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Comparison of Voriconazole and Amphotericin B in Treating Patients With Aspergillosis

Primary Purpose

Infection, Pulmonary Complications

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
amphotericin B deoxycholate
voriconazole
Sponsored by
European Organisation for Research and Treatment of Cancer - EORTC
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Infection focused on measuring infection, pulmonary complications

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Hartford Medical Group
  • St. Vincent's Hospital
  • Royal Brisbane Hospital
  • Alfred Hospital
  • Royal Melbourne Hospital
  • Algemeen Ziekenhuis Middelheim
  • Institut Jules Bordet
  • Hopital Universitaire Erasme
  • Universitair Ziekenhuis Antwerpen
  • Universitair Ziekenhuis Gent
  • U.Z. Gasthuisberg
  • Clinique Universitaire De Mont-Godinne
  • CHR de Besancon - Hopital Jean Minjoz
  • Centre Hospitalier Universitaire Henri Mondor
  • Hopital Du Bocage
  • Hopital Edouard Herriot
  • Institut J. Paoli and I. Calmettes
  • CHR Hotel Dieu
  • Hopital De L'Institut Pasteur
  • Hopital Robert Debre
  • Hotel Dieu de Paris
  • Hopital Saint-Louis
  • Hopital Necker
  • Hopital Universitaire Hautepierre
  • CHRU de Nancy - Hopitaux de Brabois
  • Universitaetsklinikum Benjamin Franklin
  • Virchow Klinikum Humboldt Universitaet Berlin
  • Universitaetskliniken Bonn
  • Medizinische Klinik I
  • Staedtische Kliniken Duisburg
  • Evangelisches Krankenhaus Essen Werden
  • University Medical Center
  • Martin Luther Universitaet
  • Medizinische Hochschule Hannover
  • Stefan Morsch Stiftung
  • Klinikum Grosshadern
  • Klinikum Rechts Der Isar/Technische Universitaet Muenchen
  • Klinikum Nurnberg
  • Eberhard Karls Universitaet
  • Klinikum der Universitaet Ulm
  • Szent Laszlo Korhaz
  • National Institute of Haematology and Immunology
  • County Hospital
  • St. James's Hospital
  • Hadassah University Hospital
  • Ospedale San Orsola
  • Istituto Nazionale per la Ricerca sul Cancro
  • Ospedale Maggiore Ca Granda
  • University and I.R.C.C.S. Policlinico San Matteo
  • Policlinico Monteluce
  • Ospedale Civile Pescara
  • Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
  • Centre Hospitalier de Luxembourg
  • Leiden University Medical Center
  • University Medical Center Nijmegen
  • Hospital de Cruces
  • Hospital Del Mar
  • Hospital Clinic y Provincial de Barcelona
  • Hospital General Gregorio Maranon
  • Hospital Universitasrio San Carlos
  • University Hospital - Salamanca
  • Hospital Universidad Virgen Del Rocio
  • Huddinge Hospital
  • Karolinska Hospital
  • University Hospital
  • Hopital Cantonal Universitaire de Geneva
  • Centre Hospitalier Universitaire Vaudois
  • Birmingham Heartlands and Solihull NHS Trust (Teaching)
  • Addenbrooke's NHS Trust
  • King's College Hospital
  • University College Hospital
  • Aberdeen Royal Infirmary
  • Royal Bournemouth Hospital
  • North Manchester Healthcare NHS Trust

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
June 29, 2012
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
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1. Study Identification

Unique Protocol Identification Number
NCT00003031
Brief Title
Comparison of Voriconazole and Amphotericin B in Treating Patients With Aspergillosis
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2012
Overall Recruitment Status
Completed
Study Start Date
June 1997 (undefined)
Primary Completion Date
October 2000 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infection, Pulmonary Complications
Keywords
infection, pulmonary complications

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 3
Allocation
Randomized
Enrollment
212 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
amphotericin B deoxycholate
Intervention Type
Drug
Intervention Name(s)
voriconazole

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
R. Herbrecht, MD
Organizational Affiliation
Hopital Universitaire Hautepierre
Official's Role
Study Chair
Facility Information:
Facility Name
Hartford Medical Group
City
Wethersfield
State/Province
Connecticut
ZIP/Postal Code
06109
Country
United States
Facility Name
St. Vincent's Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
Royal Brisbane Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3181
Country
Australia
Facility Name
Royal Melbourne Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Algemeen Ziekenhuis Middelheim
City
Antwerp
ZIP/Postal Code
2020
Country
Belgium
Facility Name
Institut Jules Bordet
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Hopital Universitaire Erasme
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Universitair Ziekenhuis Antwerpen
City
Edegem
ZIP/Postal Code
B-2650
Country
Belgium
Facility Name
Universitair Ziekenhuis Gent
City
Ghent
ZIP/Postal Code
B-9000
Country
Belgium
Facility Name
U.Z. Gasthuisberg
City
Leuven
ZIP/Postal Code
B-3000
Country
Belgium
Facility Name
Clinique Universitaire De Mont-Godinne
City
Mont-Godinne Yvoir
ZIP/Postal Code
5530
Country
Belgium
Facility Name
CHR de Besancon - Hopital Jean Minjoz
City
Besancon
ZIP/Postal Code
25030
Country
France
Facility Name
Centre Hospitalier Universitaire Henri Mondor
City
Creteil
ZIP/Postal Code
94010
Country
France
Facility Name
Hopital Du Bocage
City
Dijon
ZIP/Postal Code
21034
Country
France
Facility Name
Hopital Edouard Herriot
City
Lyon
ZIP/Postal Code
69437
Country
France
Facility Name
Institut J. Paoli and I. Calmettes
City
Marseille
ZIP/Postal Code
13273
Country
France
Facility Name
CHR Hotel Dieu
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Hopital De L'Institut Pasteur
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Hopital Robert Debre
City
Paris
ZIP/Postal Code
75019
Country
France
Facility Name
Hotel Dieu de Paris
City
Paris
ZIP/Postal Code
75181
Country
France
Facility Name
Hopital Saint-Louis
City
Paris
ZIP/Postal Code
75475
Country
France
Facility Name
Hopital Necker
City
Paris
ZIP/Postal Code
75743
Country
France
Facility Name
Hopital Universitaire Hautepierre
City
Strasbourg
ZIP/Postal Code
67098
Country
France
Facility Name
CHRU de Nancy - Hopitaux de Brabois
City
Vandoeuvre-Les-Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
Universitaetsklinikum Benjamin Franklin
City
Berlin
ZIP/Postal Code
D-12200
Country
Germany
Facility Name
Virchow Klinikum Humboldt Universitaet Berlin
City
Berlin
ZIP/Postal Code
D-13353
Country
Germany
Facility Name
Universitaetskliniken Bonn
City
Bonn
ZIP/Postal Code
D-53127
Country
Germany
Facility Name
Medizinische Klinik I
City
Dresden
ZIP/Postal Code
D-01307
Country
Germany
Facility Name
Staedtische Kliniken Duisburg
City
Duisburg
ZIP/Postal Code
D-47055
Country
Germany
Facility Name
Evangelisches Krankenhaus Essen Werden
City
Essen
ZIP/Postal Code
D-45239
Country
Germany
Facility Name
University Medical Center
City
Freiburg
ZIP/Postal Code
D-79106
Country
Germany
Facility Name
Martin Luther Universitaet
City
Halle Saale
ZIP/Postal Code
DOH-0-6112
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
ZIP/Postal Code
D-30625
Country
Germany
Facility Name
Stefan Morsch Stiftung
City
Idar-Oberstein
ZIP/Postal Code
D-55743
Country
Germany
Facility Name
Klinikum Grosshadern
City
Munich
ZIP/Postal Code
D-81377
Country
Germany
Facility Name
Klinikum Rechts Der Isar/Technische Universitaet Muenchen
City
Munich
ZIP/Postal Code
D-81675
Country
Germany
Facility Name
Klinikum Nurnberg
City
Nuremberg (Nurnberg)
ZIP/Postal Code
D-90419
Country
Germany
Facility Name
Eberhard Karls Universitaet
City
Tubingen
ZIP/Postal Code
D-72076
Country
Germany
Facility Name
Klinikum der Universitaet Ulm
City
Ulm
ZIP/Postal Code
D-89081
Country
Germany
Facility Name
Szent Laszlo Korhaz
City
Budapest
ZIP/Postal Code
1097
Country
Hungary
Facility Name
National Institute of Haematology and Immunology
City
Budapest
ZIP/Postal Code
H-1519
Country
Hungary
Facility Name
County Hospital
City
Kaposvar
ZIP/Postal Code
H-7400
Country
Hungary
Facility Name
St. James's Hospital
City
Dublin
ZIP/Postal Code
8
Country
Ireland
Facility Name
Hadassah University Hospital
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Ospedale San Orsola
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Istituto Nazionale per la Ricerca sul Cancro
City
Genoa
ZIP/Postal Code
16132
Country
Italy
Facility Name
Ospedale Maggiore Ca Granda
City
Milan
ZIP/Postal Code
20162
Country
Italy
Facility Name
University and I.R.C.C.S. Policlinico San Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Policlinico Monteluce
City
Perugia
ZIP/Postal Code
06122
Country
Italy
Facility Name
Ospedale Civile Pescara
City
Pescara
ZIP/Postal Code
65100
Country
Italy
Facility Name
Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
City
Rome
ZIP/Postal Code
00168
Country
Italy
Facility Name
Centre Hospitalier de Luxembourg
City
Luxembourg
ZIP/Postal Code
1210
Country
Luxembourg
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2300 ZA
Country
Netherlands
Facility Name
University Medical Center Nijmegen
City
Nijmegen
ZIP/Postal Code
NL-6252 HB
Country
Netherlands
Facility Name
Hospital de Cruces
City
Barakaldo, Bilbao
ZIP/Postal Code
E-48903
Country
Spain
Facility Name
Hospital Del Mar
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Hospital Clinic y Provincial de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital General Gregorio Maranon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hospital Universitasrio San Carlos
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
University Hospital - Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Hospital Universidad Virgen Del Rocio
City
Sevilla
ZIP/Postal Code
E- 41013
Country
Spain
Facility Name
Huddinge Hospital
City
Stockholm
ZIP/Postal Code
S-141 86
Country
Sweden
Facility Name
Karolinska Hospital
City
Stockholm
ZIP/Postal Code
S-171 76
Country
Sweden
Facility Name
University Hospital
City
Basel
ZIP/Postal Code
CH-4031
Country
Switzerland
Facility Name
Hopital Cantonal Universitaire de Geneva
City
Geneva
ZIP/Postal Code
CH-1211
Country
Switzerland
Facility Name
Centre Hospitalier Universitaire Vaudois
City
Lausanne
ZIP/Postal Code
CH-1011
Country
Switzerland
Facility Name
Birmingham Heartlands and Solihull NHS Trust (Teaching)
City
Birmingham
State/Province
England
ZIP/Postal Code
B9 5SS
Country
United Kingdom
Facility Name
Addenbrooke's NHS Trust
City
Cambridge
State/Province
England
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom
Facility Name
King's College Hospital
City
London
State/Province
England
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
University College Hospital
City
London
State/Province
England
ZIP/Postal Code
WC1E 6AU
Country
United Kingdom
Facility Name
Aberdeen Royal Infirmary
City
Aberdeen
State/Province
Scotland
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
Facility Name
Royal Bournemouth Hospital
City
Bournemouth
ZIP/Postal Code
BH7 7DW
Country
United Kingdom
Facility Name
North Manchester Healthcare NHS Trust
City
Manchester
ZIP/Postal Code
M8 6RB
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Comparison of Voriconazole and Amphotericin B in Treating Patients With Aspergillosis

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