A Comparison of Three Drug Combinations Containing Clarithromycin in the Treatment of Mycobacterium Avium Complex (MAC) Disease in Patients With AIDS
NCT ID: NCT00001058
Last Updated: 2021-11-01
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
246 participants
INTERVENTIONAL
1999-01-31
Brief Summary
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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.
Detailed Description
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Patients are randomized to one of three treatment arms containing clarithromycin in combination with ethambutol, rifabutin, or both. Clarithromycin alone is taken on days 1 through 3 to determine tolerance and rifabutin and/or ethambutol is added on day 3. AS PER AMENDMENT 7/2/97: Patients may elect to add ritonavir or indinavir to their treatment regimen. Treatment continues daily for 48 weeks. In the absence of a dose-limiting toxicity, those patients who are determined to be complete or partial responders continue on the regimen to which they were originally assigned. Patients who have failed or relapsed on originally assigned MAC therapy, must have their therapy amended to receive clarithromycin and at least two other drugs not included in their originally assigned regimen. Patients are followed twice in the first week, then every 2 weeks for the first 2 months, then monthly for the next 4 months, and then every 2 months thereafter until the end of 12 months. PER AMENDMENT 10/10/96: NOTE: Any patient who develops a toxicity to rifabutin or ethambutol after week 12 or thereafter will be offered the option of being registered to a salvage regimen of 2 new drugs not previously received, plus clarithromycin to continue for the study duration.
Conditions
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Keywords
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Study Design
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TREATMENT
Interventions
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Indinavir sulfate
Ritonavir
Ethambutol hydrochloride
Clarithromycin
Rifabutin
Eligibility Criteria
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Inclusion Criteria
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.
* Consent of parent or guardian if under 18 years of age.
NOTE:
* This protocol is approved for prisoner participation.
Prior Medication:
Allowed:
PER AMENDMENT 10/10/96:
* Therapy for acute infectious processes, other than MAC, prior to study entry.
Exclusion Criteria
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:
* oral contraceptives or Norplant as a sole form of birth control.
Patients with the following prior condition are excluded:
* History of severe hypersensitivity to erythromycin, clarithromycin, azithromycin, ethambutol, rifampin, or rifabutin (including Type 1 hypersensitivity reaction, Stevens-Johnson syndrome, hepatitis, optic neuritis, or exfoliative dermatitis).
Prior Medication:
Excluded:
* Empiric or presumptive antimycobacterial therapy prior to study entry if \> 14 days, within 90 days prior to entry.
NOTE:
* Patients unwilling to discontinue presumptive therapy or empiric therapy may be enrolled with the permission of the protocol chairs, however, if they are without a MAC positive blood culture at baseline, they will have study medications discontinued (AS PER AMENDMENT 7/2/97).
PER AMENDMENT 10/10/96:
* Treatment with clarithromycin or ethambutol within 4 days of initiation of study medications.
* Treatment with rifabutin or rifampin within 7 days of initiation of study medications.
13 Years
ALL
No
Sponsors
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National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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Benson CA
Role: STUDY_CHAIR
Chaisson RE
Role: STUDY_CHAIR
Currier JS
Role: STUDY_CHAIR
Locations
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Alabama Therapeutics CRS
Birmingham, Alabama, United States
USC CRS
Los Angeles, California, United States
UCLA CARE Center CRS
Los Angeles, California, United States
Ucsd, Avrc Crs
San Diego, California, United States
Ucsf Aids Crs
San Francisco, California, United States
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States
University of Colorado Hospital CRS
Aurora, Colorado, United States
The Ponce de Leon Ctr. CRS
Atlanta, Georgia, United States
Queens Med. Ctr.
Honolulu, Hawaii, United States
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States
Northwestern University CRS
Chicago, Illinois, United States
Cook County Hosp. CORE Ctr.
Chicago, Illinois, United States
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States
Weiss Memorial Hosp.
Chicago, Illinois, United States
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States
Indiana Univ. School of Medicine, Wishard Memorial
Indianapolis, Indiana, United States
Methodist Hosp. of Indiana
Indianapolis, Indiana, United States
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States
Bmc Actg Crs
Boston, Massachusetts, United States
Beth Israel Deaconess - East Campus A0102 CRS
Boston, Massachusetts, United States
Hennepin County Med. Ctr., Div. of Infectious Diseases
Minneapolis, Minnesota, United States
University of Minnesota, ACTU
Minneapolis, Minnesota, United States
Washington U CRS
St Louis, Missouri, United States
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, United States
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, United States
NY Univ. HIV/AIDS CRS
New York, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States
Unc Aids Crs
Chapel Hill, North Carolina, United States
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States
University of Washington AIDS CRS
Seattle, Washington, United States
Mbeya Med. Research Program, Mbeya Referral Hosp. CRS
Mbeya, , Tanzania
Countries
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References
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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)
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.
Other Identifiers
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11200
Identifier Type: REGISTRY
Identifier Source: secondary_id
ACTG 223
Identifier Type: -
Identifier Source: org_study_id