Condition category
Circulatory System
Date applied
04/02/2014
Date assigned
23/06/2014
Last edited
07/04/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
A blocked or seriously narrowed coronary artery (that supply the heart) usually causes chest pain during exercise or a heart attack when blood supply to the heart muscle is interrupted. This is commonly treated using Percutaneous Coronary Intervention (PCI). During this treatment, a wire is inserted into the coronary artery, a small balloon is inflated to open up the blockage and a small tube called a coronary stent is left in place to help keep the coronary artery open. Although this is a very effective treatment, there is a risk of new blood clots forming after the PCI and causing another blockage in the coronary artery. For this reason, patients are routinely treated with drugs, such as Clopidogrel and Aspirin. These drugs work by reducing the activity of a type of blood cells, called platelets, which are part of the normal blood clotting process, but also cause abnormal clots in coronary arteries. For many patients who have a coronary stent inserted during a PCI treatment, a 6 to 12 month course of Clopidogrel and Aspirin are given in combination. Aspirin alone is given on its own following the Clopidogrel and Aspirin course. Recently, a new anti-platelet drug called Ticagrelor has been developed that is similar to Clopidogrel, but has a more powerful effect on blood platelets. Ticagrelor in combination with Aspirin is now given to some groups of NHS patients after PCI because a large clinical study has shown that this Ticagrelor with Aspirin is better at preventing abnormal blood clots than Clopidogrel used in combination with Aspirin. Ticagrelor is only routinely used at present in combination with Aspirin. However, Ticagrelor is a powerful anti-platelet drug that almost completely reduces the activity of platelets tested in the laboratory, even without additional Aspirin. This could mean that it is unnecessary to give patients Aspirin as well as Ticagrelor to prevent blood clot formation after coronary stent insertion. This may be beneficial to patients because Aspirin treatment can cause some side effects such as stomach bleeding. This study will identify whether patients who have had a coronary stent inserted also have fully reduced platelet activity during treatment with Ticagrelor. We will do this by measuring the activity of platelets in blood samples using sensitive laboratory tests. We will then compare the test results from participants taking Ticagrelor alone to test results from participants taking Ticagrelor in combination with Aspirin and other combinations of anti-platelet drugs.

Who can participate?
Patients who have had a PCI treatment at the Bristol Heart Institute (UK) with stent insertion for heart disease and have received a course of Clopidogrel and Aspirin will be eligible to participate.

What does the study involve?
Each participant will be asked to attend 3 study visits:
Study visit 1 will occur after a course of therapy with Aspirin and Clopidogrel (i.e: at the time dual antiplatelet therapy would be stopped in routine care and participants would have continued indefinitely with daily Aspirin alone). Eligible participants will give consent and give blood sample 1 for platelet testing. The patient will be randomly allocated to one of two different treatment groups. The Aspirin + Ticagrelor group will receive Ticagrelor (180 mg) followed by Ticagrelor 90 mg twice a day along with Aspirin once a day for 4 weeks. The Ticagrelor alone group will receive a starting dose of Ticagrelor (180 mg) followed by Ticagrelor 90mg twice a day, but no Aspirin for 4 weeks.
Study visit 2 will be 4 weeks after the study visit 1. All participants will give another blood sample for platelet testing. Medication for participants in both groups will then be changed to Aspirin 75 mg/day only.
Study visit 3 will be 4 weeks after the study visit 2. All participants will again give blood sample for platelet testing. Participants will then continue on Aspirin only, as usual care.

What are the possible benefits and risks of participating?
We will know about the effects of Ticagrelor on platelet function when used as a part of a dual anti-platelet treatment with Aspirin and as a single anti-platelet treatment. These results will enable direct comparison of how well these alternative Ticagrelor treatment regimens work and comparison with existing anti-platelet regimens (Aspirin alone and Aspirin+ Clopidogrel). There is no direct benefit to participants, other than the knowledge that they are helping to improve care for all future patients (which may include themselves, friends or family). Apart from the small risks associated with taking blood samples, there is also a risk of side effects to Ticagrelor, the most common being shortness of breath.

When is the study starting and how long is it expected to run for?
The study started in December 2015 and will be completed within 22 months.

Where is the study run from?
The study will be performed at University Hospitals Bristol (UHB), UK.

Who is funding the study?
The study is funded by AstraZeneca's UK Marketing Company (UKMC).

Who is the main contact?
Dr Andrew Mumford
a.mumford@bristol.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Andrew Mumford

ORCID ID

Contact details

University of Bristol
Bristol Heart Institute
Level 7 BRI
Bristol
BS2 8HW
United Kingdom

Additional identifiers

EudraCT number

2013-002734-20

ClinicalTrials.gov number

Protocol/serial number

v6.0 10/07/2015

Study information

Scientific title

A randomised controlled trial investigating the pharmacodynamic effect of TicagrElor Monotherapy on PLATElet reactivity in patients with coronary artery disease

Acronym

TEMPLATE

Study hypothesis

Platelets from patients taking ticagrelor alone and from patients taking aspirin and ticagrelor show similar levels of reactivity defined as the maximum amplitude of the light transmission aggregation response to Thrombin receptor agonist peptide-6 (TRAP)

Ethics approval

South Central - Oxford A, 23/10/2014, ref: 14/SC/1309

Study design

Single centre open-label randomised controlled trial

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
Ischaemic heart disease

Intervention

Study visit 1: All participants will give blood sample 1 for platelet testing, receive a loading dose of 180mg ticagrelor, and will be randomised to one of the interventional groups below.
1. Aspirin + ticagrelor (aspirin 75mg/day AND ticagrelor 90 mg b.d. (twice daily)) for 4 weeks, or
2. Ticagrelor (90 mg b.d) for 4 weeks.

Study visit 2: Participants will give blood sample 2 for platelet testing. Medication for participants in both groups will then be changed to aspirin 75 mg/day only.

Study visit 3: All participants will give blood sample 3 for platelet testing. Participants will then continue on aspirin only, as per standard care (usually under the supervision of their GP).

Intervention type

Drug

Phase

Not Applicable

Drug names

Ticagrelor

Primary outcome measures

Maximum amplitude of the light transmission aggregation response of platelet rich plasma (PRP) to 10 µM TRAP expressed as a % of the absolute difference in light transmission between PRP and platelet poor plasma. This assay measures the ability of platelets to aggregate when exposed to the aggregation promoting agent TRAP.

Measured at each visit, i.e. at visit 1 (baseline visit), at visit 2 (4 weeks after the baseline visit), and at visit 3 (8 weeks after the baseline visit).

Secondary outcome measures

1. Light transmission aggregation responses to collagen and to ADP, arachidonic acid and the thromboxane (TP) receptor agonist U46619. This assay measures the ability of platelets to aggregate when exposed to the aggregation promoting agents collagen, ADP, arachidonic acid and U46619.
2. Flow cytometry to quantify surface CD62P expression and PAC-1 binding before and after activation with collagen and TRAP6. This assay measures the exposure of surface activation markers.
3. Plasma concentrations of soluble CD40 ligand (sCD40L) and thromboxane B2 to assess baseline in vivo platelet activation and Thromboxane A2 (TxA2) bio-synthesis respectively. This assay measures the levels of chemicals in the blood that are released when a platelet is activated and reflects the extent of platelet activation in the circulation.

Measured at each visit, i.e. at visit 1 (baseline visit), at visit 2 (4 weeks after the baseline visit), and at visit 3 (8 weeks after the baseline visit).

Overall trial start date

14/12/2016

Overall trial end date

14/12/2018

Reason abandoned

Eligibility

Participant inclusion criteria

Participant may enter study if ALL of the following apply
1. Patient is treated with dual antiplatelet therapy comprising aspirin and clopidogrel for a minimum of 4 weeks (amended from: for 12 months as of 31/03/2016)
2. The patient is scheduled to stop dual antiplatelet therapy and continue with aspirin monotherapy

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

110

Participant exclusion criteria

Participant may not enter study if ANY of the following apply
1. Contraindication to dual antiplatelet therapy
2. Interruption of dual antiplatelet therapy because of bleeding events or increased bleeding risk
3. Contraindications to the use of ticagrelor
4. Pregnant and or lactating women
5. Women with child bearing potential (i.e. not sterilised or not post-menopausal) who are unwilling to use contraception
6. Men with a spouse or partner with child bearing potential unless the participant has agreed to use condoms

Recruitment start date

15/01/2016

Recruitment end date

15/10/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Bristol
Bristol
BS2 8HW
United Kingdom

Sponsor information

Organisation

University Hospitals Bristol NHS Foundation Trust

Sponsor details

c/o Mrs Diana Benton
Research and Innoveation Department
UHBristol Education Centre
Level 3 Upper Maudlin Street
Bristol
BS2 8AE
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Industry

Funder name

AstraZeneca

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United Kingdom

Results and Publications

Publication and dissemination plan

1. Protocol paper: 2016
2. Results paper: 2018

Intention to publish date

31/12/2016

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

07/04/2016: Ethics approval information added. 31/03/2016: Ethics approval date added. Overall start date changed from 15/03/2014 to 14/12/2016. Over end date changed from 15/02/2016 to 14/12/2018. Recruitment start date changed from 15/03/2014 to 15/01/2016. Recruitment end date changed from 15/02/2016 to 15/10/2017.