The International Polycap Study 3 (TIPS-3) is a Randomized Double-blind Placebo-controlled Trial for the Evaluation of a Polycap, Low Dose Aspirin and Vitamin D Supplementation in Primary Prevention
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 7,793
- Locations
- 9
- Primary Endpoint
- Vitamin D Primary Objective
Study Overview
Brief Summary
The randomized 2x2x2 factorial design placebo controlled trial will enroll 5000 participants (women 60 years or older and men 55 years or older) without known heart disease or prior stroke and without a clear indication or contraindication to any of the study medications. Eligible and consenting individuals will be randomized to receive either the active study medications or placebo (dummy pills) and will be monitored for an average of 5 years. The study will include people from at 10 countries, will be conducted by an international group of scientists and physicians and will be coordinated by the Population Health Research Institute at Hamilton Health Sciences.
Detailed Description
Cardiovascular disease (CVD), cancers and osteoporosis collectively make up the largest disease burden globally. CVD is the major cause of death and disability and affects about half of the population over their lifetimes. Cancers are a leading cause of death and it accounts for 13.0% of all deaths. The commonest forms include lung, breast, prostate, colorectum, stomach and liver cancer. It is estimated that over 200 hundred million people worldwide are living with osteoporosis. This is the underlying pathologic predisposition to fractures of the hip, vertebral body, and distal forearm. CVD, cancers and osteoporotic fractures increase with age and so their burden is expected to substantially increase over the next few decades. Simple, safe and effective preventive strategies which can reduce the incidence and prevalence of these 3 diseases are therefore urgently needed
It is suggested that this polypill could be given to all individuals with a CVD event as well as to anyone over 55 years (primary prevention) without the need for any measurement of risk factors. The polypill contains 3 blood pressure lowing medications and a statin in a single tablet. This includes hydrochlorothiazide (25 mg), atenolol (100 mg), ramipril (10 mg) and simvastatin (40 mg). In addition, to the polypill (Polycap), participants will be randomized to receive aspirin (75mg) and vitamin D (60,000 IU monthly). This factorial design on 3 distinct treatment arms which could reduce CVD, fractures and cancers could have large implications for the prevention of several of the important chronic diseases in middle and old age, using safe and inexpensive medications/supplements.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 50 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Men aged ≥ 50 years and women aged ≥ 55 years with an INTERHEART risk score ≥ 10 OR men and women aged ≥ 65 years with an INTERHEART risk score of ≥
- •Provision of informed consent
- •Exclusion Criteria
- •Participants with a clear clinical indication, contraindication, preference for or intolerance to statin, beta blocker (e.g. bradycardia), ACE inhibitor, diuretic, aspirin or clopidogrel in the judgment of the physician.
- •Regular use of vitamin D at doses higher than 400 IU per day.
- •Hypercalcemia, hyperparathyroidism, osteomalacia or other contraindication or indication for vitamin D therapy.
- •Peptic ulcer disease, frequent dyspepsia or bleeding.
- •Expected long term use of anticoagulants
- •Known vascular disease. (e.g., Stroke, TIA, Angina, MI, ACS, PVD including claudication and amputation).
- •Mean systolic BP (using 2 automatic readings) below 120 mm Hg at run-in.
- •Symptomatic hypotension (e.g., dizziness with SBP <110 mm Hg systolic) during the run-in phase.
- •Chronic liver disease or abnormal liver function, i.e. ALT or AST > 3 x ULN.
- •Inflammatory muscle disease (such as dermatomyositis or polymyositis) or creatine kinase (CK) > 3 x ULN.
- •Severe renal impairment (serum creatinine >264 µmol/L).
- •History of malignancy affecting any organ system, except basal cell carcinoma of the skin, within the previous 5 years.
- •Other serious condition(s) likely to interfere with study participation or with the ability to complete the trial.
- •Concurrent use of any experimental pharmacological agent.
- •Inability to attend follow-up as required by the protocol for at least 5 years.
Exclusion Criteria
- Not provided
Arms & Interventions
Vitamin D vs. matching placebo
Monthly oral dosage of 60,000IU vs. matching placebo
Intervention: Vitamin D (Drug)
Vitamin D vs. matching placebo
Monthly oral dosage of 60,000IU vs. matching placebo
Intervention: Matching Placebo (Drug)
Polycap vs. matching placebo
Polycap is a once daily capsule containing thiazide (25mg), atenolol (100mg), ramipril (10mg) and simvastatin (40mg) vs. matching placebo
Intervention: Polycap (Drug)
Polycap vs. matching placebo
Polycap is a once daily capsule containing thiazide (25mg), atenolol (100mg), ramipril (10mg) and simvastatin (40mg) vs. matching placebo
Intervention: Matching Placebo (Drug)
Aspirin vs. matching placebo
Once daily 75mg tablet of Aspirin vs. matching placebo
Intervention: Aspirin (Drug)
Aspirin vs. matching placebo
Once daily 75mg tablet of Aspirin vs. matching placebo
Intervention: Matching Placebo (Drug)
Outcomes
Primary Outcomes
Vitamin D Primary Objective
Time Frame: Participants will be followed for an average of 4.25 years
To determine whether vitamin D reduces the risk of fractures compared to its placebo.
Combined Effects of Polycap and Aspirin on CVD Events
Time Frame: Participants will be followed for an average of 4.25 years
To determine the combined effect of aspirin and the Polycap (i.e. double treatment) on major CV events (CV death, non-fatal MI or non-fatal stroke), heart failure, resuscitated cardiac arrest, or arterial revascularization compared to double-placebo.
Aspirin Primary Objective
Time Frame: Participants will be followed for an average of 4.25 years
To determine whether aspirin reduces the risk of composite outcome of major CV events (CV death, non-fatal MI or non-fatal stroke,) compared to its placebo.
Polycap Primary Objective
Time Frame: Participants will be followed for an average of 4.25 years
To determine whether the Polycap reduces the risk of the composite outcome of CVD events which includes major CVD (CV death, non-fatal stroke, non-fatal MI), plus heart failure, resuscitated cardiac arrest, or arterial revascularization compared to placebo.
Secondary Outcomes
- Vitamin D Secondary Objective(Participants will be followed for an average of 4.25 years)
- Combined Effects of Polycap and Aspirin on CVD Events Secondary Outcome A(Participants will be followed for an average of 4.25 years)
- Aspirin Secondary Objective(Participants will be followed for an average of 4.25 years)
- Polycap Secondary Objective(Participants will be followed for an average of 4.25 years)
- Combined Effects of Polycap and Aspirin on CVD Events Secondary Outcome B(Participants will be followed for an average of 4.25 years)
Investigators
Salim Yusuf's office
Executive Director - Population Health Research Institute, Professor of Medicine - McMaster University
Population Health Research Institute