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

Tracking Information
First Submitted Date ICMJE	November 2, 1999
First Posted Date ICMJE	August 31, 2001
Last Update Posted Date	April 2, 2012
Study Start Date ICMJE	Not Provided
Primary Completion Date	Not Provided
Current Primary Outcome Measures ICMJE	Not Provided
Original Primary Outcome Measures ICMJE	Not Provided
Change History	Complete list of historical versions of study NCT00000627 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	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 ICMJE	Pilot Study to Determine the Feasibility of Fluconazole for Induction Treatment and Suppression of Relapse of Histoplasmosis in Patients With the Acquired Immunodeficiency Syndrome
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.
Study Type ICMJE	Interventional
Study Phase	Not Applicable
Study Design ICMJE	Primary Purpose: Treatment
Condition ICMJE	HIV Infections; Histoplasmosis
Intervention ICMJE	Drug: Fluconazole
Study Arms	Not Provided
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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Enrollment ICMJE; (submitted: June 23, 2005)	90
Original Enrollment ICMJE	Same as current
Actual Study Completion Date	November 1994
Primary Completion Date	Not Provided
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: All
Ages	13 Years and older (Child, Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00000627
Other Study ID Numbers ICMJE	ACTG 174; R-0245; 11149 ( Registry Identifier: DAIDS ES Registry Number )
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor ICMJE	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators ICMJE	Pfizer
Investigators ICMJE	Study Chair: Wheat LJ
PRS Account	National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date	March 2012
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP