saint-Louis
Paris, France, 75475
Institut J. Paoli and I. Calmettes
Marseille, France, 13273
Hotel Dieu de Paris
Paris, France, 75181
Hopital Universitaire Hautepierre
Strasbourg, France, 67098
Germany
Eberhard Karls Universitaet
Tubingen, Germany, D-72076
Evangelisches Krankenhaus Essen Werden
Essen, Germany, D-45239
Klinikum der Universitaet Ulm
Ulm, Germany, D-89081
Universitaetskliniken Bonn
Bonn, Germany, D-53127
Klinikum Nurnberg
Nuremberg (Nurnberg), Germany, D-90419
Klinikum Rechts Der Isar/Technische Universitaet Muenchen
Munich, Germany, D-81675
Martin Luther Universitaet
Halle Saale, Germany, DOH-0-6112
Medizinische Hochschule Hannover
Hannover, Germany, D-30625
Medizinische Klinik I
Dresden, Germany, D-01307
Staedtische Kliniken Duisburg
Duisburg, Germany, D-47055
Stefan Morsch Stiftung
Idar-Oberstein, Germany, D-55743
Klinikum Grosshadern
Munich, Germany, D-81377
Universitaetsklinikum Benjamin Franklin
Berlin, Germany, D-12200
University Medical Center
Freiburg, Germany, D-79106
Virchow Klinikum Humboldt Universitaet Berlin
Berlin, Germany, D-13353
Hungary
County Hospital
Kaposvar, Hungary, H-7400
National Institute of Haematology and Immunology
Budapest, Hungary, H-1519
Szent Laszlo Korhaz
Budapest, Hungary, 1097
Ireland
St. James's Hospital
Dublin, Ireland, 8
Israel
Hadassah University Hospital
Jerusalem, Israel, 91120
Italy
Istituto Nazionale per la Ricerca sul Cancro
Genoa, Italy, 16132
Ospedale Civile Pescara
Pescara, Italy, 65100
Ospedale Maggiore Ca Granda
Milan, Italy, 20162
Ospedale San Orsola
Bologna, Italy, 40138
Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
Rome, Italy, 00168
Policlinico Monteluce
Perugia, Italy, 06122
University and I.R.C.C.S. Policlinico San Matteo
Pavia, Italy, 27100
Luxembourg
Centre Hospitalier de Luxembourg
Luxembourg, Luxembourg, 1210
Netherlands
Leiden University Medical Center
Leiden, Netherlands, 2300 ZA
University Medical Center Nijmegen
Nijmegen, Netherlands, NL-6252 HB
Spain
Hospital Clinic y Provincial de Barcelona
Barcelona, Spain, 08036
Hospital de Cruces
Barakaldo, Bilbao, Spain, E-48903
Hospital Del Mar
Barcelona, Spain, 08003
Hospital General Gregorio Maranon
Madrid, Spain, 28007
Hospital Universidad Virgen Del Rocio
Sevilla, Spain, E- 41013
Hospital Universitasrio San Carlos
Madrid, Spain, 28040
University Hospital - Salamanca
Salamanca, Spain, 37007
Sweden
Huddinge Hospital
Stockholm, Sweden, S-141 86
Karolinska Hospital
Stockholm, Sweden, S-171 76
Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Hopital Cantonal Universitaire de Geneva
Geneva, Switzerland, CH-1211
University Hospital
Basel, Switzerland, CH-4031
United Kingdom
North Manchester Healthcare NHS Trust
Manchester, United Kingdom, M8 6RB
Royal Bournemouth Hospital
Bournemouth, United Kingdom, BH7 7DW
United Kingdom, England
Addenbrooke's NHS Trust
Cambridge, England, United Kingdom, CB2 2QQ
Birmingham Heartlands and Solihull NHS Trust (Teaching)
Birmingham, England, United Kingdom, B9 5SS
King's College Hospital
London, England, United Kingdom, SE5 9RS
University College Hospital
London, England, United Kingdom, WC1E 6AU
United Kingdom, Scotland
Aberdeen Royal Infirmary
Aberdeen, Scotland, United Kingdom, AB25 2ZN
Sponsors and Collaborators
European Organization for Research and Treatment of Cancer
Investigators
Study Chair: R. Herbrecht, MD Hopital Universitaire Hautepierre
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000065627, EORTC-19961, PFIZER-150-307-000
Study First Received: November 1, 1999
Last Updated: May 9, 2009
ClinicalTrials.gov Identifier: NCT00003031     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
infection
pulmonary complications

Additional relevant MeSH terms:
Abelcet
Anti-Infective Agents
Communicable Diseases
Amphotericin B
Antiprotozoal Agents
Gastrointestinal Agents
Aspergillosis
Infection
Liposomal amphotericin B
Pharmacologic Actions
Anti-Bacterial Agents
Mycoses
Antiparasitic Agents
Cholagogues and Choleretics
Antifungal Agents
Therapeutic Uses
Voriconazole
Antibiotics, Antifungal
Deoxycholic Acid
Amphotericin B-deoxycholate
Amebicides

ClinicalTrials.gov processed this record on November 27, 2009