TIPS-3 - The International Polycap Study 3


Overview


The International Polycap Study 3 (TIPS-3) is a randomized double-blind placebo-controlled trial for the evaluation of Polycap (a single pill containing multiple medications), low dose aspirin and vitamin D supplementation in primary prevention of cardiovascular disease, cancer and fractures. Led by co-investigators Dr. Salim Yusuf of McMaster University and Dr. Prem Pais of St. John's Medical College and Research Institute in Bangalore, India, the study will be conducted in 11 countries and aims to recruit over 5000 participants. The study is coordinated and sponsored by the Population Health Research Institute, McMaster University and Hamilton Health Sciences, in collaboration with research teams at each of the study sites. The Vancouver site, run through St. Paul's Hospital, is lead by CoHeaRT's Dr. Scott Lear and Dr. Carolyn Taylor, cardiologist at the University of British Columbia and St. Paul's Healthy Heart Program.


Background


Cardiovascular diseases (CVD) are a major cause of death worldwide1, and we urgently need to develop effective preventive strategies. The preferred population-based strategy is to implement policy-level changes that can reduce tobacco use and improve nutrition and physical activity levels. While these strategies will likely take time to develop over the next few decades, a more immediate approach is to modify the major risk factors for CVD using combinations of simple, proven, safe, widely available and inexpensive drugs. This approach has been the basis for the development of "the polypill concept" as a complementary strategy to other ongoing efforts at primary and secondary prevention.

It has been proposed that a combination of aspirin, statins, beta-blockers and ACE inhibitors in a single pill could reduce subsequent CVD events by 75% in those who already have clinical CVD2. It has also been suggested that a "polypill" with a statin, plus 3 half-doses of a thiazide, beta-blocker, and ACE- inhibitor could reduce the risk of CVD by as much as 80%3. In TIPS-3, the Polycap contains thiazide (diuretic), atenolol (beta-blocker), ramipril (ACE inhibitor), and simvastatin (statin). The trial will also separately dispense daily low dose aspirin and monthly vitamin D to investigate their effects on CVD, cancer and osteoperosis. The results of this study could have large implications for the prevention of several of the important chronic diseases in middle and old age, using safe and inexpensive treatments.


Objectives


1. To determine whether the Polycap reduces the risk of CVD events (including CV death, non-fatal stroke, non-fatal heart attacks, heart failure, resuscitated cardiac arrest, or revascularization with evidence of ischemia) compared to placebo.

2. To determine whether aspirin reduces the risk of CV events and cancers and whether vitamin D reduces the risk of fractures.


Methodology


The trial will randomize at least 5000 study participants through the various study sites and expects to see at least 250 primary CVD outcome events. Eligible participants include women 55 years or older and men 50 years or older with an INTERHEART risk score of ≥ 10, without known heart disease or prior stroke and without a clear indication or contraindication to any of the study medications. Through an 8-arm trial design, consenting individuals will receive either the active study medications (Polycap,+/- aspirin, +/- monthly vitamin D) or the placebo equivalents (dummy pills). Participants will be monitored for 5 years and will undergo passive follow-ups for an additional 5 years. Our site will be recruiting approximately 150 - 200 participants from the existing PURE Study pool.


Progress to Date


The study is currently recruiting participants from the PURE Study.


References


  1. The World Health Report 2004. Deaths by cause, sex and mortality stratum in WHO regions, estimates for 2002.
  2. Yusuf S. Two decades of progress in preventing vascular disease. Lancet 2002; 360:2-3.
  3. Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003;326:1419-1424.