Clinical trial NCT00000627: Pilot Study to Determine the Feasibility of Fluconazole for Induction Treatment and Suppression of Relapse of Histoplasmosis in Patients With the Acquired Immunodeficiency Syndrome
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Histoplasmosis
Keywords: Pilot Projects
Histoplasmosis
Drug Evaluation
Fluconazole
Acquired Immunodeficiency Syndrome
Recurrence
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Pfizer
First posted: 2001-08-31
Enrollment: 90
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Univ of Southern California / LA County USC Med Ctr
state: California
city: San Francisco
country: United States
facility: San Francisco Veterans Administration Med Ctr
state: California
city: Indianapolis
country: United States
facility: Indiana Univ Hosp
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hosp of Indiana / Life Care Clinic
state: Indiana
city: Springfield
country: United States
facility: Baystate Med Ctr of Springfield
state: Massachusetts
city: Worcester
country: United States
facility: Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial
state: Massachusetts
city: Kansas City
country: United States
facility: Univ of Missouri at Kansas City School of Medicine
state: Missouri
city: Kansas City
country: United States
facility: Infectious Diseases Association / Research Med Ctr
state: Missouri
city: Saint Louis
country: United States
facility: St Louis Regional Hosp / St Louis Regional Med Ctr
state: Missouri
city: Bronx
country: United States
facility: Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Montefiore Family Health Ctr / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Samaritan Village Inc / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: Montefiore Med Ctr / Bronx Municipal Hosp
state: New York
city: Bronx
country: United States
facility: North Central Bronx Hosp / Bronx Municipal Hosp
state: New York
city: New York
country: United States
facility: Beth Israel Med Ctr
state: New York
city: New York
country: United States
facility: Cornell Univ Med Ctr
state: New York
city: New York
country: United States
facility: Saint Luke's - Roosevelt Hosp Ctr
state: New York
city: New York
country: United States
facility: Mount Sinai Med Ctr
state: New York
city: Columbus
country: United States
facility: Ohio State Univ Hosp Clinic
state: Ohio
city: West Columbia
country: United States
facility: Julio Arroyo
state: South Carolina
city: Houston
country: United States
facility: Houston Veterans Administration Med Ctr
state: Texas
city: Houston
country: United States
facility: Univ TX Health Science Ctr
state: Texas
Study officials:
name: Wheat LJ
role: STUDY_CHAIR
References:
citation: 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
citation: 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. doi: 10.1016/s0002-9343(97)00151-4.