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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000627

Collaborator

Pfizer (Industry)

Enrollment

Locations

3.9

Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections Histoplasmosis	Drug: Fluconazole	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

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

Actual Study Completion Date :

Nov 1, 1994

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Univ of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Univ of Southern California / LA County USC Med Ctr	Los Angeles	California	United States	900331079
3	San Francisco Veterans Administration Med Ctr	San Francisco	California	United States	94121
4	Indiana Univ Hosp	Indianapolis	Indiana	United States	462025250
5	Methodist Hosp of Indiana / Life Care Clinic	Indianapolis	Indiana	United States	46202
6	Baystate Med Ctr of Springfield	Springfield	Massachusetts	United States	01199
7	Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial	Worcester	Massachusetts	United States	01605
8	Univ of Missouri at Kansas City School of Medicine	Kansas City	Missouri	United States	641082792
9	Infectious Diseases Association / Research Med Ctr	Kansas City	Missouri	United States	64132
10	St Louis Regional Hosp / St Louis Regional Med Ctr	Saint Louis	Missouri	United States	63112
11	Montefiore Drug Treatment Ctr / Bronx Municipal Hosp	Bronx	New York	United States	10461
12	Montefiore Family Health Ctr / Bronx Municipal Hosp	Bronx	New York	United States	10461
13	Samaritan Village Inc / Bronx Municipal Hosp	Bronx	New York	United States	10461
14	Montefiore Med Ctr / Bronx Municipal Hosp	Bronx	New York	United States	10467
15	North Central Bronx Hosp / Bronx Municipal Hosp	Bronx	New York	United States	10467
16	Beth Israel Med Ctr	New York	New York	United States	10003
17	Cornell Univ Med Ctr	New York	New York	United States	10021
18	Saint Luke's - Roosevelt Hosp Ctr	New York	New York	United States	10025
19	Mount Sinai Med Ctr	New York	New York	United States	10029
20	Ohio State Univ Hosp Clinic	Columbus	Ohio	United States	432101228
21	Julio Arroyo	West Columbia	South Carolina	United States	29169
22	Houston Veterans Administration Med Ctr	Houston	Texas	United States	77030
23	Univ TX Health Science Ctr	Houston	Texas	United States	77030