Clinical trials to assess the merit of antibiotic intervention in the treat
ment of ischemic cardiovascular disease are now underway, spurred on by an
association between Chlamydia pneumoniae and atherogenesis noted in epidemi
ologic investigations, histopathologic studies, and results from various an
imal models. The design of such clinical trials must take into account a nu
mber 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 stud
y, 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 Ath
erosclerosis and its Related Disorders), an attempt was made to take these
issues under consideration. Patients were randomly assigned either to 600 m
g/d zithromax for 3 days then 600 mg/wk for 11 additional weeks or to place
bo. Patients in the study had a myocardial infarction at least 6 weeks prev
iously, had no recent coronary artery bypass graft or percutaneous translum
inal coronary angioplasty, and did not required long-term administration of
antibiotics. Patients were required to have an immunoglobulin G titer to C
pneumoniae of greater than or equal to 1:16. The primary end point was the
time to a composite of all-cause death, myocardial infarction, a revascula
rization procedure, or hospitalization for angina, the study enrolled 3500
patients, sufficient to detect a 25% reduction in the presumed 8% placebo e
vent rate with 90% power. Follow-up will continue through the prespecified
number of end points.