Condition category
Circulatory System
Date applied
22/05/2014
Date assigned
25/07/2014
Last edited
31/07/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Optimal therapy for people who have had a stroke or a Transient Ischaemic Attack (TIA) consists of blood pressure (BP) lowering, cholesterol lowering and anti-platelet agents to reduce risk of further cerebrovascular events. Survey data continue to show that guidelines for secondary prevention of cardiovascular events are not well implemented in clinical practice. This is a worldwide phenomenon, more common in elderly patients. An alternative to traditional ‘treat to target’ approaches is to adopt simpler regimes such as using a fixed dose combination (FDC) pill. The aim of this study is to test whether such a regime will be non-inferior to standard care. The rationale for such a regime is that it will: reduce pill burden; ensure that all the key pharmacological therapies to lower cardiovascular risk after stroke are used; separate the decision to treat from the underlying level of the risk factor; and reduce monitoring burden (and costs). Evidence from trials in other populations, including people at high risk of cardiovascular disease and people with a history of myocardial infarction, suggests that such a regime is at least as effective as standard care. The purpose of this study is to determine whether an FDC pill has a role for secondary prevention of vascular events in older people who have had a stroke/TIA, in a primary care setting.

Who can participate?
Patients aged 55 years or over who have had a stroke or mini-stroke.

What does the study involve?
Following informed consent and initial health check, participants are randomly allocated into one of two groups. One group are given the polypill. The other group continue to receive standard care (separate antihypertensives and cholesterol lowering pills). Participants then have a follow-up health check at 6 months. After that, the study ends and participants on the polypill go back to standard care.

What are the possible benefits and risks of participating?
The risks of participating in this study are low. For participants treated with Trinomia, the risk of side effects are likely to be similar to those of the medicines they are taking already. Potential benefits for participants may include better management of risk factors for having another stroke. The results of the study may improve the future care of participants and other patients who have had a stroke.

Where is the study run from?
University of Cambridge (UK).

When is the study starting and how long is it expected to run for?
September 2015 to March 2018.

Who is funding the study?
British Heart Foundation (UK) and the Stroke Association (UK).

Who is the main contact?
Dr Merel Pannebakker
props@medschl.cam.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof Jonathan Mant

ORCID ID

http://orcid.org/0000-0002-9531-0268

Contact details

Primary Care Unit
Department of Public Health & Primary Care
Strangeways Research Laboratory
Worts Causeway
University of Cambridge
Cambridge
CB1 8RN
United Kingdom

Type

Public

Additional contact

Dr Merel Pannebakker

ORCID ID

Contact details

Primary Care Unit
Department of Public Health & Primary Care
Strangeways Research Laboratory
Worts Causeway
University of Cambridge
Cambridge
CB1 8RN
United Kingdom

Additional identifiers

EudraCT number

2013-004722-29

ClinicalTrials.gov number

Protocol/serial number

PROPS14

Study information

Scientific title

PROPS - Preventative Role of a fixed dose combination Pill in Stroke: a multi-centre open label randomised controlled trial of a fixed dose combination pill versus standard care for secondary prevention of stroke in a primary care setting

Acronym

PROPS

Study hypothesis

Current hypothesis as of 28/07/2015:
A fixed dose combination pill, Trinomia, will be non-inferior in terms of systolic blood pressure when compared with standard care in people with a history of stroke/TIA in a primary care setting over a period of 25 weeks.

Previous hypothesis:
A 'polypill' will be non-inferior in terms of systolic blood pressure when compared with standard care in people with a history of stroke/TIA in a primary care setting over a period of six months.

On 28/07/2015 the following changes were made to the trial record:
1. The public title was changed; the previous title was 'Preventative Role Of Polypill in Stroke (PROPS): Can a 'polypill' help reduce the chance that people who have had a stroke will have a heart attack or another stroke?'
2. The scientific title was changed; the previous title was 'Preventative Role Of Polypill in Stroke (PROPS): A multi-centre randomised controlled trial of a 'polypill' strategy versus standard care for secondary prevention of stroke in a primary care setting'
3. The overall trial start date was changed from 01/11/2014 to 01/09/2015.
4. The overall trial end date was changed from 01/11/2016 to 31/03/2018

Ethics approval

East Midlands – Nottingham 2 REC, 21/07/2015, ref: 15/EM/0277

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

GP practices

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Stroke prevention

Intervention

Current interventions as of 28/07/2015:
Participants in the intervention arm will receive Trinomia, a fixed dose combination pill, and participants in the control arm will receive standard ('normal') care, for a period of 6 months. Participants will be seen 2 weeks after starting the intervention, and again at 6 months for follow-up.

Previous interventions:
Participants in the intervention arm will receive a 'polypill' and participants in the control arm will receive standard ('normal') care for a period of 6 months. Participants will be seen 6 weeks after randomisation and again at 6 months for follow-up.

Intervention type

Drug

Phase

Phase III

Drug names

Trinomia (5mg Ramipril, 20mg atorvastatin, 100mg acetylsalicylic acid)

Primary outcome measures

Current primary outcome measures as of 28/07/2015:
Systolic blood pressure at baseline and follow-up at 25 weeks

Previous primary outcome measures:
To determine whether a 'polypill' will be non-inferior in terms of systolic blood pressure when compared with standard care in people with a history of stroke/TIA in a Primary Care setting over a period of six months

Secondary outcome measures

Current secondary outcome measures as of 28/07/2015:
1. Non-HDL, HDL & total cholesterol (baseline and follow-up at 25 weeks)
2. Diastolic BP (baseline and follow-up at 25 weeks)
3. Quality of life (EQ5D-5L; baseline and follow-up at 25 weeks)
4. Side effects (baseline and follow-up at 25 weeks)
5. Participant preference for a single pill (baseline, 2 weeks and follow-up at 25 weeks)
6. Subjective and objective measures of adherence (MARS, NINA, attitudes towards medication, BMQ; baseline, 2 weeks and follow-up at 25 weeks)
7. Lifestyle measures (diet, physical activity [GPPAQ], smoking and alcohol; baseline and follow-up at 25 weeks)
8. Stroke, TIA, myocardial infarction, cardiovascular events, cardiovascular deaths, all-cause mortality and any hospital admissions possibly associated with AEs of Trinomia (follow-up at 25 weeks)
9. Costs (follow-up at 25 weeks)

Previous secondary outcome measures:
To determine:
1. Whether taking the 'polypill' is associated with higher adherence and/or false reassurance in people with a history of stroke/TIA (pill count, single item adherence measure, MARS, NINA, BMQ).
2. The cost effectiveness of a 'polypill' strategy for secondary prevention of stroke as compared to standard practice (participant characteristics [age, gender, existing condition], type and dose of medication, adherence, resource use, EuroQol EQ-5D).
3. Non-inferiority of the 'polypill' for the following measurements: LDL cholesterol; HDL cholesterol; total cholesterol; triglycerides; change in diastolic blood pressure; quality of life (EuroQol EQ-5D); side effects; participant and carer preference for treatment; major cardiovascular events, strokes, myocardial infarction and all-cause mortality.

Overall trial start date

01/09/2015

Overall trial end date

31/03/2018

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 28/07/2015:
1. Men and post-menopausal* women, aged 55 years or over at the point of the database search
2. On the stroke/TIA register of the general practice.
*Post-menopausal defined as: no menstrual period for 12 consecutive months or more.

Previous inclusion criteria:
Participants eligible for the trial must comply with all of the following at randomisation:
1. Age 55 or over
2. On the stroke/TIA register of the general practice

Participant type

Patient

Age group

Senior

Gender

Both

Target number of participants

1222

Participant exclusion criteria

Current exclusion criteria as of 28/07/2015:
1. Confirmed diagnosis of haemorrhagic stroke
2. Currently receiving treatment with more than the equivalent of 20 mg of atorvastatin
3. Currently receiving treatment with clopidogrel anti-platelet monotherapy
4. Currently receiving treatment with anti-coagulant therapy
5. SBP <120mmHg
6. Orthostatic hypotension(≥20mmHg postural drop in SBP after 1 minute of standing)
7. Terminal illness
8. Known left ventricular systolic dysfunction (ejection fraction < 30%)
9. Absolute contra-indication to atorvastatin, aspirin or ramipril as specified in the SmPC or British National Formulary (BNF) or hypersensitivity to these components
10. Inability to give informed consent
11. Deemed unsuitable by General Practitioner (GP) for other reasons
12. Women of child bearing potential
13. Unable to swallow tablets or capsules
Involvement in any other trial is not an exclusion criterion.

Previous exclusion criteria:
1. On 3 or more antihypertensive agents
2. On more than the equivalent of 40mg simvastatin
3. Systolic blood pressure < 120mmHg
4. Orthostatic hypotension (≥20mmHg drop in systolic blood pressure on standing measured after 1 minute of standing)
5. Terminal illness
6. Heart failure
7. Absolute contra-indication to any of the components of the 'polypill'
8. Inability to give informed consent and without a designated representative who is able to provide consent under the terms of the Mental Capacity Act 2008
9. Deemed unsuitable by General Practitioner (GP) for other reasons

Recruitment start date

01/09/2015

Recruitment end date

31/03/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

100 GP practices in the UK
-
United Kingdom

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation Trust (UK)

Sponsor details

c/o Carrie Bayliss
Cambridge Clinical Trials Unit
Addenbrooke's Hospital
Level 6
Coton House
Box 401
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.cuh.org.uk/clinical-trials/cambridge-clinical-trials-unit-cctu

Funders

Funder type

Charity

Funder name

British Heart Foundation (UK)

Alternative name(s)

BHF

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United Kingdom

Funder name

Stroke Association (UK)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

professional associations and societies

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes