Pilot Study to Determine the Feasibility of Fluconazole for Induction Treatment and Suppression of Relapse of Histoplasmosis in Patients With the Acquired Immunodeficiency Syndrome

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000627
First received: November 2, 1999
Last updated: March 30, 2012
Last verified: March 2012
  Purpose

To evaluate the use of fluconazole as (1) induction therapy in histoplasmosis, (2) maintenance therapy to prevent relapse of histoplasmosis.

Histoplasmosis is a serious opportunistic infection in patients with AIDS. Fluconazole is a triazole antifungal agent that has been used successfully in the treatment of experimental histoplasmosis in animals, but has not been completely evaluated in patients for this use. It has been approved by the Food and Drug Administration for certain other fungal infections. Nevertheless, physicians are prescribing it to their patients with histoplasmosis. This is a pilot study to examine the role of fluconazole for treating histoplasmosis in AIDS patients.


Condition Intervention
HIV Infections
Histoplasmosis
Drug: Fluconazole

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Primary Purpose: Treatment
Official Title: Pilot Study to Determine the Feasibility of Fluconazole for Induction Treatment and Suppression of Relapse of 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: 90
Study Completion Date: November 1994
Detailed Description:

Histoplasmosis is a serious opportunistic infection in patients with AIDS. Fluconazole is a triazole antifungal agent that has been used successfully in the treatment of experimental histoplasmosis in animals, but has not been completely evaluated in patients for this use. It has been approved by the Food and Drug Administration for certain other fungal infections. Nevertheless, physicians are prescribing it to their patients with histoplasmosis. This is a pilot study to examine the role of fluconazole for treating histoplasmosis in AIDS patients.

At least 40 patients with AIDS and an initial episode of disseminated histoplasmosis are selected for the study. Patients receive fluconazole for a total of 12 weeks. Patients who are unable to take the drug orally may receive it intravenously until oral administration is possible. Patients are evaluated at weeks 0, 1, 2, 4, 8, and 12. Patients who are doing well 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; those who relapse on the reduced dose are permitted to receive re-induction with a higher dose.

  Eligibility

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

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Corticosteroids for up to 21 days at doses no greater than 20 mg/day prednisone (higher doses may be given for shorter durations, if clinically indicated).
  • Zidovudine, oral contraceptives, methadone, narcotics, acyclovir, acetaminophen, sulfonamides, trimethoprim/sulfamethoxazole, pentamidine for Pneumocystis carinii pneumonia (PCP) or PCP prophylaxis, topical antifungals, pyrimethamine, ganciclovir.
  • Didanosine (ddI), dideoxycytidine (ddC), foscarnet, or other investigational drugs considered to be essential for patient management.

Concurrent Treatment:

Allowed:

  • Transfusion.

Patients must have the following:

  • HIV infection.
  • Histoplasmosis.
  • Appropriate consent must be obtained from a parent or legal guardian for patients less than 18 years of age.

Allowed:

  • Hematologic and/or renal laboratory abnormalities.
  • Concurrent malignancies.
  • Concurrent infection with Mycobacteria.
  • Patients with severe manifestations of histoplasmosis who are thought to be at risk of dying within one week should receive up to 250 mg amphotericin B for up to seven days prior to enrollment and then be re-evaluated. Patients who are still severely ill and do not meet eligibility criteria may not enter the study.

Specific criteria defining life-threatening histoplasmosis include:

  • Systolic blood pressure < 90 mm Hg without other cause; arterial pO2 < 60 torr without other cause; and SGOT > 10 x upper limit of normal or bilirubin > 3 x upper limit of normal. Any other cases not meeting this definition must be reviewed with the protocol chair.

Prior Medication:

Allowed:

  • Amphotericin B (up to 250 mg) over 7 days in patients with severe histoplasmosis.

Risk Behavior:

Allowed:

  • Patients with a history of high-risk behavior for HIV infection (bisexual or homosexual men, intravenous drug abusers, recipients of blood or blood products prior to May 1985, or sexual partners of any of the foregoing).

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Allergy to, or intolerance of, imidazoles or azoles.
  • Active hepatitis (viral, drug induced, or other).
  • Fungal infections for which the study drug is not indicated (e.g., aspergillosis, mucormycosis).
  • CNS/CSF culture positive for pathogens other than H. capsulatum. If C. neoformans is subsequently identified and the patient is improving, the patient may be allowed to remain on study with the permission of the protocol chair.

Concurrent Medication:

Excluded:

  • Corticosteroid use for > 21 days at > 20 mg/day of prednisone.
  • Systemic antifungals.

Prior Medication:

Excluded:

  • Amphotericin B at > 2.5 mg/kg for the current episode of histoplasmosis within 7 days prior to enrollment.
  • Suppressive treatment for histoplasmosis or other fungal infections with > 200 mg/day of ketoconazole, fluconazole, or itraconazole, or more than 50 mg amphotericin B twice weekly.

Risk Behavior:

Excluded:

  • Patients who the investigator feels would be undependable with regard to adherence to the protocol.

Patients may not have the following prior conditions:

  • History of allergy to, or intolerance of, imidazoles or azoles.
  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: NCT00000627

Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
San Francisco Veterans Administration Med Ctr
San Francisco, California, United States, 94121
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
Methodist Hosp of Indiana / Life Care Clinic
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Baystate Med Ctr of Springfield
Springfield, Massachusetts, United States, 01199
Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial
Worcester, Massachusetts, United States, 01605
United States, Missouri
Univ of Missouri at Kansas City School of Medicine
Kansas City, Missouri, United States, 641082792
Infectious Diseases Association / Research Med Ctr
Kansas City, Missouri, United States, 64132
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, United States, 63112
United States, New York
Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Montefiore Family Health Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Samaritan Village Inc / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Montefiore Med Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10467
North Central Bronx Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10467
Cornell Univ Med Ctr
New York, New York, United States, 10021
Saint Luke's - Roosevelt Hosp Ctr
New York, New York, United States, 10025
Mount Sinai Med Ctr
New York, New York, United States, 10029
Beth Israel Med Ctr
New York, New York, United States, 10003
United States, Ohio
Ohio State Univ Hosp Clinic
Columbus, Ohio, United States, 432101228
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Texas
Univ TX Health Science Ctr
Houston, Texas, United States, 77030
Houston Veterans Administration Med Ctr
Houston, Texas, United States, 77030
Sponsors and Collaborators
Pfizer
Investigators
Study Chair: Wheat LJ
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000627     History of Changes
Other Study ID Numbers: ACTG 174, R-0245, 11149
Study First Received: November 2, 1999
Last Updated: March 30, 2012
Health Authority: Unspecified

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Pilot Projects
Histoplasmosis
Drug Evaluation
Fluconazole
Acquired Immunodeficiency Syndrome
Recurrence

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
Fluconazole
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 28, 2014