WIZARD and the design of trials for secondary prevention of atherosclerosis with antibiotics.

Clinical trials to assess the merit of antibiotic intervention in the treatment of ischemic cardiovascular disease are now underway, spurred on by an association between Chlamydia pneumoniae and atherogenesis noted in epidemiologic investigations, histopathologic studies, and results from various animal models. The design of such clinical trials must take into account a number of issues: the primary event as strictly defined by objective criteria, the event rate in the chosen population, the potential treatment effect, the availability of patients, the underlying cause of their atherosclerotic disease, the determination of the C pneumoniae-infected population to study, the dose and duration of the antibiotic, and the length of follow-up. In the design of the WIZARD study (Weekly Intervention with Zithromax for Atherosclerosis and its Related Disorders), an attempt was made to take these issues under consideration. Patients were randomly assigned either to 600 mg/d zithromax for 3 days then 600 mg/wk for 11 additional weeks or to placebo. Patients in the study had a myocardial infarction at least 6 weeks previously, had no recent coronary artery bypass graft or percutaneous transluminal coronary angioplasty, and did not required long-term administration of antibiotics. Patients were required to have an immunoglobulin G titer to C pneumoniae of >/=1:16. The primary end point was the time to a composite of all-cause death, myocardial infarction, a revascularization procedure, or hospitalization for angina. The study enrolled 3500 patients, sufficient to detect a 25% reduction in the presumed 8% placebo event rate with 90% power. Follow-up will continue through the prespecified number of end points.

RCT Entities:   Population Interventions Outcomes