To compare the efficacy and safety of clarithromycin alone versus rifabutin alone versus the two drugs in combination for the prevention or delay of Mycobacterium avium Complex (MAC) bacteremia or disseminated MAC disease. To compare other parameters such as survival, toxicity, and quality of life among the three treatment arms. To obtain information on the incidence and clinical grade of...
Date First Received: November 2, 1999
Last Updated: July 29, 2008
Verified by: National Institute of Allergy and Infectious Diseases (NIAID), January 2003
Clinical Trial Phase: Phase 3 | Start Date:
Overall Status: Completed
Estimated Enrollment: 1100
Brief Summary
Official Title: “A Prospective, Randomized, Comparative Study of the Safety and Efficacy of Clarithromycin Versus Rifabutin Versus the Combination of Clarithromycin Plus Rifabutin for the Prevention of Mycobacterium Avium Complex (MAC) Bacteremia or Disseminated MAC Disease in HIV-Infected Patients With CD4 Lymphocyte Counts <= 100 Cells/mm3”
Condition Keyword(s):
Intervention(s):
To compare the efficacy and safety of clarithromycin alone versus rifabutin alone versus the two drugs in combination for the prevention or delay of Mycobacterium avium Complex (MAC) bacteremia or disseminated MAC disease. To compare other parameters such as survival, toxicity, and quality of life among the three treatment arms. To obtain information on the incidence and clinical grade of targeted gynecologic conditions.
Persons with advanced stages of HIV are considered to be at particular risk for developing disseminated MAC disease. The development of an effective regimen for the prevention of disseminated MAC disease may be of substantial benefit in altering the morbidity and possibly the mortality associated with this disease and its treatment.
Study Type: Interventional
Study Design: Treatment
Detailed Clinical Trial Description
Persons with advanced stages of HIV are considered to be at particular risk for developing disseminated MAC disease. The development of an effective regimen for the prevention of disseminated MAC disease may be of substantial benefit in altering the morbidity and possibly the mortality associated with this disease and its treatment.
Patients are randomized to receive clarithromycin alone, rifabutin alone, or the two drugs in combination daily. Patients are evaluated every 4 weeks for the first 8 weeks and every 8 weeks thereafter for the duration of the study. Patients are followed for 24 months. Per amendment, a pharmacokinetic substudy will be conducted.
Intervention(s) in this Clinical Trial
- Drug: Clarithromycin
- Drug: Rifabutin
Criteria for Participation in this Clinical Trial
Inclusion Criteria
Concurrent Medication:
Recommended:
- PCP prophylaxis.
Allowed:
- GM-CSF or G-CSF.
- Erythropoietin.
- Therapies (including antiretrovirals) available through expanded access or treatment
- IND programs.
- Other non-experimental therapies available by prescription.
- Antihistamines other than those specifically excluded.
Patients must have:
- Evidence or diagnosis of HIV infection or a history of an AIDS-defining condition by CDC criteria.
- CD4 count <= 100 cells/mm3 within 90 days prior to study entry.
- Two baseline blood sample cultures negative for MAC within 30 days of study entry.
- No suspected disseminated MAC disease, in the opinion of the clinician.
NOTE:
- Patients with elevated GGT and/or triglycerides are allowed.
NOTE:
- Patients may co-enroll on ACTG 081/981/181, ACTG 175, ACTG 204, ACTG 193, ACTG 241, or other acceptable protocols.
Exclusion Criteria
Co-existing Condition:
Patients with the following symptoms or conditions are excluded:
- Known or suspected tuberculous infection or other non-tuberculous mycobacterial infection requiring chemotherapy or chemoprophylaxis (with the exception of isoniazid prophylaxis alone).
NOTE:
- Patients may enroll who successfully completed tuberculosis (TB) treatment and have been off anti-TB drugs for more than 6 months with no symptoms of mycobacterial infection.
- Active TB.
- Known hypersensitivity to study drugs.
- Malabsorption as defined by persistent diarrhea with more than 8 stools per day for >
- 6 weeks.
Concurrent Medication:
Excluded:
- Frequent (more than once per month), repeated, or continuous treatment courses of quinolones, erythromycin, spiramycin, azithromycin, clarithromycin, or clindamycin.
- Concomitant terfenadine or astemizole.
Prior Medication:
Excluded:
- Prophylaxis with azithromycin, clarithromycin, or rifabutin for more than 4 months.
Gender Eligibility for this Clinical Trial: Both
Minimum Age for this Clinical Trial: 12 Years
Maximum Age for this Clinical Trial: N/A
Are Healthy Volunteers Accepted for this Clinical Trial?: No
Clinical Trial Sponsor Information
Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Overall Clinical Trial Officials and Contacts
Benson CA Study Chair
Related Publications
References
Currier JS, Williams P, Feinberg J, Becker S, Owens S, Benson CA. ACTG 815: a prospective study of bacterial infections in advanced HIV disease. Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:131 (abstract no 364)
Mascolini M. FDA advisory committee deadlocks on delavirdine. Food and Drug Administration. AIDS Treat News. 1996 Dec 6;(No 260):3-5. No abstract available.
Watts DH, Spino C, Benson C, Yu B, Katzenstein D, Hammer S, Stratton P, Korvick J. A comparison of gynecologic findings in HIV-positive women with CD4 lymphocyte counts 200 to 500/cc and less than 100/cc. Int Conf AIDS. 1996 Jul 7-12;11(2):275 (abstract no ThB4137)
Fichtenbaum CJ, Zackin R, Feinberg J, Benson C, Griffiths JK. Rifabutin but not clarithromycin prevents cryptosporidiosis in persons with advanced HIV infection. AIDS. 2000 Dec 22;14(18):2889-93.
Cohn DL. Prevention strategies for Mycobacterium avium-intracellulare complex (MAC) infection. A review of recent studies in patients with AIDS. Drugs. 1997;54 Suppl 2:8-15; discussion 28-9. Review.
Watts DH, Spino C, Zaborski L, Katzenstein D, Hammer S, Benson C. Comparison of gynecologic history and laboratory results in HIV-positive women with CD4+ lymphocyte counts between 200 and 500 cells/microl and below 100 cells/microl. J Acquir Immune Defic Syndr Hum Retrovirol. 1999 Apr 15;20(5):455-62.
Fichtenbaum CJ, Powderly WG. Refractory mucosal candidiasis in patients with human immunodeficiency virus infection. Clin Infect Dis. 1998 Mar;26(3):556-65. Review.
Benson CA, Williams PL, Cohn DL, Becker S, Hojczyk P, Nevin T, Korvick JA, Heifets L, Child CC, Lederman MM, Reichman RC, Powderly WG, Notario GF, Wynne BA, Hafner R. Clarithromycin or rifabutin alone or in combination for primary prophylaxis of Mycobacterium avium complex disease in patients with AIDS: A randomized, double-blind, placebo-controlled trial. The AIDS Clinical Trials Group 196/Terry Beirn Community Programs for Clinical Research on AIDS 009 Protocol Team. J Infect Dis. 2000 Apr;181(4):1289-97.
Currier JS, Williams P, Feinberg J, Becker S, Owens S, Fichtenbaum C, Benson C. Impact of prophylaxis for Mycobacterium avium complex on bacterial infections in patients with advanced human immunodeficiency virus disease. Clin Infect Dis. 2001 Jun 1;32(11):1615-22.
Additional Information
Information obtained from ClinicalTrials.gov on January 06, 2009
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00001030
Study ID Number: ACTG 196
ClinicalTrials.gov Identifier: NCT00001030
Health Authority: United States: Federal Government
Clinical Trials Authorship and Review
Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.
