The International Programme to evaluate the Polycap in a large randomised controlled clinical trial in a primary prevention setting.

We have completed the world's largest study comparing different formulations of the Polycap, and demonstrated efficacy and feasibility (appendix 3, Lancet March 30th 2009). We intend to carry out two further studies, (1) to evaluate a full dose Polycap for safety in high risk individuals (eg secondary prevention), and (2) to conduct a large study (5000 subjects without CVD) using the current formulation (but without aspirin) to assess the clinical benefit of the Polycap . In the Indian Polycap study (TIPS) we evaluated the impact of the Polycap (without folic acid) on BP, lipids, heart rate and urinary thromboxane B2 and tolerability in 2053 individuals without CVD and average risk factor levels. The Polycap was well tolerated and reduced BP, LDL, heart rate and urinary thromboxane B2 excretion to the same extent as the comparators. The degree of reduction in risk factors suggests that the Polycap could potentially reduce coronary heart disease (CHD) risk by 62% and stroke by 48%. We now propose to conduct a large clinical outcomes trial of the Polycap versus placebo in 5,000 individuals from India and China in men over 55 yrs and women over 60 yrs with a INTERHEART risk score >12. The Primary Outcome is a composite of CV death, non-fatal MI, and non-fatal stroke. With 5,000 individuals followed up for a mean of about 5 years (estimated yearly primary event rate of 0.75 to 1% in the placebo group, we will have 80 to 90% power to detect 40 to 50% relative risk reductions.