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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


Phase 3
12 Years
N/A
Not Enrolling
Both
Infection, Pulmonary Complications

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Trial Information

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


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.

Inclusion 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)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Supportive Care

Principal Investigator

R. Herbrecht, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Hopital Universitaire Hautepierre

Authority:

United States: Federal Government

Study ID:

EORTC-19961

NCT ID:

NCT00003031

Start Date:

June 1997

Completion Date:

Related Keywords:

  • Infection
  • Pulmonary Complications
  • infection
  • pulmonary complications
  • Aspergillosis

Name

Location

Hartford Medical GroupWethersfield, Connecticut  06109