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Clinical Trials

MainTitle

A Study of Itraconazole in the Treatment and Prevention of Histoplasmosis, a Fungal Infection, in Patients With AIDS

This study has been completed
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator
Janssen Pharmaceuticals

Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier
NCT00000975

First received: November 2, 1999
Last updated: March 28, 2012
Last Verified: March 2012
History of Changes
Purpose

Purpose

To evaluate the feasibility of itraconazole as (1) primary therapy in histoplasmosis and (2) maintenance therapy after completion of primary therapy. To evaluate the effect of therapy of CNS histoplasmosis. To determine if resistance to drug occurs in patients who fail therapy.

Histoplasmosis is a serious opportunistic infection in patients with AIDS. Although the clinical response to amphotericin B treatment in the AIDS patients is generally good, administration difficulties and toxicity detract from its usefulness. Oral treatment with ketoconazole overcomes these limitations of amphotericin B, but does not appear to be effective for primary treatment in patients with AIDS. Itraconazole is a triazole compound in which preclinical studies have demonstrated activity against Histoplasmosis capsulatum. Preclinical studies have also shown that itraconazole appears effective in the treatment of histoplasmosis. The frequency of adverse reactions to itraconazole has been low in several studies. Central nervous system (CNS) involvement occurs in up to 20 percent of patients with histoplasmosis, and appears to have a poor response to amphotericin B treatment. Itraconazole has been used successfully in a small number of patients with cryptococcal meningitis, supporting a study of its use in CNS histoplasmosis.

Condition Intervention Phase
HIV Infections
Histoplasmosis

Drug : Itraconazole
Phase 2

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

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

Enrollment: 30
Study Completion Date: September 1994

Detailed Description:

Histoplasmosis is a serious opportunistic infection in patients with AIDS. Although the clinical response to amphotericin B treatment in the AIDS patients is generally good, administration difficulties and toxicity detract from its usefulness. Oral treatment with ketoconazole overcomes these limitations of amphotericin B, but does not appear to be effective for primary treatment in patients with AIDS. Itraconazole is a triazole compound in which preclinical studies have demonstrated activity against Histoplasmosis capsulatum. Preclinical studies have also shown that itraconazole appears effective in the treatment of histoplasmosis. The frequency of adverse reactions to itraconazole has been low in several studies. Central nervous system (CNS) involvement occurs in up to 20 percent of patients with histoplasmosis, and appears to have a poor response to amphotericin B treatment. Itraconazole has been used successfully in a small number of patients with cryptococcal meningitis, supporting a study of its use in CNS histoplasmosis.
At least 30 patients with AIDS and an initial episode of disseminated histoplasmosis are selected for this study. Up to 5 patients will have a diagnosis of CNS histoplasmosis. Therapy with all other systemic antifungal agents must be halted before study entry. Patients receive itraconazole for 3 days followed by daily oral doses for a total of 12 weeks. Patients who are doing well clinically, without evidence of clinical failure or dose-limiting toxicity, are permitted to continue maintenance therapy to prevent relapse at a reduced dose for an additional 12 months. Patients who are being treated for CNS histoplasmosis will continue to receive itraconazole.

Eligibility

Eligibility

Ages Eligible for Study: 13 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria
Concurrent Medication:
Allowed:

  • Vincristine, vinblastine, bleomycin, or interferon for Kaposi's sarcoma.
  • Erythropoietin.
  • Didanosine by exemption for 10 patients.
  • Barbiturates.
  • Coumarin-type anticoagulants.
  • Oral contraceptives.
  • Digoxin.
  • Methadone.
  • Narcotics.
  • Acyclovir.
  • Acetaminophen.
  • Sulfonamides.
  • Trimethoprim / sulfamethoxazole.
  • Pentamidine for Pneumocystis carinii pneumonia (PCP) or PCP prophylaxis.
  • Topical antifungals.
  • Pyrimethamine.
  • Ganciclovir.
  • AZT.
  • Stress doses of steroids in patients with adrenal insufficiency.

  • Concurrent Treatment:
    Allowed:
  • Dose reduction or interruption of myelosuppressive therapy and transfusion to maintain hemoglobin of 7 or more g/dl.
  • Radiation therapy.

  • Patient must:
  • Show laboratory evidence of HIV infection and disseminated histoplasmosis.
  • Be oriented to person, place, and time.
  • Be able to give written informed consent (appropriate consent must be obtained from a parent or legal guardian for patients under 18 years of age).

  • Allowed:
  • Abnormal liver function tests in Grade 3 toxicity range if liver biopsy shows evidence that histoplasmosis caused these abnormalities.
  • Mucocutaneous candidiasis.

  • Prior Medication:
    Allowed:
  • Amphotericin B or ketoconazole for pulmonary histoplasmosis at least 3 months prior to study entry.
  • Azidothymidine (AZT).
  • Vincristine, vinblastine, bleomycin, or interferon for mucocutaneous Kaposi's sarcoma.
  • Prophylaxis for Pneumocystis carinii pneumonia (PCP).

  • Exclusion Criteria
    Co-existing Condition:
    Patients with the following conditions or symptoms are excluded:
  • Severely ill, or at risk of dying from histoplasmosis within the first week of treatment, as indicated by systolic blood pressure less than 90 mm Hg , or PO2 less than 60.
  • Active CNS lesions, malignancies, or infections other than MAI.
  • Severe malabsorption syndrome (persistent diarrhea more than 4 weeks duration with at least 4 loose stools per day accompanied by a 10 percent or greater weight loss).
  • Requiring cytotoxic therapy for malignancies.
  • Any systemic fungal infection other than histoplasmosis.
  • Systemic Mycobacterium avium intracellulare.
  • Receiving treatment for other acute opportunistic infections whose signs and symptoms have not yet resolved or stabilized.
  • History of allergy to or intolerance of imidazoles or azoles.

  • Concurrent Medication:
    Excluded:
  • All other systemic antifungal agents.
  • Investigational drugs not specifically allowed.
  • Oral hypoglycemics.
  • Rifamycins.
  • Phenytoin.
  • Carbamazepine.
  • Steroids in excess of physiologic replacement doses not specifically allowed.
  • Cytotoxic chemotherapy.
  • Discouraged:
  • Antacids.
  • Sucralfate.
  • H2 blockers.

  • Patients with the following are excluded:
  • Severely ill, or at risk of dying from histoplasmosis within the first week of treatment.
  • Active CNS infections, malignancies or lesions not documented to be caused by histoplasmosis, which would interfere with assessment of response.
  • Unable to take oral medications reliably.
  • Severe malabsorption syndrome.
  • Requiring cytotoxic therapy for malignancies.
  • Any systemic fungal infection other than histoplasmosis.
  • Systemic Mycobacterium avium intracellulare.
  • Receiving treatment for other acute opportunistic infections whose signs and symptoms have not yet resolved or stabilized.

  • Prior Medication:
    Excluded for greater than 1 week within the last 3 months:
  • Fluconazole.
  • Itraconazole.
  • SCH 39304.
  • Amphotericin B greater than 1.5 mg/kg, or any other antifungal for this episode of
disseminated histoplasmosis.
Patients who the investigator feels would be undependable with regard to adherence to the protocol.

contacts and locations

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: NCT00000975

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, Minnesota
University of Minnesota, ACTU
Minneapolis, Minnesota, United States, 55455
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
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
United States, North Carolina
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, United States, 27710
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 45267
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States
United States, Pennsylvania
Pitt CRS
Pittsburgh, Pennsylvania, United States

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
Janssen Pharmaceuticals

Investigators

Study Chair: LJ Wheat
More Information

More Information


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)  
ClinicalTrials.gov Identifier: NCT00000975   History of Changes  
Other Study ID Numbers: ACTG 120  
  11095  
Study First Received: November 2, 1999  
Last Updated: March 28, 2012  

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

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

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
Histoplasmosis
Itraconazole
Hydroxyitraconazole

ClinicalTrials.gov processed this data on October 18, 2017
This information is provided by ClinicalTrials.gov.