The Safety and Effectiveness of Clarithromycin and Rifabutin Used Alone or in Combination to Prevent Mycobacterium Avium Complex (MAC) or Disseminated MAC Disease in HIV-Infected Patients

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00001030
• Collaborator: (none)
• Enrollment: 1,100
• Locations: 42
• Patients Per Site: 26.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Mycobacterium Avium-intracellulare Infection; HIV Infections	Drug: Clarithromycin; Drug: Rifabutin	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional
• Primary Purpose: Treatment
• 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
• Actual Study Completion Date: Jun 1, 1996

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Therapeutics CRS	Birmingham	Alabama	United States	35294
2	UCLA CARE Center CRS	Los Angeles	California	United States	90095
3	Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.	Oakland	California	United States	94609
4	Ucsf Aids Crs	San Francisco	California	United States
5	Howard University Hosp., Div. of Infectious Diseases, ACTU	Washington	District of Columbia	United States	20059
6	Univ. of Miami AIDS CRS	Miami	Florida	United States	33136
7	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii	United States	96816
8	Chicago Children's CRS	Chicago	Illinois	United States	60611
9	Northwestern University CRS	Chicago	Illinois	United States	60611
10	Cook County Hosp. CORE Ctr.	Chicago	Illinois	United States	60612
11	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois	United States	60612
12	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana	United States	46202
13	Methodist Hosp. of Indiana	Indianapolis	Indiana	United States	46202
14	Univ. of Iowa Healthcare, Div. of Infectious Diseases	Iowa City	Iowa	United States	52242
15	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States	21287
16	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts	United States	02114
17	Bmc Actg Crs	Boston	Massachusetts	United States	02118
18	Beth Israel Deaconess - East Campus A0102 CRS	Boston	Massachusetts	United States	02215
19	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts	United States	02215
20	Hennepin County Med. Ctr., Div. of Infectious Diseases	Minneapolis	Minnesota	United States	55415
21	University of Minnesota, ACTU	Minneapolis	Minnesota	United States	55455
22	St. Louis ConnectCare, Infectious Diseases Clinic	Saint Louis	Missouri	United States
23	Washington U CRS	Saint Louis	Missouri	United States
24	Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.	Omaha	Nebraska	United States	68198
25	Bronx-Lebanon Hosp. IMPAACT CRS	Bronx	New York	United States	10457
26	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York	United States	14215
27	NY Univ. HIV/AIDS CRS	New York	New York	United States	10016
28	Memorial Sloan-Kettering Cancer Ctr.	New York	New York	United States	10021
29	Beth Israel Med. Ctr. (Mt. Sinai)	New York	New York	United States	10029
30	Cornell University A2201	New York	New York	United States
31	Univ. of Rochester ACTG CRS	Rochester	New York	United States	14642
32	Unc Aids Crs	Chapel Hill	North Carolina	United States	27599
33	Carolinas HealthCare System, Carolinas Med. Ctr.	Charlotte	North Carolina	United States	28203
34	Regional Center for Infectious Disease, Wendover Medical Center CRS	Greensboro	North Carolina	United States	27401
35	Univ. of Cincinnati CRS	Cincinnati	Ohio	United States	45267
36	Case CRS	Cleveland	Ohio	United States	44106
37	MetroHealth CRS	Cleveland	Ohio	United States	44109
38	The Ohio State Univ. AIDS CRS	Columbus	Ohio	United States	43210
39	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania	United States	19104
40	The Children's Hosp. of Philadelphia IMPAACT CRS	Philadelphia	Pennsylvania	United States	19104
41	University of Washington AIDS CRS	Seattle	Washington	United States	98122
42	Mbeya Med. Research Program, Mbeya Referral Hosp. CRS	Mbeya		Tanzania

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Chair: Benson CA,
• Study Chair: Cohn DL,

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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. Epub 2000 Apr 13.
• 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.
• 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)
• Currier JS, Williams P, Feinberg J, Becker S, Owens S, Fichtenbaum C, Benson C; Adult Clinical Trial Group. 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. Epub 2001 Apr 30.
• Fichtenbaum CJ, Powderly WG. Refractory mucosal candidiasis in patients with human immunodeficiency virus infection. Clin Infect Dis. 1998 Mar;26(3):556-65. Review.
• Fichtenbaum CJ, Zackin R, Feinberg J, Benson C, Griffiths JK; AIDS Clinical Trials Group New Works Concept Sheet Team 064. Rifabutin but not clarithromycin prevents cryptosporidiosis in persons with advanced HIV infection. AIDS. 2000 Dec 22;14(18):2889-93.
• Mascolini M. FDA advisory committee deadlocks on delavirdine. Food and Drug Administration. AIDS Treat News. 1996 Dec 6;(No 260):3-5.
• 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)
• 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.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00001030
• Other Study ID Numbers: ACTG 196; CPCRA 009; 11172
• First Posted: Aug 31, 2001
• Last Update Posted: Nov 1, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Rifabutin; Mycobacterium avium-intracellulare Infection; Acquired Immunodeficiency Syndrome; Clarithromycin
• Additional relevant MeSH terms: Infections; Communicable Diseases; Mycobacterium Infections; Mycobacterium avium-intracellulare Infection; Clarithromycin; Rifabutin

Study Results

No Results Posted as of Nov 1, 2021