A prospective randomized trial of four three-drug regimens in the treatment of disseminated Mycobacterium avium complex disease in AIDS patients: Excess mortality associated with high-dose clarithromycin

David L. Cohn, Evelyn J. Fisher, Grace T. Peng, James S Hodges, Jill Chesnut, Carroll C. Child, Barbara Franchino, Cynthia L. Gibert, Wafaa El-Sadr, Richard Hafner, Joyce Korvick, Mary Ropka, Leonid Heifets, Jan Clotfelter, David Munroe, C. Robert Horsburgh

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57 Scopus citations

Abstract

The optimal regimen for treatment of Mycobacterium avium complex (MAC) disease has not been established. Eighty-five AIDS patients with disseminated MAC disease were randomized to receive a three-drug regimen of clarithromycin, rifabutin or clofazimine, and ethambutol. Two dosages of clarithromycin, 500 or 1,000 mg twice daily (b.i.d.), were compared. The Data and Safety Monitoring Board recommended discontinuation of the clarithromycin dosage comparison and continuation of the rifabutin vs. clofazimine comparison. After a mean follow-up of 4.5 months, 10 (22%) of 45 patients receiving clarithromycin at 500 mg b.i.d. had died (70 deaths per 100 person- years) compared with 17 (43%) of 40 patients receiving clarithromycin at 1,000 mg b.i.d. (158 deaths per 100 person-years) (relative risk, 2.43; 95% confidence interval, 1.11-5.34; P = .02). After 10.4 months, 20 (49%) of 41 patients receiving rifabutin had died (81 deaths per 100 person-years) compared with 23 (52%) of 44 patients receiving clofazimine (94 deaths per 100 person-years) (relative risk, 1.20; 95% confidence interval, 0.65-2.19; P = .56). Bacteriologic outcomes were similar among treatment groups. In treating MAC disease in AIDS patients, the maximum dose of clarithromycin should be 500 mg b.i.d.

Original languageEnglish (US)
Pages (from-to)125-133
Number of pages9
JournalClinical Infectious Diseases
Volume29
Issue number1
DOIs
StatePublished - 1999

Bibliographical note

Funding Information:
Financial support: L.H. has received research grants and D.L.C. has received honoraria from Abbott Laboratories; L.H. has received research grants from and C.R.H. and D.L.C. have served as consultants to Pharmacia/Adria Laboratories. This study was supported by NIH (contracts AI-45228, AI-45234, AI-55258, AI-55255, AI-45224, AI-4040C, AI-45227, AI-45233, and AI-45220) and by Abbott Laboratories, Pharmacia/Adria Laboratories, Lederle Laboratories, and Ciba-Geigy Pharmaceuticals. * Present affiliation: U.S. Food and Drug Administration, Rockville, Maryland.

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