A Study of Itraconazole in Preventing the Return of Histoplasmosis, a Fungal Infection, in Patients With AIDS

NCT ID: NCT00000992

Last Updated: 2021-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 1992-06-30

Brief Summary

To test the effectiveness of itraconazole in preventing the recurrence of disseminated histoplasmosis in AIDS patients.

Histoplasmosis is a serious opportunistic infection in patients with AIDS. Amphotericin B has been used to treat the infection. Although the response to this treatment is generally good, up to 90 percent of AIDS patients who have taken amphotericin B to treat their histoplasmosis infection will have a relapse (that is, they will get the disease again) within 12 months following treatment. Ketoconazole has been used to prevent relapse, but available information suggests that up to 50 percent of AIDS patients relapse even with ketoconazole treatment. A more effective therapy to prevent recurrence is needed. Itraconazole has been used successfully to treat disseminated histoplasmosis in non-AIDS patients and it is hoped that it may be more effective in preventing histoplasmosis relapse.

Detailed Description

Histoplasmosis is a serious opportunistic infection in patients with AIDS. Amphotericin B has been used to treat the infection. Although the response to this treatment is generally good, up to 90 percent of AIDS patients who have taken amphotericin B to treat their histoplasmosis infection will have a relapse (that is, they will get the disease again) within 12 months following treatment. Ketoconazole has been used to prevent relapse, but available information suggests that up to 50 percent of AIDS patients relapse even with ketoconazole treatment. A more effective therapy to prevent recurrence is needed. Itraconazole has been used successfully to treat disseminated histoplasmosis in non-AIDS patients and it is hoped that it may be more effective in preventing histoplasmosis relapse.

AIDS patients who have been successfully treated with amphotericin B for an acute first episode of disseminated histoplasmosis are selected for treatment. They receive daily oral doses of itraconazole for a total of 52 weeks. Patients who do not experience significant toxicity related to the drug may continue to receive itraconazole until the last patient completes 52 weeks of itraconazole therapy or has the study drug discontinued prior to completing 52 weeks of therapy. AMENDED: Patients will be treated for a minimum of 52 weeks. Patients who complete the 52 weeks and remain on the study drug will continue to be followed. If itraconazole becomes licensed for histoplasmosis, study drug must be discontinued at the end of 52 weeks of therapy or at the time of licensure for patients who have received more than 52 weeks of therapy.

Conditions

HIV Infections; Histoplasmosis

Keywords

AIDS-Related Opportunistic Infections; Ketoconazole; Histoplasmosis; Drug Evaluation; Antifungal Agents; Acquired Immunodeficiency Syndrome

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Itraconazole

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Concurrent Medication:

Itraconazole therapy must begin no more than 6 weeks after discontinuing primary amphotericin B therapy; itraconazole therapy may begin immediately after stopping the primary therapy with amphotericin B.

Allowed:

• Oral contraceptives.
• Methadone.
• Narcotics.
• Acyclovir.
• Acetaminophen.
• Sulfonamides.
• Trimethoprim / sulfamethoxazole.
• Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) or PCP prophylaxis (patients with a total CD4+ count < 200 or a history of PCP should receive PCP prophylaxis).
• Treatment IND drugs.
• Zidovudine.
• Topical antifungals.
• Discouraged:
• Antacids.
• Sucralfate.
• H2 blockers.

Concurrent Treatment:

Allowed:

• Radiation therapy for mucocutaneous Kaposi's sarcoma.

Prior Medication:

Required:

• Prior treatment with amphotericin B for disseminated histoplasmosis:
• minimum total dose of 15 mg/kg for patients < 67 kg, or 1 g for patients > 67 kg; must have been administered over 6 months or less.

Allowed:

• Amphotericin B as maintenance therapy for a maximum of 6 weeks following completion of primary therapy.
• Zidovudine.
• Prophylaxis for Pneumocystis carinii pneumonia.

• HIV infection documented by presence of antibody, by ELISA with Western blot confirmation, or serum p24 antigen, or by recovery of HIV in culture.
• Acute first episode of disseminated histoplasmosis documented by recovery and identification of H. capsulatum from cultures obtained from extrapulmonary sites.
• Oriented to person, place, and time, and able to give written informed consent.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions are excluded:

• History of allergy to, or intolerance of, imidazoles or azoles.
• Clinical findings of active histoplasmosis.
• Histoplasmosis of the central nervous system.
• Inability to take oral medications reliably or severe malabsorption syndrome.
• Malignancies requiring cytotoxic therapy.
• Culture-proven systemic Mycobacterium tuberculosis, Mycobacterium avium-intracellulare, coccidioidomycosis, or cryptococcosis.

Concurrent Medication:

Excluded:

• Amphotericin B as maintenance therapy.
• Immunostimulants.
• Ketoconazole.
• Systemic antifungals.
• Steroids in excess of physiologic replacement doses.
• Cytotoxic chemotherapy.
• Investigational agents not specifically allowed.
• Antacids for 4 hours before and 4 hours after itraconazole.

Concurrent Treatment:

Excluded:

• Lymphocyte replacement.

Patients with the following conditions are excluded:

• History of allergy to, or intolerance of, imidazoles or azoles.
• Clinical findings of active histoplasmosis.
• Histoplasmosis of the central nervous system.
• Inability to take oral medications reliably or severe malabsorption syndrome.
• Malignancies requiring cytotoxic therapy.
• Culture-proven systemic Mycobacterium tuberculosis, Mycobacterium avium-intracellulare, coccidioidomycosis, or cryptococcosis.

Prior Medication:

Excluded within 30 days of study entry:

• Immunostimulants.
• Ketoconazole.
• Systemic antifungals.
• Steroids in excess of physiologic replacement doses.
• Cytotoxic chemotherapy.

Prior Treatment:

Excluded:

• Lymphocyte replacement.

Risk Behavior:

Excluded:

• Patients who in the opinion of the investigator would be undependable with regard to adherence to protocol.

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

LJ Wheat

Role: STUDY_CHAIR

Locations

USC CRS

Los Angeles, California, United States

Northwestern University CRS

Chicago, Illinois, United States

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU

New Orleans, Louisiana, United States

Washington U CRS

St Louis, Missouri, United States

Cornell University A2201

New York, New York, United States

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

Pitt CRS

Pittsburgh, Pennsylvania, United States

Countries

United States

References

Wheat J, Hafner R, Wulfsohn M, Spencer P, Squires K, Powderly W, Wong B, Rinaldi M, Saag M, Hamill R, Murphy R, Connolly-Stringfield P, Briggs N, Owens S; National Institute of Allergy and Infectious Diseases Clinical Trials and Mycoses Study Group Collaborators. Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome. Ann Intern Med. 1993 Apr 15;118(8):610-6. doi: 10.7326/0003-4819-118-8-199304150-00006.

Reference Type: BACKGROUND

PMID: 8383934 (View on PubMed)

Other Identifiers

11059

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 084

Identifier Type: -

Identifier Source: org_study_id