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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000992
First received: November 2, 1999
Last updated: March 28, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Histoplasmosis
Drug: Itraconazole
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study to Determine the Feasibility of Itraconazole for Suppression of Relapse of Disseminated Histoplasmosis in Patients With the Acquired Immunodeficiency Syndrome

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 30
Study Completion Date: June 1992
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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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.

Inclusion criteria are:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000992

Locations
United States, California
USC CRS
Los Angeles, California, United States, 90033
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana, United States, 70112
United States, Missouri
Washington U CRS
St. Louis, Missouri, United States
United States, New York
Cornell University A2201
New York, New York, United States, 10021
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 45267
United States, Pennsylvania
Pitt CRS
Pittsburgh, Pennsylvania, United States
Sponsors and Collaborators
Investigators
Study Chair: LJ Wheat
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000992     History of Changes
Other Study ID Numbers: ACTG 084, 11059
Study First Received: November 2, 1999
Last Updated: March 28, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
AIDS-Related Opportunistic Infections
Ketoconazole
Histoplasmosis
Drug Evaluation
Antifungal Agents
Acquired Immunodeficiency Syndrome

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Histoplasmosis
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Mycoses
Itraconazole
Hydroxyitraconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 18, 2014