A cooperative trial on the primary prevention of ischaemic heart disease using clofibrate: design, methods, and...

The paper describes the design of, and the procedures used in a double blind randomized trial to determine whether the incidence of ischaemic heart disease can be lowered by the reduction of high and moderately high lipid levels in healthy men aged 30-59 years. The trial started in Edinburgh in 1965 and was extended to Prague and Budapest in 1966 and 1967. It is coordinated and controlled by a committee of investigators convened by the World Health Organization. The subjects were selected on the basis of a preliminary determination of serum cholesterol level. Half of the men in the upper third of the distribution of cholesterol values have been assigned at random to a treated group and take 1.6 g of clofibrate daily; the other half make up a control group and take identical capsules containing 300-350 mg of olive oil. A second control group, chosen at random from the lowest third of the cholesterol distribution, also receives the olive oil capsules. The study is designed to have a 90% chance of detecting, in the treated group, a reduction of one-third in the incidence of ischaemic heart disease if this should occur. The subjects are examined at the beginning of the trial, then at 6-month intervals for 2 years, and thereafter annually for at least 3 further years. The criteria of ischaemic heart disease are defined and the different control procedures are described. The required 15 000 subjects have now been admitted to the trial and their characteristics are described, but it is too early to report any results.