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)

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000676
First received: November 2, 1999
Last updated: March 28, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Candidiasis
Mycoses
HIV Infections
Drug: Clotrimazole
Drug: Fluconazole
Phase 3

Study Type: Interventional
Study Design: Primary Purpose: Prevention
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 500
Study Completion Date: November 1993
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000676

  Hide Study Locations
Locations
United States, California
Stanford CRS
Palo Alto, California, United States
Ucsd, Avrc Crs
San Diego, California, United States, 92093
Ucsf Aids Crs
San Francisco, California, United States
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 33136
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana, United States
United States, Maryland
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Beth Israel Deaconess - East Campus A0102 CRS
Boston, Massachusetts, United States, 02215
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States, 02215
Bmc Actg Crs
Boston, Massachusetts, United States, 02118
United States, Minnesota
University of Minnesota, ACTU
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington U CRS
St. Louis, Missouri, United States
United States, New York
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States, 14215
Memorial Sloan-Kettering Cancer Ctr.
New York, New York, United States, 10021
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, United States, 27710
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States
Case CRS
Cleveland, Ohio, United States, 44106
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Pitt CRS
Pittsburgh, Pennsylvania, United States, 15213
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98122
Tanzania
Mbeya Med. Research Program, Mbeya Referral Hosp. CRS
Mbeya, Tanzania
Sponsors and Collaborators
Pfizer
Investigators
Study Chair: Bozzettee S
Study Chair: Powderly WG
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000676     History of Changes
Other Study ID Numbers: ACTG 981, 11504
Study First Received: November 2, 1999
Last Updated: March 28, 2012
Health Authority: Unspecified

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Mycoses
Fluconazole
Clotrimazole
Antifungal Agents
Acquired Immunodeficiency Syndrome
AIDS-Related Complex

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
AIDS-Related Complex
Candidiasis
Mycoses
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Clotrimazole
Miconazole
Fluconazole
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents

ClinicalTrials.gov processed this record on July 08, 2014