The International Polycap Study 3 (TIPS-3)

Cardiovascular Disease Clinical Trial

— TIPS-3  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01646437
• Other study ID #: TIPS-3
• Status: Completed
• Phase: Phase 3
• Start date: June 2012
• Est. completion date: August 30, 2021

Study information

• Verified date: September 2021
• Source: Population Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7793
• Est. completion date: August 30, 2021
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cancers
• Cardiovascular Disease
• Cardiovascular Diseases
• Fractures

Intervention

Drug:
• Polycap
Polycap (thiazide 25mg, atenolol 100mg, ramipril 10mg, simvastatin 40mg) taken once daily
• Aspirin
75 mg daily
• Vitamin D
60,000 IU monthly
• Matching Placebo
Matching Placebo

Locations

Country	Name	City	State
Bangladesh	Eminence	Dhaka
Canada	Hamilton Health Sciences	Hamilton	Ontario
Colombia	Fundaction Oftamologica De Santander (FOSCAL)	Bucaramanga
India	St. John's Medical College Hospital	Bangalore
Indonesia	Harapan Kita Hopsital	Jakarta
Malaysia	Universiti Teknologi MARA (UiTM)	Shah Alam	Selangor
Philippines	Adult Medicine & Medical Research Unit, Philippine General Hospital	Manila
Tanzania	Pamoja Tunaweza Women's Centre	Moshi
Tunisia	Fattouma Bourguiba University Hospital	Monastir

Sponsors (5)

Lead Sponsor	Collaborator
Population Health Research Institute	Cadila Pharnmaceuticals, Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation of Ontario, Wellcome Trust

Countries where clinical trial is conducted

Bangladesh,  Canada,  Colombia,  India,  Indonesia,  Malaysia,  Philippines,  Tanzania,  Tunisia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Total mortality	To assess the effect of each of the 3 treatments on total mortality.	Participants will be followed for an average of 4.25 years
Other	Incident and recurrent CV events	To determine whether the Polycap reduces the risk of incident and recurrent CV events (which is comprised of major CVD (CV death, non- fatal stroke, non-fatal myocardial infarction [MI]), plus heart failure, resuscitated cardiac arrest or arterial revascularization)).	Participants will be followed for an average of 4.25 years
Other	Long term safety	To assess the long-term safety of each treatment (Polycap, Aspirin or Vitamin D) versus their respective placebo on safety and tolerability.	Participants will be followed for an average of 4.25 years
Other	Visual acuity	To assess the effect of the Polycap and Aspirin on visual acuity change from baseline and onset of age-related macular degeneration.	Participants will be followed for an average of 4.25 years
Other	Cognitive Function	To assess the effect of each of the 3 treatments on cognitive function	Participants will be followed for an average of 4.25 years
Other	Health Economics	To assess the economic impact of the Polycap	Participants will be followed for an average of 4.25 years
Primary	Polycap Primary Objective	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.	Participants will be followed for an average of 4.25 years
Primary	Aspirin Primary Objective	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.	Participants will be followed for an average of 4.25 years
Primary	Vitamin D Primary Objective	To determine whether vitamin D reduces the risk of fractures compared to its placebo.	Participants will be followed for an average of 4.25 years
Primary	Combined Effects of Polycap and Aspirin on CVD Events	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.	Participants will be followed for an average of 4.25 years
Secondary	Polycap Secondary Objective	To determine whether the Polycap reduces the risk of the composite of CV death, non-fatal stroke, and non-fatal MI compared to its placebo.To determine whether the Polycap reduces the risk of the composite outcome of major CVD (CV death, non- fatal stroke, non-fatal myocardial infarction [MI]), heart failure, resuscitated cardiac arrest, arterial revascularization, or angina with evidence of ischemia.	Participants will be followed for an average of 4.25 years
Secondary	Aspirin Secondary Objective	To determine whether a daily aspirin reduces the risk of the composite outcome of major CV events (CV death, non-fatal MI or non-fatal stroke) and cancers compared to its placebo.	Participants will be followed for an average of 4.25 years
Secondary	Vitamin D Secondary Objective	To determine whether vitamin D reduces the risk of the composite outcome of CV events, fractures and cancers, and the risk of falls compared to its placebo.	Participants will be followed for an average of 4.25 years
Secondary	Combined Effects of Polycap and Aspirin on CVD Events Secondary Outcome A	To determine whether the Polycap and aspirin reduces the risk of the composite of CV death, non-fatal stroke, and non-fatal MI compared to double placebo.	Participants will be followed for an average of 4.25 years
Secondary	Combined Effects of Polycap and Aspirin on CVD Events Secondary Outcome B	To determine whether the Polycap and aspirin reduces the risk of the composite outcome of major CVD (CV death, non- fatal stroke, non-fatal myocardial infarction [MI]), heart failure, resuscitated cardiac arrest, arterial revascularization, or angina with evidence of ischemia, compared to double-placebo	Participants will be followed for an average of 4.25 years