A Comparison of Three Drug Combinations Containing Clarithromycin in the Treatment of Mycobacterium Avium Complex (MAC) Disease in Patients With AIDS

NCT00001058 | Completed Phase 2

• 2 other identifiers: ACTG 22311200
• Study Type: interventional
• Target: 246
• Locations: 2 countries
• Sites: 34

Brief Summary

To compare the efficacy and safety of clarithromycin combined with rifabutin, ethambutol, or both in the treatment of disseminated Mycobacterium avium Complex (MAC) disease in persons with AIDS, including individuals who have or have not received prior MAC prophylaxis. It is believed that effective therapy for MAC disease in patients with AIDS requires combinations of two or more antimycobacterial agents in order to overcome drug resistance and the unfavorable influence of the profound immunosuppression associated with AIDS. Data suggest that clarithromycin may have substantial activity in two- or three-drug combination regimens with clofazimine, rifamycin derivatives, ethambutol, or the 4-quinolones.

Conditions

Mycobacterium Avium-intracellulare Infection; HIV Infections

Keywords

Rifabutin; Mycobacterium avium-intracellulare Infection; Drug Therapy, Combination; Ethambutol; Clofazimine; Acquired Immunodeficiency Syndrome; Ciprofloxacin; Clarithromycin

Interventions

Indinavir sulfate DRUG

Ritonavir DRUG

Ethambutol hydrochloride DRUG

Clarithromycin DRUG

Rifabutin DRUG

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Concurrent Medication:
• Allowed:
• Antiretroviral therapy.
• Maintenance or prophylactic therapy for other opportunistic infections (with the exception of specifically excluded drugs).
• Carbamazepine or theophylline.
• Isoniazid for TB prophylaxis.
• PER AMENDMENT 10/10/96:
• Therapy for acute infectious processes, other than MAC, provided that the patient is stable on the therapy.
• Fluconazole therapy for maintenance or suppression of fungal infections, providing the patient has been on a stable dose for at least 4 weeks.
• PER AMENDMENT 7/02/97:
• If a patient elects to receive indinavir, ORTHO/NOVUM 1/35 is an acceptable means of birth control.
• Patients must have:
• HIV infection.
• Disseminated MAC disease.
• Life expectancy of at least 8 weeks.

You may not qualify if:

• Co-existing Condition:
• Patients with the following symptoms or conditions are excluded:
• Active mycobacterial infection other than MAC that requires treatment, with the exception of isoniazid used solely for TB prophylaxis.
• Concurrent Medication:
• Excluded:
• Other antimycobacterial drugs (with the exception of isoniazid for TB prophylaxis).
• Other investigational drugs unless approved by protocol chair.
• PER AMENDMENT 7/2/97:
• For patients who elect to receive indinavir or ritonavir:
• Terfenadine, astemizole, cisapride, triazolam, or midazolam.
• For patients who elect to receive ritonavir:
• alprazolam, amiodarone, bepridil, bupropion, cisapride, clorazepate, clozapine, diazepam, dihydroergotamine, ergotamine, estazolam, encainide, flecainide, flurazepam, meperidine, pimozide, piroxicam, propafenone, propoxyphene, quinidine or zolpidem.
• For patients who elect to receive indinavir:
• oral contraceptives other than ORTHO/NOVUM as a sole form of birth control.
• For patients randomized to a rifabutin-containing arm:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (34)

Alabama Therapeutics CRS

Birmingham, Alabama, 35294, United States

Location

USC CRS

Los Angeles, California, 90033, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

Ucsd, Avrc Crs

San Diego, California, 92103, United States

Location

Ucsf Aids Crs

San Francisco, California, 94110, United States

Location

Harbor-UCLA Med. Ctr. CRS

Torrance, California, 90502, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

The Ponce de Leon Ctr. CRS

Atlanta, Georgia, 30308, United States

Location

Queens Med. Ctr.

Honolulu, Hawaii, 96813, United States

Location

Univ. of Hawaii at Manoa, Leahi Hosp.

Honolulu, Hawaii, 96816, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Cook County Hosp. CORE Ctr.

Chicago, Illinois, 60612, United States

Location

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, 60612, United States

Location

Weiss Memorial Hosp.

Chicago, Illinois, 60640, United States

Location

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, 46202, United States

Location

Indiana Univ. School of Medicine, Wishard Memorial

Indianapolis, Indiana, 46202, United States

Location

Methodist Hosp. of Indiana

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, 21287, United States

Location

Bmc Actg Crs

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess - East Campus A0102 CRS

Boston, Massachusetts, 02215, United States

Location

Hennepin County Med. Ctr., Div. of Infectious Diseases

Minneapolis, Minnesota, 55415, United States

Location

University of Minnesota, ACTU

Minneapolis, Minnesota, 55455, United States

Location

Washington U CRS

St Louis, Missouri, 63110, United States

Location

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, 63112, United States

Location

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, 14260, United States

Location

Beth Israel Med. Ctr. (Mt. Sinai)

New York, New York, 10003, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, 10016, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642, United States

Location

Unc Aids Crs

Chapel Hill, North Carolina, 27514, United States

Location

Univ. of Cincinnati CRS

Cincinnati, Ohio, 45267, United States

Location

The Ohio State Univ. AIDS CRS

Columbus, Ohio, 43210, United States

Location

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, 19104, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104, United States

Location

Mbeya Med. Research Program, Mbeya Referral Hosp. CRS

Mbeya, Tanzania

Location

Related Publications (2)

• Flexner C, Noe D, Benson C, Currier J, Andrade A, Shaver A. Adherence patterns in patients with symptomatic Mycobacterium avium complex (MAC) infection taking a twice-daily clarithromycin regimen. ACTG 223 Study Team. Int Conf AIDS. 1998;12:585 (abstract no 32324)

  BACKGROUND

• Benson CA, Williams PL, Currier JS, Holland F, Mahon LF, MacGregor RR, Inderlied CB, Flexner C, Neidig J, Chaisson R, Notario GF, Hafner R; AIDS Clinical Trials Group 223 Protocol Team. A prospective, randomized trial examining the efficacy and safety of clarithromycin in combination with ethambutol, rifabutin, or both for the treatment of disseminated Mycobacterium avium complex disease in persons with acquired immunodeficiency syndrome. Clin Infect Dis. 2003 Nov 1;37(9):1234-43. doi: 10.1086/378807. Epub 2003 Oct 3.

  PMID: 14557969 BACKGROUND

MeSH Terms

Conditions

Mycobacterium avium-intracellulare Infection; HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Indinavir; Ritonavir; Ethambutol; Clarithromycin; Rifabutin

Condition Hierarchy (Ancestors)

Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Ethylenediamines; Diamines; Polyamines; Amines; Erythromycin; Macrolides; Polyketides; Lactones; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Benson CA

  STUDY CHAIR

• Chaisson RE

  STUDY CHAIR

• Currier JS

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: January 1, 1999
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

US (33); TA (1)