Purpose
Comparison
of Voriconazole and Amphotericin B in Treating Patients With Aspergillosis
This study
is currently recruiting patients.
Sponsored by
EORTC Invasive Fungal
Infections Cooperative Group
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
|
Treatment
or Intervention |
Phase |
pulmonary
complications infection |
Drug: amphotericin
B Drug: voriconazole |
Phase
III |
Study Type: Supportive Care
Official Title: Phase III Randomized Study of the Efficacy,
Safety, and Toleration of Voriconazole vs Amphotericin B in the Treatment of Acute
Invasive Aspergillosis in Immunocompromized Patients
Further Study Details: 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. PROTOCOL OUTLINE: This is an open,
randomized, comparative, multicenter group study. Patients are stratified by center, site
of infection, underlying disease, and baseline neutrophil count. Patients are randomly
assigned to receive voriconazole (Arm I) or amphotericin B (Arm II). Arm I: Patients
receive voriconazole intravenously every 12 hours for 7-28 days, on escalating doses, 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 on either arm may receive
concomitant cyclosporine or tacrolimus. 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 above Criteria
PROTOCOL ENTRY 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 immunosupressive treatment) Solid organ
transplantation Other solid organ malignancy (after cytotoxic chemotherapy) HIV/AIDS High
dose prolonged corticosteroid therapy (greater than 15 mg/day of prednisolone or
equivalent for more than 3 weeks) or prolonged therapy with other immunosupressive 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 --Prior/Concurrent
Therapy-- No systemic treatment with amphotericin B or itraconazole within 8 weeks prior
to study entry No 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 within 2 weeks prior to study entry 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 and phenytoin
No rifampin, rifabutin, or carbamazepine for more than 3 days within 14 days prior to
entry No concurrent investigational drugs other than cytotoxics, antiretroviral agents and
therapies for AIDS-related opportunistic infection No concurrent G-CSF or 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) --Patient Characteristics-- Age: 12
and over Life expectancy: At least 72 hours Hematopoietic: Not specified Hepatic:
Bilirubin no greater than 5 x upper limit of normal (ULN) SGOT/SGPT no greater than 5 x
ULN Alkaline phosphatase no greater than 5 x 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 Effective contraception and negative pregnancy test
at entry required of fertile women 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
Location and Contact Information
New South Wales, Australia
St. Vincent's Hospital, Sydney,
New South Wales, 2010, Australia; Recruiting
Deborah Marriott
02-9361 2083
Queensland, Australia
Royal Brisbane Hospital, Brisbane,
Queensland, 4029, Australia; Recruiting
Anthony Allworth
2538111
Victoria, Australia
Alfred Hospital, Melbourne,
Victoria, 3181, Australia; Recruiting
Jennifer Hoy
03-276-2640
Victoria, Australia
Royal Melbourne Hospital, Parkville,
Victoria, 3050, Australia; Recruiting
Monica Slavin
30-342-7000
Belgium
Algemeen Ziekenhuis
Middelheim, Antwerp, 2020, Belgium; Recruiting
Robrecht De Bock
03-280.31.11
Belgium
Clinique Universitaire De
Mont-Godinne, Mont-Godinne Yvoir, 5530,
Belgium; Recruiting
C. Doyen
32-81-422111
Belgium
Hopital Universitaire
Erasme, Brussels, 1070, Belgium; Recruiting
F. Jacobs
025-55--4433
Belgium
Institut Jules Bordet, Brussels
(Bruxelles), 1000, Belgium; Recruiting
M. Aoun
32-2-541-37-06
Belgium
U.Z. Gasthuisberg, Leuven,
B-3000, Belgium; Recruiting
Marc A. Boogaerts
32-16-346880
Belgium
Universitair Ziekenhuis
Antwerpen, Edegem, B-2650, Belgium; Recruiting
Zwi N. Berneman
+32-(0)3-821-3780
Belgium
Universitair Ziekenhuis Gent, Ghent
(Gent), B-9000, Belgium; Recruiting
Fritz Offner
32-92-40-21-25
France
Centre Hospitalier Universitaire Henri
Mondor, Creteil, 94010, France; Recruiting
Catherine Cordonnier
33-1-49-81-20-59
France
CHR de Besancon - Hopital Jean
Minjoz, Besancon, 25030, France; Recruiting
Jean-Yves Cahn
333-81-66-82-32
France
CHR Hotel Dieu, Nantes,
44093, France; Recruiting
Noel Milpied
33-40-08-32-72
France
CHRU de Nancy - Hopitaux de
Brabois, Vandoeuvre-Les-Nancy, 54511, France; Recruiting
Brigitte Witz
83--15--3274
France
Hopital De L'Institut Pasteur, Paris,
75015, France; Recruiting
Bertrand Dupont
33-1-4568-8196
France
Hopital Du Bocage, Dijon,
21034, France; Recruiting
Denis Caillot
333-80293645
France
Hopital Edouard Herriot, Lyon,
69437, France; Recruiting
Denis Fiere
33-4-72-11-73-99
France
Hopital Necker, Paris,
75743, France; Recruiting
Bruno R. Varet
33-1-44-49-52-82
France
Hopital Robert Debre, Paris,
75019, France; Recruiting
P. Rohrlich
33-1-40032000
France
Hopital Saint-Louis, Paris,
75475, France; Recruiting
Eliane Gluckman
1-42-49-96-44
France
Hopital Universitaire
Hautepierre, Strasbourg, 67098, France; Recruiting
R. Herbrecht
33-388127688
France
Hotel Dieu de Paris, Paris,
75181, France; Recruiting
Robert A. Zittoun
1-42-34-84-13
France
Institut J. Paoli and I.
Calmettes, Marseille, 13273, France; Recruiting
Didier Blaise
33-91-22-33-54
Germany
Eberhard Karls Universitaet, Tubingen,
D-72076, Germany; Recruiting
Hermann Einsele
07071-292711
Germany
Evangelisches Krankenhaus Essen
Werden, Essen, D-45239, Germany; Recruiting
W. Langer +49
201 4089 246
Germany
Klinikum der Universitaet Ulm, Ulm,
D-89081, Germany; Recruiting
Winfried V. Kern
0731-502-4423
Germany
Klinikum Grosshadern, Munich
(Muenchen), D-81377, Germany; Recruiting
Ulrich Jehn
89-7095-2202
Germany
Klinikum Nurnberg, Nuremberg
(Nurnberg), D-90419, Germany; Recruiting
Hannes Wandt
49-911-398-3060
Germany
Klinikum Rechts Der Isar/Technische
Universitaet Muenchen, Munich (Muenchen), D-81675,
Germany; Recruiting
Claudia Wallrauch
089-4140-4110
Germany
Martin Luther Universitaet, Halle
Saale, DOH-0-6112, Germany; Recruiting
Christoph Schober
Germany
Medizinische Hochschule
Hannover, Hannover, D-30625, Germany; Recruiting
Arnold Ganser
0049-511-5323020
Germany
Medizinische Klinik I, Dresden,
D-01307, Germany; Recruiting
Schul
Germany
Staedtische Kliniken
Duisburg, Duisburg, D-47055, Germany; Recruiting
Heinrich H. Gerhartz
03521 7433232
Germany
Stefan Morsch
Stiftung, Idar-Oberstein, D-55743, Germany; Recruiting
Igor Wolfgang Blau
Germany
Universitaetskliniken Bonn, Bonn,
D-53127, Germany; Recruiting
Axel Glasmacher
+49-0228-287-5507
Germany
Universitaetsklinikum Benjamin
Franklin, Berlin, D-12200, Germany; Recruiting
Eckhard Thiel
49-30-8445-2337
Germany
University Medical Center, Freiburg,
D-79106, Germany; Recruiting
R. Mertelsmann
011-49-761-2703406
Germany
Virchow Klinikum Humboldt Universitaet
Berlin, Berlin, D-13353, Germany; Recruiting
Markus Ruhnke
+49-030-4505-9268
Hungary
County Hospital, Kaposvar,
H-7400, Hungary; Recruiting
Miklos Egyed
Hungary
National Institute of Haematology and
Immunology, Budapest, H-1519, Hungary; Recruiting
Karoly Pecze
+13-72--4300
Hungary
Szent Laszlo Korhaz, Budapest,
1097, Hungary; Recruiting
Janos Sinka
36-1-215-3650
Ireland
St. James's Hospital, Dublin,
8, Ireland; Recruiting
Shaun R. McCann
01-353-1-4537941
Israel
Hadassah University
Hospital, Jerusalem, 91120, Israel; Recruiting
Arnon Nagler
415-323-3999
Italy
Istituto Nazionale per la Ricerca sul
Cancro, Genoa (Genova), 16132, Italy; Recruiting
Claudio Viscoli
39-10-5600848/6
Italy
Ospedale Civile Pescara, Pescara,
65100, Italy; Recruiting
Giuseppe Fioritoni
Italy
Ospedale Maggiore Ca Granda, Milano
(Milan), 20162, Italy; Recruiting
Anna-Maria Nosari
02-64442210
Italy
Ospedale San Orsola, Bologna,
40138, Italy; Recruiting
Paolo Ricci
051-6363111
Italy
Policlinico A. Gemelli - Universita
Cattolica del Sacro Cuore, Rome, 00168,
Italy; Recruiting
Livio Pagano
00390630151
Italy
Policlinico Monteluce, Perugia,
06122, Italy; Recruiting
Alibano Del Favero
39-75-5783438
Italy
University and I.R.C.C.S. Policlinico San
Matteo, Pavia, 27100, Italy; Recruiting
Lorenzo Minoli
0382-502580
Luxembourg
Centre Hospitalier de
Luxembourg, Luxembourg, 1210, Luxembourg; Recruiting
Robert Hemmer
352-44113091
Netherlands
Leiden University Medical
Center, Leiden, 2300 ZA, Netherlands; Recruiting
H. Lode
030-80022223
Netherlands
St. Radboud University
Hospital, Nijmegen, 6500 HB, Netherlands; Recruiting
B.E. De Pauw
31 24 3614515
Spain
Hospital Clinic y Provincial de
Barcelona, Barcelona, 08036, Spain; Recruiting
Rovira
34-3-2275511
Spain
Hospital de Cruces, Barakaldo, Bilbao,
E-48903, Spain; Recruiting
A. Aquirrebengo
34 94 6006000
Spain
Hospital Del Mar, Barcelona,
08003, Spain; Recruiting
Saballs
221.10.10
Spain
Hospital General Gregorio
Maranon, Madrid, 28007, Spain; Recruiting
Emilio Bouza
34-1-5868453
Spain
Hospital Universidad Virgen Del
Rocio, Sevilla, 41013, Spain; Recruiting
Cisneros
954248181
Spain
Hospital Universitasrio San
Carlos, Madrid, 28040, Spain; Recruiting
Joaquim Diaz-Mediavilla
34-01-5433834
Spain
University Hospital -
Salamanca, Salamanca, 37007, Spain; Recruiting
Jesus F. San Miguel
923--29-1384
Sweden
Huddinge Hospital, Huddinge,
S-141 86, Sweden; Recruiting
P. Ljungman
468-58580000
Sweden
Karolinska Hospital, Stockholm,
S-171 76, Sweden; Recruiting
J. Magnus Bjorkholm
08-51774198
Switzerland
Centre Hospitalier Universitaire
Vaudois, Lausanne, CH-1011, Switzerland; Recruiting
Jacques Bille
41-21-314-40-57
Switzerland
Hopital Cantonal Universitaire de
Geneva, Geneva, CH-1211, Switzerland; Recruiting
Jorge Garbino
41-22-37-9839
Switzerland
University Hospital, Basel,
CH-4031, Switzerland; Recruiting
A. Gratwohl
011-41-61-265-4277
United Kingdom
North Manchester Healthcare NHS
Trust, Manchester, M8 6RB, United Kingdom; Recruiting
D.W. Denning
0161-720-2734
United Kingdom
Royal Bournemouth
Hospital, Bournemouth, BH7 7DW, United
Kingdom; Recruiting
Han Myint
01202 704790
England, United Kingdom
Addenbrooke's NHS Trust, Cambridge,
England, CB2 2QQ, United Kingdom; Recruiting
Mark Farrington
01223-245151
England, United Kingdom
Birmingham Heartlands and Solihull NHS
Trust (Teaching), Birmingham, England, B9 5SS,
United Kingdom; Recruiting
Dominic Culligan
01224-681818
England, United Kingdom
King's College Hospital, London,
England, SE5 9RS, United Kingdom; Recruiting
Antonio Pagliuca
00 44 020 7346 3709
England, United Kingdom
University College Hospital, London,
England, WC1E 6AU, United Kingdom; Recruiting
Antony H. Goldstone
171 3 87 64 24
Scotland, United Kingdom
Aberdeen Royal Infirmary, Aberdeen,
Scotland, AB25 2ZN, United Kingdom; Recruiting
Dominic Culligan
01224-681818
Connecticut
Hartford Medical Group, Wethersfield,
Connecticut, 06109, United States; Recruiting
A. Aquirrebengo
34 94 6006000
Study chairs or principal investigators
R. Herbrecht, Study Chair
EORTC Invasive Fungal Infections Cooperative
Group
More Information
Study ID Numbers 199/12695;
EORTC-19961; PFIZER-150-307-000
NLM Identifier NCT00003031
Date study started June 1, 1997
Last Updated August 1, 1997