Comparison of Voriconazole and Amphotericin B in Treating Patients With Aspergillosis

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Completed

CT.gov ID

NCT00003031

Collaborator

(none)

212

Enrollment

Locations

2.9

Patients Per Site

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Infection Pulmonary Complications	Drug: amphotericin B deoxycholate Drug: voriconazole	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

212 participants

Allocation:

Randomized

Primary Purpose:

Supportive Care

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 Start Date :

Jun 1, 1997

Actual Primary Completion Date :

Oct 1, 2000

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hartford Medical Group	Wethersfield	Connecticut	United States	06109
2	St. Vincent's Hospital	Sydney	New South Wales	Australia	2010
3	Royal Brisbane Hospital	Brisbane	Queensland	Australia	4029
4	Alfred Hospital	Melbourne	Victoria	Australia	3181
5	Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
6	Algemeen Ziekenhuis Middelheim	Antwerp		Belgium	2020
7	Institut Jules Bordet	Brussels		Belgium	1000
8	Hopital Universitaire Erasme	Brussels		Belgium	1070
9	Universitair Ziekenhuis Antwerpen	Edegem		Belgium	B-2650
10	Universitair Ziekenhuis Gent	Ghent		Belgium	B-9000
11	U.Z. Gasthuisberg	Leuven		Belgium	B-3000
12	Clinique Universitaire De Mont-Godinne	Mont-Godinne Yvoir		Belgium	5530
13	CHR de Besancon - Hopital Jean Minjoz	Besancon		France	25030
14	Centre Hospitalier Universitaire Henri Mondor	Creteil		France	94010
15	Hopital Du Bocage	Dijon		France	21034
16	Hopital Edouard Herriot	Lyon		France	69437
17	Institut J. Paoli and I. Calmettes	Marseille		France	13273
18	CHR Hotel Dieu	Nantes		France	44093
19	Hopital De L'Institut Pasteur	Paris		France	75015
20	Hopital Robert Debre	Paris		France	75019
21	Hotel Dieu de Paris	Paris		France	75181
22	Hopital Saint-Louis	Paris		France	75475
23	Hopital Necker	Paris		France	75743
24	Hopital Universitaire Hautepierre	Strasbourg		France	67098
25	CHRU de Nancy - Hopitaux de Brabois	Vandoeuvre-Les-Nancy		France	54511
26	Universitaetsklinikum Benjamin Franklin	Berlin		Germany	D-12200
27	Virchow Klinikum Humboldt Universitaet Berlin	Berlin		Germany	D-13353
28	Universitaetskliniken Bonn	Bonn		Germany	D-53127
29	Medizinische Klinik I	Dresden		Germany	D-01307
30	Staedtische Kliniken Duisburg	Duisburg		Germany	D-47055
31	Evangelisches Krankenhaus Essen Werden	Essen		Germany	D-45239
32	University Medical Center	Freiburg		Germany	D-79106
33	Martin Luther Universitaet	Halle Saale		Germany	DOH-0-6112
34	Medizinische Hochschule Hannover	Hannover		Germany	D-30625
35	Stefan Morsch Stiftung	Idar-Oberstein		Germany	D-55743
36	Klinikum Grosshadern	Munich		Germany	D-81377
37	Klinikum Rechts Der Isar/Technische Universitaet Muenchen	Munich		Germany	D-81675
38	Klinikum Nurnberg	Nuremberg (Nurnberg)		Germany	D-90419
39	Eberhard Karls Universitaet	Tubingen		Germany	D-72076
40	Klinikum der Universitaet Ulm	Ulm		Germany	D-89081
41	Szent Laszlo Korhaz	Budapest		Hungary	1097
42	National Institute of Haematology and Immunology	Budapest		Hungary	H-1519
43	County Hospital	Kaposvar		Hungary	H-7400
44	St. James's Hospital	Dublin		Ireland	8
45	Hadassah University Hospital	Jerusalem		Israel	91120
46	Ospedale San Orsola	Bologna		Italy	40138
47	Istituto Nazionale per la Ricerca sul Cancro	Genoa		Italy	16132
48	Ospedale Maggiore Ca Granda	Milan		Italy	20162
49	University and I.R.C.C.S. Policlinico San Matteo	Pavia		Italy	27100
50	Policlinico Monteluce	Perugia		Italy	06122
51	Ospedale Civile Pescara	Pescara		Italy	65100
52	Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore	Rome		Italy	00168
53	Centre Hospitalier de Luxembourg	Luxembourg		Luxembourg	1210
54	Leiden University Medical Center	Leiden		Netherlands	2300 ZA
55	University Medical Center Nijmegen	Nijmegen		Netherlands	NL-6252 HB
56	Hospital de Cruces	Barakaldo, Bilbao		Spain	E-48903
57	Hospital Del Mar	Barcelona		Spain	08003
58	Hospital Clinic y Provincial de Barcelona	Barcelona		Spain	08036
59	Hospital General Gregorio Maranon	Madrid		Spain	28007
60	Hospital Universitasrio San Carlos	Madrid		Spain	28040
61	University Hospital - Salamanca	Salamanca		Spain	37007
62	Hospital Universidad Virgen Del Rocio	Sevilla		Spain	E- 41013
63	Huddinge Hospital	Stockholm		Sweden	S-141 86
64	Karolinska Hospital	Stockholm		Sweden	S-171 76
65	University Hospital	Basel		Switzerland	CH-4031
66	Hopital Cantonal Universitaire de Geneva	Geneva		Switzerland	CH-1211
67	Centre Hospitalier Universitaire Vaudois	Lausanne		Switzerland	CH-1011
68	Birmingham Heartlands and Solihull NHS Trust (Teaching)	Birmingham	England	United Kingdom	B9 5SS
69	Addenbrooke's NHS Trust	Cambridge	England	United Kingdom	CB2 2QQ
70	King's College Hospital	London	England	United Kingdom	SE5 9RS
71	University College Hospital	London	England	United Kingdom	WC1E 6AU
72	Aberdeen Royal Infirmary	Aberdeen	Scotland	United Kingdom	AB25 2ZN
73	Royal Bournemouth Hospital	Bournemouth		United Kingdom	BH7 7DW
74	North Manchester Healthcare NHS Trust	Manchester		United Kingdom	M8 6RB