Pilot Study to Determine the Feasibility of Fluconazole for Induction Treatment and Suppression of Relapse of Histoplasmosis in Patients With the Acquired Immunodeficiency Syndrome
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections; Histoplasmosis
Intervention: Fluconazole (Drug)
Phase: N/A
Status: Completed
Sponsored by: Pfizer Official(s) and/or principal investigator(s):
Wheat LJ, Study Chair
Summary
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.
Clinical Details
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
Study design: Treatment, Efficacy Study
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
Minimum age: 13 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Univ of Alabama at Birmingham, Birmingham, Alabama 35294, United States
San Francisco Veterans Administration Med Ctr, San Francisco, California 94121, United States
Univ of Southern California / LA County USC Med Ctr, Los Angeles, California 900331079, United States
Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States
Methodist Hosp of Indiana / Life Care Clinic, Indianapolis, Indiana 46202, United States
Baystate Med Ctr of Springfield, Springfield, Massachusetts 01199, United States
Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial, Worcester, Massachusetts 01605, United States
St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis, Missouri 63112, United States
Univ of Missouri at Kansas City School of Medicine, Kansas City, Missouri 641082792, United States
Infectious Diseases Association / Research Med Ctr, Kansas City, Missouri 64132, United States
Montefiore Drug Treatment Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States
Montefiore Family Health Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States
Samaritan Village Inc / Bronx Municipal Hosp, Bronx, New York 10461, United States
Mount Sinai Med Ctr, New York, New York 10029, United States
Cornell Univ Med Ctr, New York, New York 10021, United States
Saint Luke's - Roosevelt Hosp Ctr, New York, New York 10025, United States
Montefiore Med Ctr / Bronx Municipal Hosp, Bronx, New York 10467, United States
Beth Israel Med Ctr, New York, New York 10003, United States
North Central Bronx Hosp / Bronx Municipal Hosp, Bronx, New York 10467, United States
Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States
Julio Arroyo, West Columbia, South Carolina 29169, United States
Univ TX Health Science Ctr, Houston, Texas 77030, United States
Houston Veterans Administration Med Ctr, Houston, Texas 77030, United States
Additional Information
Click here for more information about Fluconazole
Related publications: Wheat J, Vanden Bossche H, Marichal P. Mechanism for resistance of Histoplasma capsulatum to fluconazole. Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:157 Wheat J, MaWhinney S, Hafner R, McKinsey D, Chen D, Korzun A, Shakan KJ, Johnson P, Hamill R, Bamberger D, Pappas P, Stansell J, Koletar S, Squires K, Larsen RA, Cheung T, Hyslop N, Lai KK, Schneider D, Kauffman C, Saag M, Dismukes W, Powderly W. Treatment of histoplasmosis with fluconazole in patients with acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Acquired Immunodeficiency Syndrome Clinical Trials Group and Mycoses Study Group. Am J Med. 1997 Sep;103(3):223-32.
Last updated: June 23, 2005
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