- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00000676
Randomized Comparative Study of Fluconazole Versus Clotrimazole Troches in the Prevention of Serious Fungal Infection in Patients With AIDS or Advanced AIDS-Related Complex. (A Nested Study of ACTG 081)
To study the effectiveness, safety, and tolerance of fluconazole versus clotrimazole troches (lozenges) as prophylaxis (preventive treatment) against fungal infections in patients enrolled in ACTG 081 (a study of prophylaxis against pneumocystosis, toxoplasmosis, and serious bacterial infection). Primarily, to compare the rates of invasive infections by C. neoformans, endemic mycoses, and Candida. To compare the mortality rates due to fungal infections between two antifungal prophylactic treatments. Secondarily, to assess the effect of prophylaxis on the incidence of severe fungal infections, defined as invasive infections and esophageal candidiasis and less severe mucocutaneous infection.
Serious fungal infections are significant complicating and life-threatening occurrences in patients with advanced HIV infection. Oropharyngeal candidiasis is found in almost all such patients, and causes pain, difficulty in swallowing, and loss of appetite. Similarly, esophageal candidiasis causes illness in the population. Cryptococcosis, endemic mycoses, and coccidioidomycosis also cause significant illness and death in AIDS patients. Once established, fungal infections in AIDS patients generally require continuous suppressive therapy because attempts at curing these infections are usually unsuccessful. Fluconazole has a number of characteristics that would make it a logical candidate to examine as a prophylactic agent in patients with advanced HIV infection. Animal studies have shown it to be prophylactic in models of candidiasis, cryptococcosis, histoplasmosis, and coccidioidomycosis. Initial experience in patients with active cryptococcal meningitis appears favorable, and studies of oropharyngeal candidiasis show it to be effective.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Serious fungal infections are significant complicating and life-threatening occurrences in patients with advanced HIV infection. Oropharyngeal candidiasis is found in almost all such patients, and causes pain, difficulty in swallowing, and loss of appetite. Similarly, esophageal candidiasis causes illness in the population. Cryptococcosis, endemic mycoses, and coccidioidomycosis also cause significant illness and death in AIDS patients. Once established, fungal infections in AIDS patients generally require continuous suppressive therapy because attempts at curing these infections are usually unsuccessful. Fluconazole has a number of characteristics that would make it a logical candidate to examine as a prophylactic agent in patients with advanced HIV infection. Animal studies have shown it to be prophylactic in models of candidiasis, cryptococcosis, histoplasmosis, and coccidioidomycosis. Initial experience in patients with active cryptococcal meningitis appears favorable, and studies of oropharyngeal candidiasis show it to be effective.
AMENDED: 11/01/90 Sufficient numbers of patients will be enrolled from all centers starting at week 8 of participation in the parent study to achieve a total of 240 evaluable patients who will remain in the nested study for a maximum duration of 45 months. Enrollment will continue until all eligible and interested 081 patients are enrolled. Fungal prophylaxis will begin at the time of enrollment into the nested study and will continue until an efficacy or safety end point is reached, until withdrawal from the nested study, or until death.
Original design: Patients included are those already enrolled in ACTG 081. Patients are enrolled from all centers at either week 8, 12, 16, 20, 24, 28, or 32 of participation in the parent study. They are randomized to receive either oral fluconazole or clotrimazole troches. Prophylaxis continues until a serious fungal infection develops, the end of the parent study is reached (which is expected to be December 1991), the patient withdraws from either the nested or parent study, or the patient dies. Clinical examination is performed at 2 weeks and then monthly (or more if clinically indicated) for the duration of antifungal prophylaxis; the schedule of evaluation is the same as for the parent study. There is a 1-month postprophylaxis follow-up after discontinuation of prophylaxis for any reason.
Study Type
Enrollment
Phase
- Phase 3
Contacts and Locations
Study Locations
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Mbeya, Tanzania
- Mbeya Med. Research Program, Mbeya Referral Hosp. CRS
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California
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Palo Alto, California, United States
- Stanford CRS
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San Diego, California, United States, 92093
- Ucsd, Avrc Crs
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San Francisco, California, United States
- Ucsf Aids Crs
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Florida
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Miami, Florida, United States, 33136
- Univ. of Miami AIDS CRS
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Illinois
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Chicago, Illinois, United States
- Northwestern University CRS
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Chicago, Illinois, United States
- Rush Univ. Med. Ctr. ACTG CRS
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Indiana
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Indianapolis, Indiana, United States, 46202
- Indiana Univ. School of Medicine, Infectious Disease Research Clinic
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Louisiana
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New Orleans, Louisiana, United States
- Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins Adult AIDS CRS
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Massachusetts
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Boston, Massachusetts, United States, 02118
- Bmc Actg Crs
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Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Med. Ctr., ACTG CRS
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Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess - East Campus A0102 CRS
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- University of Minnesota, ACTU
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Missouri
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Saint Louis, Missouri, United States
- Washington U CRS
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New York
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Buffalo, New York, United States, 14215
- SUNY - Buffalo, Erie County Medical Ctr.
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New York, New York, United States, 10021
- Memorial Sloan-Kettering Cancer Ctr.
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New York, New York, United States
- Beth Israel Med. Ctr. (Mt. Sinai)
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Rochester, New York, United States
- Univ. of Rochester ACTG CRS
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North Carolina
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Chapel Hill, North Carolina, United States
- Unc Aids Crs
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Durham, North Carolina, United States, 27710
- Duke Univ. Med. Ctr. Adult CRS
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Ohio
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Cincinnati, Ohio, United States
- Univ. of Cincinnati CRS
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Cleveland, Ohio, United States, 44106
- Case CRS
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Columbus, Ohio, United States, 43210
- The Ohio State Univ. AIDS CRS
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213
- Pitt CRS
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Washington
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Seattle, Washington, United States, 98122
- University of Washington AIDS CRS
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria
Concurrent Medication:
Required:
- Zidovudine (AZT).
- Antipneumocystis prophylaxis.
Allowed:
- Topical suppressive antifungal agents.
Eligibility requirements are:
- Participation in NIAID ACTG 081.
- No history of systemic fungal infection, including esophageal or systemic candidiasis, cryptococcosis, histoplasmosis, coccidioidomycosis, blastomycosis, sporotrichosis, or aspergillosis.
- Willingness to sign an informed consent.
- Transaminases < 5 x upper limit of normal.
- Noncompliance will not be a reason for withdrawal of a patient from the study, unless patient refuses further treatment.
Allowed:
- A history of oropharyngeal, vaginal or cutaneous candidiasis.
- Dermatophyte infections (i.e., tinea pedis) at entry but not active candida infection. Sites of suspected dermatophyte involvement other than the feet should have candida excluded by culture.
Prior Medication:
Allowed:
- Topical suppressive antifungal agents.
Exclusion Criteria
Co-existing Condition:
Patients with the following conditions or diseases are excluded:
- History of systemic fungal infection, including esophageal or systemic candidiasis, cryptococcosis, histoplasmosis, coccidioidomycosis, blastomycosis, sporotrichosis, or aspergillosis.
- Active systemic fungal infection at time of enrollment.
- Active superficial fungal infection at time of entry. (Such patients may be treated with topical antifungal agents and may be randomized if they are in clinical remission 14 days after completion of such therapy.)
Concurrent Medication:
Excluded:
- Amphotericin B.
- Fluconazole.
- Itraconazole.
- SCH 39304.
- Other systemic antifungals.
Patients with the following are excluded:
- Previous or currently active systemic fungal infection.
- History of allergy or intolerance to imidazole or azoles.
- Positive serum cryptococcal antigen titer at any dilution.
- Requiring multi-agent therapy for tuberculosis or for symptomatic Mycobacterium avium infection.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Bozzettee S
- Study Chair: Powderly WG
Publications and helpful links
General Publications
- Glick ME. CTG studies yield results. AIDS Clinical Trials Group. NIAID AIDS Agenda. 1995 Spring:8-9.
- Hanna L. Treatment for HIV-related fungal infections. BETA. 1995 Jun:10-7.
- Powderly WG. Fungal infections. Program Abstr Intersci Conf Antimicrob Agents Chemother. 1994 Oct 4-7:274
- Powderly WG. Prophylaxis of fungal infection in HIV infection. Program Abstr Intersci Conf Antimicrob Agents Chemother. 1994 Oct 4-7:270
- Powderly WG, Finkelstein D, Feinberg J, Frame P, He W, van der Horst C, Koletar SL, Eyster ME, Carey J, Waskin H, et al. A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group. N Engl J Med. 1995 Mar 16;332(11):700-5. doi: 10.1056/NEJM199503163321102.
Study record dates
Study Major Dates
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- RNA Virus Infections
- Virus Diseases
- Blood-Borne Infections
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Disease Attributes
- Bacterial Infections and Mycoses
- Slow Virus Diseases
- HIV Infections
- Infections
- Communicable Diseases
- Candidiasis
- Mycoses
- AIDS-Related Complex
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents, Local
- Anti-Infective Agents
- Enzyme Inhibitors
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Hormone Antagonists
- Antifungal Agents
- Steroid Synthesis Inhibitors
- 14-alpha Demethylase Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors
- Clotrimazole
- Miconazole
- Fluconazole
Other Study ID Numbers
- ACTG 981
- 11504 (REGISTRY: DAIDS ES Registry Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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