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A randomized, double-blind study (561) compared clarithromycin 500 mg b.i.d. to placebo in patientswith CDC-defined AIDS and CD4 counts less than 100 cells/µL. This study accrued 682 patients fromNovember 1992 to January 1994, with a median CD4 cell count at study entry of 30 cells/µL. Medianduration of clarithromycin was 10.6 months vs. 8.2 months for placebo. More patients in the placeboarm than the clarithromycin arm discontinued prematurely from the study (75.6% and 67.4%,respectively). However, if premature discontinuations due to MAC or death are excluded,approximately equal percentages of patients on each arm (54.8% on clarithromycin and 52.5% onplacebo) discontinued study drug early for other reasons. The study was designed to evaluate thefollowing endpoints:
- MAC bacteremia, defined as at least one positive culture for M. avium complex bacteria from blood or another normally sterile site.
- Clinically significant disseminated MAC disease, defined as MAC bacteremia accompanied by signs or symptoms of serious MAC infection, including fever, night sweats, weight loss, anemia, or elevations in liver function tests.
In patients randomized to clarithromycin, the risk of MAC bacteremia was reduced by 69% compared to placebo. The difference between groups was statistically significant (p less than 0.001). On an intent-to-treat basis, the one-year cumulative incidence of MAC bacteremia was 5.0% for patients randomized to clarithromycin and 19.4% for patients randomized to placebo. While only 19 of the 341 patients randomized to clarithromycin developed MAC, 11 of these cases were resistant to clarithromycin. The patients with resistant MAC bacteremia had a median baseline CD4 count of 10 cells/mm3 (range 2 to 25 cells/mm3). Information regarding the clinical course and response to treatment of the patients with resistant MAC bacteremia is limited. The 8 patients who received clarithromycin and developed susceptible MAC bacteremia had a median baseline CD4 count of 25 cells/mm3 (range 10 to 80 cells/mm3). Comparatively, 53 of the 341 placebo patients developed MAC; none of these isolates were resistant to clarithromycin. The median baseline CD4 count was 15 cells/mm3 (range 2 to 130 cells/mm3) for placebo patients that developed MAC.
Survival A statistically significant survival benefit was observed.
Survival All Randomized Patients
Mortality Placebo Clarithromycin Reduction in Mortality on Clarithromycin 6 month 9.4% 6.5% 31% 12 month 29.7% 20.5% 31% 18 month 46.4% 37.5% 20%
Since the analysis at 18 months includes patients no longer receiving prophylaxis the survival benefit of clarithromycin may be underestimated.
Clinically Significant Disseminated MAC Disease
In association with the decreased incidence of bacteremia, patients in the group randomized toclarithromycin showed reductions in the signs and symptoms of disseminated MAC disease, includingfever, night sweats, weight loss, and anemia.
- Drug Information Provided by National Library of Medicine (NLM).