Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis

HIV Infections Clinical Trial

Official title: Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis

Status Completed

Clinical Trial Summary

Invasive aspergillosis is a fungal disease which is increasing in incidence with the increase in immunocompromised persons in our population. Persons with prolonged neutropenia secondary to cytotoxic chemotherapies are at the highest risk for acute aspergillosis. Patients undergoing bone marrow transplantation, receiving prolonged corticosteroid or other immunosuppressive therapies, and persons with HIV infection and AIDS are also at risk. Even with antifungal therapy, aspergillosis in its acute invasive forms has a high mortality. In bone marrow transplantation patients and in those whose infection involves the brain, this mortality is greater than 90%. Amphotericin B in its conventional form, is the current standard treatment for this disease. Response to therapy with amphotericin B usually ranges between 20-60% in most studies. The higher response rates are usually seen in those patients who can tolerate this agent for at least 14 days. Because of its nephrotoxicity and other adverse effects, alternatives to conventional amphotericin B have been sought. These currently include liposomal forms of amphotericin B and itraconazole. Although these forms show a decrease in adverse effects, the efficacy of these drugs has not been shown to be equivalent to conventional amphotericin B.

Voriconazole is an investigational antifungal drug currently being brought to phase III trials in the US. This azole has been shown active against Aspergillus spp. in vitro, and in animal models and early human trials to be effective against aspergillosis. It has been shown to be well-tolerated and is available in an intravenous and oral formulation.

This study will evaluate the efficacy, safety, and toleration of voriconazole compared to conventional therapy with amphotericin B as primary treatment of acute invasive aspergillosis in immunocompromised patients. Patients will be randomized to open-labelled therapy with voriconazole or amphotericin B in a one-to-one ratio.

Clinical Trial Description

Invasive aspergillosis is a fungal disease which is increasing in incidence with the increase in immunocompromised persons in our population. Persons with prolonged neutropenia secondary to cytotoxic chemotherapies are at the highest risk for acute aspergillosis. Patients undergoing bone marrow transplantation, receiving prolonged corticosteroid or other immunosuppressive therapies, and persons with HIV infection and AIDS are also at risk. Even with antifungal therapy, aspergillosis in its acute invasive forms has a high mortality. In bone marrow transplantation patients and in those whose infection involves the brain, this mortality is greater than 90%. Amphotericin B, in its conventional form, is the current standard treatment for this disease. Response to therapy with amphotericin B usually ranges between 20-60% in most studies. The higher response rates are usually seen in those patients who can tolerate this agent for at least 14 days. Because of its nephrotoxicity and other adverse effects, alternatives to conventional amphotericin B have been sought. These currently include liposomal forms of amphotericin B and itraconazole. Although these forms show a decrease in adverse effects, the efficacy of these drugs has not been shown to be equivalent to conventional amphotericin B.

Voriconazole is an investigational antifungal drug currently being brought to phase III trials in the U.S. This azole has been shown active against Aspergillus sp. in vitro, and in animal models and early human trials to be effective against aspergillosis. It has been shown to be well-tolerated and is available in an intravenous and oral formulation.

This study will evaluate the efficacy, safety, and toleration of voriconazole compared to conventional therapy with amphotericin B as primary treatment of acute invasive aspergillosis in immunocompromised patients. Although the original protocol allows enrollment of subjects older than 12 years old we do not expect to enroll patients younger than 18 years old. Patients will be randomized to open-labelled therapy with voriconazole or amphotericin B in a one-to-one ratio. ;

Study Design

Endpoint Classification: Efficacy Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Aspergillosis
• HIV Infections
• Immunologic Deficiency Syndromes
• Neutropenia
• Syndrome

• NCT number: NCT00001646
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 3
• Start date: August 1997
• Completion date: August 2000