The role of cerebral embolic protection in preventing strokes and improving other health outcomes in patients receiving a replacement heart valve
| ISRCTN | ISRCTN16665769 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16665769 |
| IRAS number | 276396 |
| Secondary identifying numbers | PID14772-SP001-AC001, IRAS 276396 |
- Submission date
- 26/02/2020
- Registration date
- 23/06/2020
- Last edited
- 16/04/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Circulatory System
Plain English Summary
Background and study aims
Transcatheter Aortic Valve Implementation (TAVI) is a standard treatment for Aortic Stenosis (AS), a condition where blood flow out of the heart is restricted by narrowing of the aortic valve. In a TAVI procedure, the aortic valve is replaced by placing a new valve delivered to the heart through a tube (catheter) placed in an artery. One risk associated with TAVI is stroke. During the TAVI procedure, debris (made up of parts of the diseased aortic valve and the surrounding tissue) can be released into the bloodstream. Most strokes occurring at the time of TAVI are due to this debris blocking part of the blood supply in the brain. Devices have been developed that capture some of the debris released and stop this reaching the brain, these are called Cerebral Embolic Protection (CEP) devices.
The purpose of this study is to assess whether using a Cerebral Embolic Protection (CEP) device during Transcatheter Aortic Valve Replacement (TAVI) can reduce the chance of a patient having a stroke. The study will also determine whether it improves the quality of life for patients and how the use of CEP impacts the NHS in terms of cost and service use.
Who can participate?
Patients aged 18 years or above, with aortic stenosis planned for treatment by TAVI.
What does the study involve?
In this study, patients who agree to take part (this means given written consent) receiving TAVI will be randomly assigned to receive CEP during TAVI or to the current standard of care without CEP. Potential participants will be approached prior to their TAVI procedure to discuss the trial.
What are the possible benefits and risks of participating?
We have no evidence that there are significant risks associated with using the CEP device. There are small risks associated with putting a device within an artery. These risks are less than 1% and include bleeding, infection or damage to the artery. The additional risks from the device are small.
The risks of a TAVI procedure itself include a 2-3% risk of stroke or death and a 10% risk of bleeding. You will be attended to and cared for by the standard care and clinical team throughout the procedure and your recovery.
If you take part in this study you will have a heart valve replacement procedure as part of your routine care. For some participants the procedure will be extended by about 10 minutes to place a cerebral embolic protection device. This time and procedure are extra to what you would have if you did not take part.
There is a small chance that patients in the TAVI with CEP arm will have to receive an small additional dose of X-ray contrast associated with the use of the CEP device. This could cause an injury to the kidney, however there are no reported cases of this happening to date.
The operation you are having uses ionising radiation to form images of your body. Ionising radiation can cause cell damage that may, after many years or decades, turn cancerous. Dose levels are monitored carefully during your intervention.
We are all at risk of developing cancer during our lifetime. The normal risk is that this will happen to about 50% of people at some point in their life. Having this procedure might increase the chances of this happening to you from 50% to 50.13%. If you are in the group receiving CEP, the time for this radiation would be extended by 10 minutes.
Where is the study run from?
This study is run by University of Oxford (UK) in collaboration with the London School of Hygiene and Tropical Medicine (UK)
When is the study starting and how long is it expected to run for?
April 2020 to October 2025
Who is funding the study?
1. British Heart Foundation (UK)
2. Boston Scientific Corporation (USA)
Who is the main contact?
Zahra Jamal, bhfprotect-tavi@LSHTM.ac.uk
Contact information
Public
Department of Medical Statistics
London School of Hygiene and Tropical Medicine
London
WC1E 7HT
United Kingdom
| Phone | +44 (0)20 7927 2723 |
|---|---|
| bhfprotect-tavi@lshtm.ac.uk |
Study information
| Study design | Prospective multicentre randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | ISRCTN16665769_PIS_v1.0_16Mar2020.pdf |
| Scientific title | British Heart Foundation Randomised Trial of Routine Cerebral Embolic Protection in Transcatheter Aortic Valve Implantation |
| Study acronym | BHF PROTECT-TAVI |
| Study hypothesis | Does the routine use of the Sentinel Cerebral Embolic Protection device during TAVI reduce stroke incidence? |
| Ethics approval(s) |
Approved 23/04/2020, Wales Research Ethics Committee 5 (Health and Care Research Wales Support and Delivery Centre, Castlebridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, United Kingdom; +44 (0)7970 422139; wales.rec5@wales.nhs.uk), ref: 20/WA/0121 |
| Condition | Aortic stenosis |
| Intervention | Current interventions as of 04/10/2024: The study is an RCT evaluating use of the cerebral embolic protection device (Sentinel, Boston Scientific) in participants with aortic valve stenosis planned for treatment by Transcatheter Aortic Valve Implantation (TAVI). Participants will be randomised 1:1 into a treatment cohort using the cerebral embolic protection device (Sentinel, Boston Scientific) or a control cohort with no cerebral protection system. Enrolled participants will be followed through 72 hours (or hospital discharge), whichever comes first, and assessed for the primary outcome. Consented patients will be randomised at a 1:1 ratio to either the control or intervention arm before their TAVI procedure. This will be done using a secure online randomisation service. The intervention group will have TAVI performed with CEP. The Claret Sentinel dual-filter device (Boston Scientific, MA, USA) is a single use, embolic protection catheter inserted into the right radial or brachial artery. This is the only device currently approved for clinical use in both Europe and the USA. The device employs two filters (nitinol frames with 140-micron pores polyurethane film), one delivered to the brachiocephalic artery (Proximal Filter), and one to the left common carotid artery (Distal Filter) before TAVI. Following the TAVI procedure the system is removed. _____ Previous interventions: The study is an RCT evaluating use of the cerebral embolic protection device (Sentinel, Boston Scientific) in participants with aortic valve stenosis planned for treatment by Transcatheter Aortic Valve Implantation (TAVI). Participants will be randomised 1:1 into a treatment cohort using the cerebral embolic protection device (Sentinel, Boston Scientific) or a control cohort with no cerebral protection system. Enrolled participants will be followed through 72 hours (or hospital discharge), whichever comes first, and assessed for the primary outcome. Consented patients will be randomised at a 1:1 ratio to either the control or intervention arm at the time of the their TAVI procedure. This will be done using a secure online randomisation service. The intervention group will have TAVI performed with CEP. The Claret Sentinel dual-filter device (Boston Scientific, MA, USA) is a single use, embolic protection catheter inserted into the right radial or brachial artery. This is the only device currently approved for clinical use in both Europe and the USA. The device employs two filters (nitinol frames with 140-micron pores polyurethane film), one delivered to the brachiocephalic artery (Proximal Filter), and one to the left common carotid artery (Distal Filter) before TAVI. Following the TAVI procedure the system is removed. |
| Intervention type | Device |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Cerebral embolic protection device (Sentinel, Boston Scientific) |
| Primary outcome measure | Current primary outcome measure as of 20/02/2025: The incidence of stroke at 72 hours post-TAVI, or hospital discharge (if sooner). Events will be validated by an independent clinical events committee blinded to trial treatment. _____ Previous primary outcome measure as of 04/11/2021: The incidence of stroke at 72 hours post-TAVI, or hospital discharge (if sooner). Events will be assessed by the local stroke team and validated by an independent clinical events committee blinded to trial treatment. _____ Previous primary outcome measure: The incidence of all stroke within 72 hours (or hospital discharge) of the TAVI procedure, measured using patient records |
| Secondary outcome measures | Current secondary outcome measures as of 04/10/2024: 1.Combined incidence of all-cause mortality or non-fatal stroke at 72 hours post-TAVI or hospital discharge (if sooner) 2. Combined incidence of all-cause mortality, non-fatal stroke or transient ischaemic attack at 72 hours post-TAVI or hospital discharge (if sooner). 3. Incidence of all-cause mortality at 72 hours post-TAVI or hospital discharge (if sooner) 4. Win ratio for all-cause mortality, disabling stroke and non-disabling stroke at 72 hours post-TAVI, or hospital discharge (if sooner) 5.Incidence of all-cause mortality at 12 months post-TAVI. 6. Incidence of all-cause mortality up to the end of the trial. This will use trial data up to 12 months, and centrally held NHS data from 12 months to the end of the trial 7. Incidence of stroke as defined by centrally held NHS data between 72 hours post-TAVI or hospital discharge (if sooner) and 30-days post-TAVI. 8. Incidence of stroke as defined by centrally held NHS data between 30-days post-TAVI and the end of the trial. 9. Stroke Severity: Assessed using the National Institutes of Health Stroke Scale (NIHSS) in participants who have had a stroke within 72-hours post-TAVI or hospital discharge (if sooner) 10. Disability Outcome Assessed using the Simple Modified Rankin Scale questionnaire (smRSq) up to 12 months post-TAVI in participants who have had a stroke within 72-hours post-TAVI or hospital discharge (if sooner) 11. Cognitive Outcome Assessed using the standardised Montreal Cognitive Assessment (MoCA) up to 12-months post-TAVI. 12. Vascular access site related complications (VARC-2 criteria) at 72-hours post-TAVI or hospital discharge (if sooner) and between 6-8 weeks post-TAVI 13. Cost-effectiveness analysis at 12 months _____ Previous secondary outcome measures as of 05/01/2024: 1. Combined incidence of all-cause mortality or non-fatal stroke at 72 hours post-TAVI, or hospital discharge (if sooner) 2. Combined incidence of all-cause mortality, non-fatal stroke and transient ischaemic attack at 72 hours post-TAVI or hospital discharge (if sooner) 3. Incidence of all-cause mortality at 72 hours and 12 months post-TAVI 4. Incidence of stroke as defined by centrally held NHS data between 72 hours post-TAVI (or discharge from hospital, if sooner) and 30-days post-TAVI 5. Incidence of stroke as defined by centrally held NHS data between 30-days post-TAVI and the end of the study 6. Stroke severity assessment in participants who have had a stroke within 72-hours post-TAVI or hospital discharge (if sooner) measured using NIHSS 7. Cognitive outcomes measured using the Montreal Cognitive Assessment up to 12 months post-TAVI 8. Disability outcomes in participants who have had a stroke up to 72 hours post-TAVI or discharge if sooner measured using simple modified Rankin Scale questionnaire up to 12 months post-TAVI 9. Vascular access site and access related complications according to standard criteria defined by the Valve Academic Research Consortium (VARC-2) at 72-hours post-TAVI or hospital discharge (if sooner) and between 6-8 weeks post-TAVI 10. Cost-effectiveness analysis using the EQ-5D-5L and data on resource utilisation at 12 months post-TAVI _____ Previous secondary outcome measures as of 29/11/2022: 1. Combined incidence of all-cause mortality or non-fatal stroke at 72 hours post-TAVI, or hospital discharge (if sooner) 2. Incidence of all-cause mortality at 72 hours and 12 months post-TAVI 3. Incidence of stroke as defined by centrally held NHS data between 72 hours post-TAVI (or discharge from hospital, if sooner) and 30-days post-TAVI 4. Incidence of stroke as defined by centrally held NHS data between 30-days post-TAVI and the end of the study 5. Stroke severity assessment in participants who have had a stroke within 72-hours post-TAVI or hospital discharge (if sooner) measured using NIHSS 5. Cognitive outcomes measured using the Montreal Cognitive Assessment up to 12 months post-TAVI 6. Disability outcomes in participants who have had a stroke up to 72 hours post-TAVI or discharge if sooner measured using simple modified Rankin Scale questionnaire up to 12 months post-TAVI 7. Vascular access site and access related complications according to standard criteria defined by the Valve Academic Research Consortium (VARC-2) at 72-hours post-TAVI or hospital discharge (if sooner) and between 6-8 weeks post-TAVI 8. Cost-effectiveness analysis using the EQ-5D-5L and data on resource utilisation at 12 months post-TAVI _____ Previous secondary outcome measures as of 04/11/2021: 1. Combined incidence of all-cause mortality or non-fatal stroke at 72 hours post-TAVI, or hospital discharge (if sooner) 2. Incidence of all-cause mortality at 72 hours and 12 months post-TAVI 3. Incidence of stroke as defined by centrally held NHS data between 72 hours post-TAVI (or discharge from hospital, if sooner) and 30-days post-TAVI 4. Incidence of stroke as defined by centrally held NHS data between 30-days post-TAVI and the end of the study 5. Cognitive/disability outcomes measured using the Montreal Cognitive Assessment and simple modified Rankin Scale questionnaire at 72-hours post-TAVI or at hospital discharge (if sooner), and up to 12 months post-TAVI 6. Vascular access site and access related complications according to standard criteria defined by the Valve Academic Research Consortium (VARC-2) at 72-hours post-TAVI or hospital discharge (if sooner) and between 6-8 weeks post-TAVI 7. Cost-effectiveness analysis using the EQ-5D-5L and data on resource utilisation at 12 months post-TAVI _____ Previous secondary outcome measures: Measured using patient records: 1. Combined incidence of all-cause mortality and stroke up to 12 months 2. Incidence of all-cause mortality up to 12 months 3. Cognitive outcomes up to 12 months 4. Vascular access site injury between 6-8 weeks post-TAVI 5. Acute kidney injury between 6-8 weeks post-TAVI 6. Cost-effectiveness analysis |
| Overall study start date | 01/04/2020 |
| Overall study end date | 09/10/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 9,712 |
| Total final enrolment | 7635 |
| Participant inclusion criteria | Current inclusion criteria as of 04/11/2021: 1. Participant is willing and able to give informed consent for participation in the trial 2. Aged 18 years or above 3. Considered to be candidates for TAVI by the clinical team (via any access route where CEP may be used) 4. Participant is suitable for treatment with the cerebral embolic protection device in the opinion of the treating physician Previous inclusion criteria: 1. Willing and able to give informed consent for participation in the trial. 2. Aged 18 years or above 3. Diagnosed with aortic stenosis (including bioprosthetic valve dysfunction) 4. Planned transfemoral TAVI |
| Participant exclusion criteria | Current exclusion criteria as of 04/11/2021: No specific exclusion criteria. Participants involved in observational studies will be eligible for this study. As this is an all-comer design, current or previous participation in other ongoing randomised trials will not be disqualifying for recruitment to this study unless treatment is expected to impact the effect of using a CEP device on stroke. _____ Previous exclusion criteria: 1. Anatomically unsuitable for treatment with the cerebral embolic protection device in the opinion of the treating physician 2. Clinical contra-indications to the use of the CEP device in the opinion of the treating physician |
| Recruitment start date | 29/10/2020 |
| Recruitment end date | 09/10/2024 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
Leeds
LS1 3EX
United Kingdom
Brighton
BN2 5BE
United Kingdom
Heath Town
Wolverhampton
WV10 0QP
United Kingdom
Cardiff
CF14 4XW
United Kingdom
Cwmrhydyceirw
Swansea
SA6 6NL
United Kingdom
Old Dalkeith Road
Edinburgh
Lothian
EH16 4SA
United Kingdom
London
EC1A 7BE
United Kingdom
De Crespigny Park
Denmark Hill
London
SE5 8AB
United Kingdom
Belfast
BT12 6BA
United Kingdom
Westminster Bridge Road
London
SE1 7EH
United Kingdom
Nethermayne
Basildon
SS16 5NL
United Kingdom
Thomas Drive
Liverpool
L14 3PE
United Kingdom
Crownhill
Plymouth
PL6 8DH
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
Clydebank
G81 4DY
United Kingdom
Cambridge Biomedical Campus
Cambridge
CB2 0AY
United Kingdom
London
SW17 0QT
United Kingdom
Blackpool
FY3 8NR
United Kingdom
Bristol
BS1 2LX
United Kingdom
Nottingham
NG5 1PB
United Kingdom
Du Cane Road
London
W12 0HS
United Kingdom
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Wythenshawe
Manchester
M23 9LT
United Kingdom
Cottingham
HU16 5JX
United Kingdom
Middlesbrough
TS4 3BW
United Kingdom
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
United Kingdom
Herries Road
Sheffield
S5 7AU
United Kingdom
Aberdeen
AB25 2ZN
United Kingdom
Stoke-on-trent
ST4 6QG
United Kingdom
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom
London
SW1X 7HY
United Kingdom
Sponsor information
University/education
Clinical Trials and Research Governance
Joint Research Office
1st floor, Boundary Brook House
Churchill Drive
Headington
Oxford
OX3 7GB
England
United Kingdom
| Phone | +44 (0)1865 616480 |
|---|---|
| ctrg@admin.ox.ac.uk | |
| Website | http://www.ox.ac.uk/ |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- the_bhf, The British Heart Foundation, BHF
- Location
- United Kingdom
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Boston Scientific, Boston Scientific Corp., BSC
- Location
- United States of America
Results and Publications
| Intention to publish date | 31/07/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in major international scientific journals and present them at academic conferences. Lay results for patients will be available upon request through our trial website and via their local hospital. |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version v1.0 | 16/03/2020 | 23/06/2020 | No | Yes |
| Protocol file | version 4.0 | 17/10/2022 | 29/11/2022 | No | No |
| Participant information sheet | version 7 | 29/07/2024 | 04/10/2024 | No | Yes |
| Protocol file | version 6 | 29/07/2024 | 04/10/2024 | No | No |
| Other files | Communication from the BHF PROTECT-TAVI Trial Steering Committee | 25/10/2024 | 28/10/2024 | No | No |
| Protocol (other) | 16/04/2025 | Yes | No | ||
| Results article | 30/03/2025 | 16/04/2025 | Yes | No | |
| Statistical Analysis Plan | 16/04/2025 | Yes | No |
Additional files
- ISRCTN16665769_PIS_v1.0_16Mar2020.pdf
- Uploaded 23/06/2020
- 37967 BHF PROTECT-TAVI_Protocol_v4.0_17Oct2022.pdf
- ISRCTN16665769 BHF PROTECT-TAVI_PIS_v7_29 07 24 Clean.pdf
- ISRCTN16665769 BHF PROTECT-TAVI_Protocol_v6_29 07 24 Clean.pdf
- ISRCTN16665769 BHF PROTECT-TAVI TSC communication 25.10.24 .pdf
- Communication from the BHF PROTECT-TAVI Trial Steering Committee
Editorial Notes
16/04/2025: Publication reference, protocol and statistical analysis plan added.
20/02/2025: The primary outcome measures were updated. The total final enrolment was changed from 7627 to 7635.
28/10/2024: Recruitment to the BHF PROTECT-TAVI trial was stopped on 9 October 2024. A communication from the BHF PROTECT-TAVI Trial Steering Committee is attached to the record in the outputs table.
14/10/2024: The following changes were made to the trial record:
1. The contact was changed.
2. The overall end date was changed from 28/02/2027 to 09/10/2025.
3. The phase was changed from IV to III.
4. The total final enrolment was added.
5. The recruitment end date was changed from 28/02/2026 to 09/10/2024.
6. The intention to publish date was changed from 31/08/2025 to 31/07/2026.
04/10/2024: The following changes were made to the trial record:
1. Uploaded protocol v6.0 (not peer-reviewed) as an additional file.
2. The participant information sheet v7 was uploaded as an additional file.
3. The overall end date was changed from 30/04/2026 to 28/02/2027.
4. The interventions were changed.
5. The secondary outcome measures were changed.
6. The target number of participants was changed from 7,730 to 9,712.
7. The recruitment end date was changed from 30/04/2025 to 28/02/2026.
8. The intention to publish date was changed from 31/07/2026 to 31/08/2025.
9. The study participating centre Cleveland Clinic was added.
05/01/2024: The following changes were made:
1. Ethics approval reference as added.
2. Walsgrave General Hospital was added as a study participating centre.
3. The secondary outcome measures were changed.
29/11/2022: The following changes were made to the trial record:
1. Uploaded protocol (not peer-reviewed) as an additional file.
2. The secondary outcome measures were changed.
3. The trial participating centres Leeds General Infirmary, Royal Sussex County Hospital, New Cross Hospital Royal Wolverhampton, University Hospital of Wales, Morriston Hospital, Royal Infirmary of Edinburgh, St. Bartholomews Hospital, King's College Hospital, The Royal Victoria Hospital, Guy's and St Thomas' NHS Foundation Trust, Basildon Hospital, Liverpool Heart & Chest Hospital, Derriford Hospital, Southampton General Hospital, Golden Jubilee National Hospital, Royal Papworth Hospital, St Georges Hospital, Blackpool Victoria Hospital, Bristol Heart Institute, Nottingham City Hospital, Hammersmith Hospital, Freeman Hospital, Wythenshawe Hospital, Castle Hill Hospital, James Cook University Hospital, Queen Elizabeth Hospital, Northern General Hospital, Aberdeen Royal Infirmary, Royal Stoke University Hospital were added.
17/11/2021: The plain English summary was updated to match the previous changes.
04/11/2021: The following changes were made to the trial record:
1. The overall trial start date was changed from 01/05/2020 to 01/04/2020.
2. The recruitment end date was changed from 31/01/2025 to 30/04/2025.
3. The intention to publish date was changed from 30/04/2026 to 31/07/2026.
4. The primary and secondary outcome measures and inclusion and exclusion criteria were updated.
16/03/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/03/2021 to 29/10/2020.
2. The contact email was updated.
3. A link to the participant information sheet was added to the participant information sheet field.
29/05/2020: Trial’s existence confirmed by NHS HRA.
