The International Polycap Study 3 (TIPS-3)

Population Health Research Institute (PHRI)

Status and phase: Completed; Phase 3

Conditions: Fractures; Cancers; Cardiovascular Disease

Treatments: Drug: Vitamin D; Drug: Matching Placebo; Drug: Aspirin; Drug: Polycap

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01646437

TIPS-3

Details and patient eligibility

About

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.

Full 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.

Enrollment: 7,793 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 ≥5.
• 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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7,793 participants in 3 patient groups

Polycap vs. matching placebo

Experimental group

Description:

Polycap is a once daily capsule containing thiazide (25mg), atenolol (100mg), ramipril (10mg) and simvastatin (40mg) vs. matching placebo

Treatment:

Drug: Polycap

Drug: Matching Placebo

Aspirin vs. matching placebo

Experimental group

Description:

Once daily 75mg tablet of Aspirin vs. matching placebo

Treatment:

Drug: Aspirin

Drug: Matching Placebo

Vitamin D vs. matching placebo

Experimental group

Description:

Monthly oral dosage of 60,000IU vs. matching placebo

Treatment:

Drug: Vitamin D

Drug: Matching Placebo