UMPIRE - Use of a Multidrug Pill In Reducing Cardiovascular Events

Cardiovascular Diseases Clinical Trial

— UMPIRE  

Official title:

A Randomised Controlled Trial of a Fixed-dose Combination Polypill Medication (the Red Heart Pill) and Usual Care in Those at High Risk of Cardiovascular Disease.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01057537
• Other study ID #: 241849
• Secondary ID: 2009-016278-34
• Status: Completed
• Phase: Phase 3
• First received: January 26, 2010
• Last updated: November 26, 2012
• Start date: June 2010
• Est. completion date: September 2012

Study information

• Verified date: November 2012
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kngdom: Medicines and Healthcare products Regulatory Agency (MHRA)Ireland: Irish Medicines Board (IMB)The Netherlands: Dutch Healthcare Inspectorate (CCMO)India: Drugs Controller General, India (DCGI)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2004
• Est. completion date: September 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 ßblocker 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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Diseases

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
Australia	George Institute Australia	Sydney	New South Wales
India	George Institute for International Health - India	Hyderabad
India	Public Health Foundation of India	New Dehli
India	Centre for Chronic Disease Control	New Delhi
Ireland	Royal College of Surgeons in Ireland Research Institute	Dublin
Netherlands	University Medical Center Utrecht	Utrecht	Heidelberglaan 100
United Kingdom	Clinical Investigation Unit, International Centre for Circulatory Health, Imperial College London	Paddington	London

Sponsors (8)

Lead Sponsor	Collaborator
Imperial College London	Dr. Reddy's Laboratories Limited, European Commission, Imperial College Healthcare NHS Trust, Public Health Foundation of India, Royal College of Surgeons, Ireland, The George Institute, UMC Utrecht

Countries where clinical trial is conducted

Australia,  India,  Ireland,  Netherlands,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adherence to medication; self-reported current use of antiplatelet, statin and combination (= 2) blood pressure lowering therapy		End of trial follow-up	Yes
Primary	Change in blood pressure		End of trial follow-up	Yes
Primary	Change in LDL cholesterol		End of trial follow-up	Yes
Secondary	Self reported current use of antiplatelet, statin and combination (>2) blood pressure lowering therapy		12 months	Yes
Secondary	Reasons for stopping cardiovascular medications		Throughout trial	Yes
Secondary	Serious adverse events		Throughout trial	Yes
Secondary	New onset cardiovascular events		Throughout trial	Yes
Secondary	Participant 'Quality of Life' assessment		At 12 months and end of trial	No
Secondary	Changes in total cholesterol and other lipid fractions (HDL-cholesterol, triglycerides)		12 months and end of trial	Yes

External Links

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