UMPIRE - Use of a Multidrug Pill In Reducing Cardiovascular Events

NCT ID: NCT01057537

Last Updated: 2012-11-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 2004 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2012-09-30

Brief Summary

People with established cardiovascular disease need secondary prevention that addresses multiple risk factors. Complexity & cost confer particularly difficult barriers to uptake of treatment; recovery from a stroke or heart attack typically necessitates multiple drugs for cholesterol, blood pressure and platelet function. A low-cost, fixed-dose, once-daily combination polypill, the Red Heart Pill, has been formulated by Dr Reddy's Laboratories. UMPIRE will evaluate whether provision of this polypill compared with usual medications improves adherence and clinical outcomes among high-risk patients in Europe and India. The results will be used to develop recommendations for equitable access.

Detailed Description

The UMPIRE trial has been modelled on similar trials running concurrently in Australia and New Zealand. The design is straight forward in making comparisons between cardiovascular preventative therapy delivered as a polypill (the Red Heart Pill) on the one hand, and as separate component multiple tablets (usual care) on the other hand. In both groups (the polypill group and the usual care group,) the GP or managing physician will be able to adjust or add additional medications as appropriate to meet the targets for control of blood pressure, cholesterol and other risk factors as directed by local or national guidelines. The Primary endpoint - adherence to prescribed cardiovascular preventative medication at the end of the trial follow-up - will be evaluated by self reported use of anti-platelet, statin and blood pressure lowering therapy. This evaluation will be supported by the recording of blood pressure and cholesterol levels, and measuring the differences between the two groups at the end of the trial. Treatment allocation is open label - both investigator and subject will know which arm of the study they are on. Patients will be identified and recruited from GP surgeries or hospital clinics, and also via local advertisement. Recruitment into the study is planned to start in Summer 2010 with a 12 month recruitment phase. Recruited subjects will spend between 12 - 30 months (average 18 months) being followed up. The target study population is 1000 patients in European at sites in London, Dublin and Utrecht; and 1000 subjects in India at approximately 30 sites. Subjects will be randomly allocated to receive either the "polypill" or "usual care". If allocated to the polypill group, the study investigator will decide on the version of polypill to be prescribed, and adjust any current medications as necessary. If the subject is in the "usual care" group, they will be seen as needed by their usual doctor between study visits, and continue on their current medicines. Participants will have at least 5 study visits, but no more than 8 study visits, and these visits include registration, randomisation and follow-up visits at 1 month, 6 months, and 12 months, and depending on when the subject is recruited to the study, study visits at 18 and 24 months/end of trial visit. A substudy, PESCA (Protocol ID CR01656, NCT01326676), will be performed in the European participants to assess whether the polypill reduces progression of atherosclerosis. This will be assessed by measuring carotid intima-medial thickness and central systolic blood pressure using the PulseCor device. A second substudy, INPUT, is a process evaluation involving qualitative interviews of a sample of health practitioners and trial participants at the end of the trial (summer 2012) in London and India.

Conditions

Cardiovascular Diseases

Keywords

Polypill; Red Heart Pill; Cardiovascular disease; Adherence; Secondary prevention

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

polypill

Red Heart Pill Version 1 and Red Heart Pill Version 2. In general, participants with a history of coronary heart disease will be given version 1, and those with a history of stroke or cerebrovascular disease will be given version 2.

Group Type: EXPERIMENTAL

polypill

Intervention Type: DRUG

The polypill will be taken once/day in the form of a hard capsule, to be taken orally. There are two versions of the polypill (Red Heart Pill):

Version 1 contains aspirin 75mg, simvastatin 40mg, Lisinopril 10mg and Atenolol 50mg; Version 2 contains aspirin 75mg, simvastatin 40mg, Lisinopril 10mg and Hydrochlorothiazide 12.5mg.

Usual Care

Participants in the usual care arm will take their usual cardiovascular medications. The participants will be seen as needed by their usual doctor between study visits.

Group Type: ACTIVE_COMPARATOR

Usual cardiovascular medications

Intervention Type: DRUG

Participants in the 'Usual Care' arm will continue to take the separate, individual medications prescribed by their usual doctor, e.g. aspirin, blood pressure lowering drugs, statins.

Interventions

polypill

The polypill will be taken once/day in the form of a hard capsule, to be taken orally. There are two versions of the polypill (Red Heart Pill):

Version 1 contains aspirin 75mg, simvastatin 40mg, Lisinopril 10mg and Atenolol 50mg; Version 2 contains aspirin 75mg, simvastatin 40mg, Lisinopril 10mg and Hydrochlorothiazide 12.5mg.

Intervention Type: DRUG

Usual cardiovascular medications

Participants in the 'Usual Care' arm will continue to take the separate, individual medications prescribed by their usual doctor, e.g. aspirin, blood pressure lowering drugs, statins.

Intervention Type: DRUG

Other Intervention Names

Red Heart Pill; Usual cardiovascular disease prevention medication

Eligibility Criteria

Inclusion Criteria

• Adults (≥ 18 years)
• The participant is able to give informed consent.
• Established atherothrombotic cardiovascular disease (CVD) or high cardiovascular risk, of for individuals without established cardiovascular disease, a calculated 5 year CVD risk of 15% or greater (calculated using the 1991 Anderson Framingham risk equation with adjustments as defined by the New Zealand Guidelines Group recommendations)
• The trial Investigator considers that each of the polypill components are indicated
• The trial Investigator is unsure as to whether a polypill-based strategy or usual care is better.

Exclusion Criteria

• Contraindication to any of the components of the polypill (e.g. known intolerance to aspirin, statins, or ACE inhibitors,pregnancy or likely to become pregnant during the treatment period).
• The treating doctor considers that changing a participant's cardiovascular medications would put the participant at risk (e.g. symptomatic heart failure, high dose βblocker required to manage angina or for rate control in atrial fibrillation,accelerated hypertension, severe renal insufficiency, a history of severe resistant hypertension)
• Known situation where medication regimen might be altered for a significant length of time, e.g. current acute cardiovascular event, planned coronary bypass graft operation.
• Unlikely to complete the trial (e.g. lifethreatening condition other than cardiovascular disease) or adhere to the trial procedures or attend study visits (e.g. major psychiatric condition, dementia).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Commission

OTHER

Sponsor Role: collaborator

Imperial College Healthcare NHS Trust

OTHER

Sponsor Role: collaborator

Royal College of Surgeons, Ireland

OTHER

Sponsor Role: collaborator

UMC Utrecht

OTHER

Sponsor Role: collaborator

The George Institute

OTHER

Sponsor Role: collaborator

Public Health Foundation of India

OTHER

Sponsor Role: collaborator

Dr. Reddy's Laboratories Limited

INDUSTRY

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Simon A McG Thom, MD, FRCP

Role: STUDY_DIRECTOR

Imperial College London

Neil Poulter

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Anushka Patel

Role: PRINCIPAL_INVESTIGATOR

The George Institute, India

Dorairaj Prabhakaran

Role: PRINCIPAL_INVESTIGATOR

Centre for Chronic Disease Control

Michiel Bots

Role: PRINCIPAL_INVESTIGATOR

UMC Utrecht

Diederick Grobbee

Role: PRINCIPAL_INVESTIGATOR

UMC Utrecht

Alice Stanton

Role: PRINCIPAL_INVESTIGATOR

Royal College of Surgeons in Ireland

Anthony Rodgers

Role: PRINCIPAL_INVESTIGATOR

The George Institute, Australia

Raghu Cidambi

Role: PRINCIPAL_INVESTIGATOR

Dr. Reddy's Laboratories Limited

K Srinath Reddy

Role: PRINCIPAL_INVESTIGATOR

Public Health Foundation of India

Locations

George Institute Australia

Sydney, New South Wales, Australia

George Institute for International Health - India

Hyderabad, , India

Public Health Foundation of India

New Dehli, , India

Centre for Chronic Disease Control

New Delhi, , India

Royal College of Surgeons in Ireland Research Institute

Dublin, , Ireland

University Medical Center Utrecht

Utrecht, Heidelberglaan 100, Netherlands

Clinical Investigation Unit, International Centre for Circulatory Health, Imperial College London

Paddington, London, United Kingdom

Countries

Australia; India; Ireland; Netherlands; United Kingdom

References

Thom S, Field J, Poulter N, Patel A, Prabhakaran D, Stanton A, Grobbee DE, Bots ML, Reddy KS, Cidambi R, Rodgers A. Use of a Multidrug Pill In Reducing cardiovascular Events (UMPIRE): rationale and design of a randomised controlled trial of a cardiovascular preventive polypill-based strategy in India and Europe. Eur J Prev Cardiol. 2014 Feb;21(2):252-61. doi: 10.1177/2047487312463278. Epub 2012 Oct 4.

Reference Type: BACKGROUND

PMID: 23038750 (View on PubMed)

Thom S, Poulter N, Field J, Patel A, Prabhakaran D, Stanton A, Grobbee DE, Bots ML, Reddy KS, Cidambi R, Bompoint S, Billot L, Rodgers A; UMPIRE Collaborative Group. Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial. JAMA. 2013 Sep 4;310(9):918-29. doi: 10.1001/jama.2013.277064.

Reference Type: DERIVED

PMID: 24002278 (View on PubMed)

Related Links

http://www.spacecollaboration.org

Single Pill to Avert Cardiovascular Events (SPACE) website for multinational polypill (RHP) trials

Other Identifiers

2009-016278-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

241849

Identifier Type: -

Identifier Source: org_study_id