Condition category
Circulatory System
Date applied
04/08/2011
Date assigned
19/12/2011
Last edited
14/08/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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, Guy’s & 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?
Dr Martyn R Thomas
martyn.thomas@gstt.nhs.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Martyn Thomas

ORCID ID

Contact details

Cardiovascular Division
6th Floor
East Wing
St Thomas' Hospital
London
SE1 7EH
United Kingdom
+44 (0)20 7188 7188
martyn.thomas@gstt.nhs.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

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

Not provided at time of registration

Study design

Prospective randomised controlled study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial 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

Phase

Not Applicable

Drug names

Primary outcome measures

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 trial start date

01/10/2011

Overall trial end date

01/10/2015

Reason abandoned

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

Patient

Age group

Adult

Gender

Both

Target number of participants

310 patients randomised to 2 arms PLUS 2 registries

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

01/10/2011

Recruitment end date

01/10/2015

Locations

Countries of recruitment

France, Germany, United Kingdom

Trial 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
United Kingdom
+44 (0)20 7188 5736
karen.ignatian@gstt.nhs.uk

Sponsor type

Hospital/treatment centre

Website

http://www.guysandstthomas.nhs.uk/

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

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2014 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/25059340

Publication citations

  1. Protocol

    Khawaja MZ, Wang D, Pocock S, Redwood SR, Thomas MR, The percutaneous coronary intervention prior to transcatheter aortic valve implantation (ACTIVATION) trial: study protocol for a randomized controlled trial., Trials, 2014, 15, 300, doi: 10.1186/1745-6215-15-300.

Additional files

Editorial Notes