Cardiovascular DiseasesPhase 3UMPIRENCT01057537
UMPIRE - Use of a Multidrug Pill In Reducing Cardiovascular Events
A Phase 3 study testing polypill and Usual cardiovascular medications in people with Cardiovascular Diseases, run by Imperial College London at 7 sites in 5 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiovascular Diseases
- What is being tested?
- polypill and Usual cardiovascular medications
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,004 participants
- Where
- 7 sitesin 5 countries
- Study dates
- Jun 2010to Sep 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
India3 sites
George Institute for International Health - India
Hyderabad, 500033
Public Health Foundation of India
New Dehli, 110049
Centre for Chronic Disease Control
New Delhi, 110016
Ireland1 site
Royal College of Surgeons in Ireland Research Institute
Dublin, Dublin 9
Netherlands1 site
University Medical Center Utrecht
Utrecht, Heidelberglaan 100, 3584 CX
United Kingdom1 site
Clinical Investigation Unit, International Centre for Circulatory Health, Imperial College London
Paddington, London, W2 1LA
About this study
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.
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.
Read the 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
- Being tested
- polypill, Usual cardiovascular medications
- Keywords
- Polypill, Red Heart Pill, Cardiovascular disease, Adherence, Secondary prevention
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
polypillDrug
Also called Red Heart Pill
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 medicationsDrug
Also called Usual cardiovascular disease prevention medication
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.
| Study group | Role | What they receive |
|---|---|---|
| polypill | Experimental | 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. Receives: Drug: polypill |
| Usual Care | Active comparator | 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. Receives: Drug: Usual cardiovascular medications |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adherence to medication; self-reported current use of antiplatelet, statin and combination (≥ 2) blood pressure lowering therapy
Measured: End of trial follow-up
Change in blood pressure
Measured: End of trial follow-up
Change in LDL cholesterol
Measured: End of trial follow-up
Secondary outcomes (6)
Self reported current use of antiplatelet, statin and combination (>2) blood pressure lowering therapy
Measured: 12 months
Reasons for stopping cardiovascular medications
Measured: Throughout trial
Serious adverse events
Measured: Throughout trial
New onset cardiovascular events
Measured: Throughout trial
Participant 'Quality of Life' assessment
Measured: At 12 months and end of trial
Changes in total cholesterol and other lipid fractions (HDL-cholesterol, triglycerides)
Measured: 12 months and end of trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2010 (estimated)
- Study startJun 2010
- Primary completionJul 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,004 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- European Commission, Imperial College Healthcare NHS Trust, Royal College of Surgeons, Ireland, UMC Utrecht, The George Institute, Public Health Foundation of India, Dr. Reddy's Laboratories Limited
- Responsible party
- Sponsor
- Investigators
- Simon A McG Thom, MD, FRCP, Study director, Imperial College LondonNeil Poulter, Principal investigator, Imperial College LondonAnushka Patel, Principal investigator, The George Institute, IndiaDorairaj Prabhakaran, Principal investigator, Centre for Chronic Disease ControlMichiel Bots, Principal investigator, UMC UtrechtDiederick Grobbee, Principal investigator, UMC UtrechtAlice Stanton, Principal investigator, Royal College of Surgeons in IrelandAnthony Rodgers, Principal investigator, The George Institute, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01057537
- Sponsor's protocol ID
- 241849
- Other IDs
- 2009-016278-34, 2009
- Acronym
- UMPIRE
- Status last verified
- Nov 2012
- First submitted
- 26 Jan 2010
- Last updated
- 27 Nov 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 23038750Thom 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.
PubMed 24002278
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01057537
- Acronym / sponsor ID
- UMPIRE / 241849
- Conditions
- Cardiovascular Diseases
- Keywords
- Polypill, Red Heart Pill, Cardiovascular disease, Adherence, Secondary prevention
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,004 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- European Commission, Imperial College Healthcare NHS Trust, Royal College of Surgeons, Ireland, UMC Utrecht, The George Institute, Public Health Foundation of India, Dr. Reddy's Laboratories Limited
- Study start
- Jun 2010
- Primary completion
- Jul 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 27 Jan 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| polypill | Experimental | Drug: polypillRed 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. |
| Usual Care | Active comparator | Drug: Usual cardiovascular medicationsParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (4 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| polypillAlso: Red Heart PillThe 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. | Drug | polypill |
| Usual cardiovascular medicationsAlso: Usual cardiovascular disease prevention medicationParticipants 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. | Drug | Usual Care |
Primary outcome
Adherence to medication; self-reported current use of antiplatelet, statin and combination (≥ 2) blood pressure lowering therapy
Time frame: End of trial follow-up
Change in blood pressure
Time frame: End of trial follow-up
Change in LDL cholesterol
Time frame: End of trial follow-up
6 secondary outcomes
Self reported current use of antiplatelet, statin and combination (>2) blood pressure lowering therapy
Time frame: 12 months
Reasons for stopping cardiovascular medications
Time frame: Throughout trial
Serious adverse events
Time frame: Throughout trial
New onset cardiovascular events
Time frame: Throughout trial
Participant 'Quality of Life' assessment
Time frame: At 12 months and end of trial
Changes in total cholesterol and other lipid fractions (HDL-cholesterol, triglycerides)
Time frame: 12 months and end of trial
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2012.
- Background: PubMed 23038750Thom 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.
- Derived from this study: PubMed 24002278Thom 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.
- Single Pill to Avert Cardiovascular Events (SPACE) website for multinational polypill (RHP) trialsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Simon A McG Thom, MD, FRCP study director
Imperial College London
Neil Poulter principal investigator
Imperial College London
Anushka Patel principal investigator
The George Institute, India
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing polypill and Usual cardiovascular medications in people with Cardiovascular Diseases, run by Imperial College London at 7 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in India, Australia, Ireland, Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adherence to medication; self-reported current use of antiplatelet, statin and combination (≥ 2) blood pressure lowering therapy (time frame: End of trial follow-up). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01057537, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2012.