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The International Polycap Study 3 (TIPS-3) (TIPS-3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01646437
Recruitment Status : Active, not recruiting
First Posted : July 20, 2012
Last Update Posted : September 30, 2019
Cadila Pharnmaceuticals
Wellcome Trust
Canadian Institutes of Health Research (CIHR)
Heart and Stroke Foundation of Ontario
Information provided by (Responsible Party):
Salim Yusuf's office, Population Health Research Institute

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.

Condition or disease Intervention/treatment Phase
Cardiovascular Disease Fractures Cancers Drug: Polycap Drug: Aspirin Drug: Vitamin D Drug: Matching Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5713 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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
Study Start Date : June 2012
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin D

Arm Intervention/treatment
Experimental: Polycap vs. matching placebo
Polycap is a once daily capsule containing thiazide (25mg), atenolol (100mg), ramipril (10mg) and simvastatin (40mg) vs. matching placebo
Drug: Polycap
Polycap (thiazide 25mg, atenolol 100mg, ramipril 10mg, simvastatin 40mg) taken once daily

Drug: Matching Placebo
Matching Placebo

Experimental: Aspirin vs. matching placebo
Once daily 75mg tablet of Aspirin vs. matching placebo
Drug: Aspirin
75 mg daily
Other Name: enteric coated aspirin

Drug: Matching Placebo
Matching Placebo

Experimental: Vitamin D vs. matching placebo
Monthly oral dosage of 60,000IU vs. matching placebo
Drug: Vitamin D
60,000 IU monthly
Other Name: cholecalciferol

Drug: Matching Placebo
Matching Placebo

Primary Outcome Measures :
  1. Composite of major CVD (CV death, non-fatal stroke, non-fatal MI), plus heart failure, resuscitated cardiac arrest, or revascularization with evidence of ischemia in participants taking Polycap versus placebo [ Time Frame: Particpants will be followed for an average of 5 years ]
  2. Composite of CV events (CV death, MI or stroke) and cancer in participants taking aspirin versus placebo [ Time Frame: Participants will be followed for an average of 5 years ]
  3. Risk of fractures in participants taking vitamin D versus placebo [ Time Frame: Participants will be followed for an average of 5 years ]

Secondary Outcome Measures :
  1. Composite of CV death, non-fatal stroke, and nonfatal MI in participants taking Polycap versus placebo [ Time Frame: Participants will be followed for an average of 5 years ]
  2. Composite outcome of CV events and cancers after 10 years of follow up in participants taking aspirin versus placebo [ Time Frame: Participants will be followed for 10 years ]
  3. Composite outcome of CV events, fractures and cancers, and the risk of the falls at 10 years of follow up in participants taking vitamin D versus placebo [ Time Frame: Participants will be followed for 10 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Men aged ≥ 55 years and women aged ≥ 60 years with and INTERHEART risk score of 10 or greater
  • 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/day
  • Hypercalcemia, hyperparathyroidism, osteomalacia or other contraindication or indication for vitamin D therapy
  • Peptic ulcer disease, frequent dyspepsia or bleeding
  • Known vascular disease. (e.g. Stroke, TIA, Angina, MI, ACS, PVD including claudication and amputation)
  • Mean systolic BP 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01646437

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Dhaka, Bangladesh
Canada, Ontario
Hamilton Health Sciences
Hamilton, Ontario, Canada, L8L 2X2
Fundaction Oftamologica De Santander (FOSCAL)
Bucaramanga, Colombia
St. John's Medical College Hospital
Bangalore, India
Centre For Translational Research & Epidemiology (CenTRE)
Selangor, Malaysia
Adult Medicine & Medical Research Unit, Philippine General Hospital
Manila, Philippines
Pamoja Tunaweza Women's Centre
Moshi, Tanzania
Fattouma Bourguiba University Hospital
Monastir, Tunisia
Sponsors and Collaborators
Population Health Research Institute
Cadila Pharnmaceuticals
Wellcome Trust
Canadian Institutes of Health Research (CIHR)
Heart and Stroke Foundation of Ontario
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Principal Investigator: Salim Yusuf Population Health Research Institute
Principal Investigator: Prem Pais St. John's Research Institute
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Salim Yusuf's office, Executive Director - Population Health Research Institute, Professor of Medicine - McMaster University, Population Health Research Institute Identifier: NCT01646437    
Other Study ID Numbers: TIPS-3
First Posted: July 20, 2012    Key Record Dates
Last Update Posted: September 30, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Cardiovascular Diseases
Vitamin D
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Calcium-Regulating Hormones and Agents