Plain English Summary
Background and study aims
A novel treatment called transcatheter aortic valve implantation (TAVI) now allows patients who are too high risk to undergo open-heart surgery to have their very stiff heart valves (the aortic valve) replaced. This is achieved using a valve replacement put in place using a balloon, introduced through only a small cut into an artery or the heart itself. The process which leads to this stiffening of the valve is related to that which leads to narrowing within the heart's coronary arteries. In patients undergoing open-heart surgery to replace the valve, any such narrowings can be treated at the same time using a technique called bypass grafting or a 'heart bypass'. This has been shown to be better than not treating these arteries. However, we do not know the best treatment for these narrowed arteries in patients undergoing TAVI. In these patients the alternative to heart bypass surgery is to use a balloon and stent(s) to widen the artery and relieve the narrowing (percutaneous coronary intervention or PCI). This is achieved using very thin tubes passed to the heart either via an artery in the groin or the wrist. However, this has its own risks and it may be better for the patient to not have these narrowings opened until they present the main problem.
Who can participate?
Patients must be 18 years of age or over with severe aortic stenosis.
What does the study involve?
We will randomly assign 310 patients with significant narrowing in their coronary arteries to either undergo PCI or to not undergo PCI. We will then follow these patients up, as well as patients without significant narrowings and those who cannot have the PCI procedure performed. The aim is to answer the question of whether patients with significant narrowings of their coronary arteries who are due to undergo a TAVI for a severely stiffened aortic heart valve should have stenting first, or not. The study compares the effects of treating or not treating coronary artery disease using stenting prior to TAVI.
What are the possible benefits and risks of participating?
There is no direct benefit to study participants, clinical or otherwise. The information we will get will help improve the treatment of other people with similar conditions in the future. We do not know if the stenting has any beneficial or negative effects upon patients undergoing TAVI. The possible risks of undergoing the stenting procedure are similar to that of your coronary angiogram: blockage of the stent by a process known as thrombosis and excess healing of the artery wall causing restenosis of the stent. Other major complications are uncommon, but include: death, heart attack, which may require emergency heart bypass, stroke and bleeding. Minor complications are: allergy to the contrast medium, impairment of kidney function and complications at the access site, such as bleeding and haematoma. The risks of stenting are much lower than the risks associated with the TAVI procedure.
Where is the study run from?
The lead centre for the trial is the Cardiovascular Department, Guys & St Thomas NHS Foundation Trust, London, UK. The total number of centres involved is to be confirmed. It will involve centres across the UK and the EU.
When is the study starting and how long is it expected to run for?
We expect to begin recruitment of patients in late 2011 and will follow up the patients for 12 months. The expected duration of the trial is 3 years.
Who is funding the study?
The trial is funded by educational grants provided by Boston Scientific Inc. (MA, USA) and Edwards LifeSciences (CA, USA).
Who is the main contact?
Prof Simon Redwood
simon.redwood@gstt.nhs.uk
(updated 24/11/2020, previously: Dr Martyn R Thomas
martyn.thomas@gstt.nhs.uk)
Study website
Contact information
Type
Scientific
Contact name
Prof Simon Redwood
ORCID ID
Contact details
Cardiovascular Division
6th Floor
East Wing
St Thomas' Hospital
London
SE1 7EH
United Kingdom
+44 (0)20 7188 7188
simon.redwood@gstt.nhs.uk
Additional identifiers
EudraCT/CTIS number
IRAS number
ClinicalTrials.gov number
Secondary identifying numbers
ACTIVATION v2.7
Study information
Scientific title
PercutAneous Coronary inTerventIon prior to transcatheter aortic VAlve implantaTION: a randomised controlled trial (ACTIVATION)
Acronym
ACTIVATION
Study hypothesis
Re-vascularisation of significant coronary artery disease by percutaneous coronary intervention (PCI) prior to transcatheter aortic valve implantation (TAVI) reduces the rate of mortality (and re-hospitalisation) at thirty days and twelve months after the valvular intervention compared to no such revascularisation.
Ethics approval(s)
Not provided at time of registration
Study design
Prospective randomised controlled study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Coronary artery disease & aortic stenosis
Intervention
1:1 Randomisation of pre-TAVI PCI to no pre-TAVI PCI. The 310 patients will be enrolled from 20 - 30 UK and European centres plus 2 registries.
1. Coronary angiography will be used to identify significant coronary artery disease (CAD) defined as ≥1 lesion of ≥70% in ≥1 epicardial coronary artery
2. Patients without significant CAD will be enrolled into Registry 1
3. Patients whose CAD is not suitable for percutaneous coronary intervention (PCI) will be enrolled into Registry 2
4. The remaining patients with CAD amenable to PCI will be randomised into 2 arms with a 1:1 ratio:
4.1. To receive PCI
4.2. To not undergo PCI
Intervention type
Other
Primary outcome measure
A comparison of mortality and re-hospitalisation at 12 months
Secondary outcome measures
1. Mortality at 12 months
2. Major adverse cardiovascular and cerebrovascular events (MACCE) at 30 days and 12 months
3. Hospitalisation for heart failure at 30 days and 12 months
4. Procedural complications
5. Procedural success
6. Bleeding Complications
7. Access site complications
8. Transient ischaemic attacks
9. Duration of hospital stay
10. Anginal burden
Overall study start date
01/10/2011
Overall study end date
11/02/2020
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients ≥18 years of age
2. Severe aortic stenosis, as defined by:
2.1. Peak transvalvular gradient of ≥40mmHg on transthoracic echocardiography (TTE)
2.2. Transoesophageal echocardiography (TOE)
2.3. Dobutamine stress echocardiography (DSE)
3. Aortic valve area of <1.0cm2
4. Symptoms suggestive of aortic stenosis (dyspnoea, syncope etc)
5. Deemed prohibitive risk for open aortic valve replacement (AVR) by a multi-disciplinary TAVI multidisciplinary team (MDT), as previously defined, and accepted for TAVI by said TAVI MDT
6. ≥1 proximal stenosis of ≥70% in a major epicardial artery deemed suitable for percutaneous coronary intervention (PCI) TAVI via any accepted approach (transfemoral, transapical, subclavian or transaortic) using any CE marked device
7. Written informed consent
Participant type(s)
Patient
Age group
Adult
Lower age limit
18 Years
Sex
Both
Target number of participants
310 patients randomised to 2 arms PLUS 2 registries
Total final enrolment
235
Participant exclusion criteria
1. An obvious acute coronary syndrome within 30 days of randomisation
2. Left main stem disease
3. Pregnancy
4. Active internal bleeding (except menstruation)
5. Allergy to heparin or glycoprotein (GP) IIb/IIIa inhibitors
6. Thrombocytopoenia (platelet count < 100,000 cells/mm3)
7. Patients who have previously been enrolled in this study
8. Patients who are currently enrolled in any other study where involvement in ACTIVATION would involve deviation from either protocol
Recruitment start date
04/12/2012
Recruitment end date
11/01/2019
Locations
Countries of recruitment
England, France, Germany, United Kingdom
Study participating centre
Cardiovascular Division
London
SE1 7EH
United Kingdom
Sponsor information
Organisation
Guy's & St Thomas' NHS Foundation Trust (UK)
Sponsor details
c/o Ms Karen Ignatian
Research and Development
16th Floor
Guy's Hospital
Great Maze Pond
London
SE1 9RT
England
United Kingdom
+44 (0)20 7188 5736
karen.ignatian@gstt.nhs.uk
Sponsor type
Hospital/treatment centre
Website
http://www.guysandstthomas.nhs.uk/
ROR
Funders
Funder type
Industry
Funder name
Boston Scientific Inc. (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Edwards LifeSciences Inc. (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
31/01/2021
Individual participant data (IPD) Intention to share
No
IPD sharing plan
Not provided at time of registration
IPD sharing plan summary
Not provided at time of registration
Study outputs
Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
---|---|---|---|---|---|
Protocol article | protocol | 24/07/2014 | Yes | No | |
Results article | 27/09/2021 | 14/04/2022 | Yes | No |