TIMES: Ticagrelor vs. Placebo/ Clopidogrel With Aspirin in Anterior STEMI Patients Treated With Primary PCI

May 25, 2017 updated by: Papworth Hospital NHS Foundation Trust

A Randomised Mechanistic Study Comparing the Effects of Different Anti-platelet Combinations (Ticagrelor vs. Placebo/ Clopidogrel) With Aspirin in Patients Presenting With Anterior STEMI Treated With Primary PCI

This is a single-centred, double blind randomized controlled trial comparing ticagrelor with placebo in clopidogrel and aspirin loaded patients.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The very early benefit of ticagrelor in STEMI is co-mediated by adenosine cardioprotection maintaining/ improving myocardial microcirculatory function, as well as via platelet inhibition or possibly other pleiotropic effects.

Ticagrelor increases circulating adenosine by reducing cellular re-uptake. Adenosine is a cardioprotective agent that utilizes cellular survival kinase pathways that may have beneficial effects on the microcirculation and myocardium in patients presenting with STEMI. Adenosine is currently used as a treatment for no-reflow and improves MVO post-STEMI when administered during PPCI. A recent study of healthy volunteers has confirmed that non-invasive coronary flow is augmented by ticagrelor and that this is mediated by adenosine. The Investigators propose that the very early beneficial effects of Ticagrelor in ACS may be adenosine mediated cardioprotection, rather than only due to an antiplatelet effect. This important research is original and a natural progression of the ticagrelor story. It expands the adenosine hypothesis and mode of action of ticagrelor and addresses a novel cardioprotective/ microcirculatory mechanism of action.

Study Type

Interventional

Enrollment (Anticipated)

140

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Cambridge
      • Papworth Everard, Cambridge, United Kingdom, CB23 3RE
        • Recruiting
        • Papworth Hospital NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Stephen Hoole

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Provision of informed verbal consent prior to any study specific procedures taking place with written consent confirmed prior to in-patient cardiac MRI.
  2. Male or female adult patient aged 18 - 90 years old
  3. Anterior STEMI (ST elevation ≥ 2mmHg in contiguous chest leads) with chest pain symptom onset < 12 hours

Exclusion Criteria:

  1. Cardiogenic shock*
  2. Previous anterior myocardial infarction
  3. Unfavourable coronary anatomy for PCI: left main / surgical or distal coronary disease
  4. Already prescribed Ticagrelor at the time of admission
  5. Factors affecting study drug administration/ absorption: vomiting or allergy
  6. Concomitant use of potent CYP3A4 inhibitors/ inducers (e.g ketoconazole and rifampicin) or CYP3A4 substrates with a narrow therapeutic window (e.g. cisapride and ergot alkaloids) or simvastatin / lovostatin >40mg oral dose.
  7. Severe bleeding diathesis or current active bleeding*
  8. History of intracranial haemorrhage
  9. Moderate or Severe hepatic impairment
  10. Severe asthma or bradycardia/ complete heart block (contraindications to adenosine)*
  11. Severe co-morbidity with a life expectancy < 3 months.

  12. Women of child bearing potential (as determined by direct questioning of the patient to confirm and this will be documented in the medical notes).

    • Patients that are found to have any excluding factor (e.g., unfavourable coronary anatomy for PCI) or develop any excluding factor (e.g., vomiting or cardiogenic shock) before the point of final IMR assessment will be discontinued from the study and followed up at discharge and by telephone at 3 and 12 months for adverse event monitoring purposes only.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ticagrelor
Patients will receive Ticagrelor 180mg (2 x 90mg tablets)
Drug: Ticagrelor
2 x 90mg Ticagrelor tablets
Placebo Comparator: Placebo
Patients will receive Placebo (2 matching tablets)
Other: Placebo
2 x matching placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Index of Myocardial Resistance (IMR)
Time Frame: Baseline to end of PPCI procedure.
To compare final Index of Myocardial Resistance (IMR) at the end of the PPCI procedure between the two arms.
Baseline to end of PPCI procedure.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Baseline IMR and change in IMR during PPCI
Time Frame: Baseline to end of PPCI procedure.
To compare between the two arms.
Baseline to end of PPCI procedure.
ACF and AMR pre/post PPCI
Time Frame: Baseline to end of PPCI procedure.
To compare between the two arms.
Baseline to end of PPCI procedure.
TIMI flow and TMBG pre/post PPCI
Time Frame: Baseline to end of PPCI procedure.
To compare between the two arms.
Baseline to end of PPCI procedure.
ST segment resolution
Time Frame: Baseline to end of PPCI procedure.
To compare between the two arms.
Baseline to end of PPCI procedure.
OCT quantified clot volume pre/post PPCI
Time Frame: Baseline to end of PPCI procedure.
To compare between the two arms.
Baseline to end of PPCI procedure.
Cardiac troponin - I and CKMB levels at 0, 12 and 24 hours
Time Frame: Baseline to 24 hours.
To compare between the two arms.
Baseline to 24 hours.
Cardiac MRI microvascular obstruction between 24-48 hours and infarct size at 3 months
Time Frame: Baseline to 3 months.
To compare between the two arms.
Baseline to 3 months.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Creatinine levels (eGRF) at 0, 12 and 24 hours
Time Frame: Baseline to 24 hours.
Safety endpoint.
Baseline to 24 hours.
NYHA Functional Classification and CCS Angina Grading Scale
Time Frame: Discharge to 12 months.
Clinical grading scales of heart failure and angina.
Discharge to 12 months.
Plasma Ticagrelor levels at the point of final IMR measurement and in-patient Cardiac MRI.
Time Frame: End of PPCI procedure to 24-48 hours.
This will explore if the IMR differences observed are related to individual differences in drug levels.
End of PPCI procedure to 24-48 hours.
Plasma Adenosine levels at the point of final IMR measurement and in-patient Cardiac MRI
Time Frame: End of PPCI procedure to 24-48 hours.
This will explore if the IMR differences observed are related to individual differences in adenosine levels.
End of PPCI procedure to 24-48 hours.
Multiplatelet® ADP aggregation assessment of platelet reactivity at the point of final IMR measurement and in-patient Cardiac MRI
Time Frame: End of PPCI procedure to 24-48 hours.
This will explore if the IMR differences observed are related to individual differences in platelet reactivity levels.
End of PPCI procedure to 24-48 hours.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Papworth Hospital NHS Foundation Trust

Collaborators

AstraZeneca

Investigators

  • Principal Investigator: Stephen Hoole, Papworth Hospital NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 30, 2017

Primary Completion (Anticipated)

November 30, 2018

Study Completion (Anticipated)

November 30, 2019

Study Registration Dates

First Submitted

April 13, 2017

First Submitted That Met QC Criteria

May 4, 2017

First Posted (Actual)

May 9, 2017

Study Record Updates

Last Update Posted (Actual)

May 30, 2017

Last Update Submitted That Met QC Criteria

May 25, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P01910

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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