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

NHS Foundation Trust

Status and phase: Unknown; Phase 2

Conditions: ST Elevation Myocardial Infarction

Treatments: Drug: Ticagrelor; Other: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03145194

P01910

Details and patient eligibility

About

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

Full 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.

Enrollment: 140 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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140 participants in 2 patient groups, including a placebo group

Ticagrelor

Experimental group

Description:

Patients will receive Ticagrelor 180mg (2 x 90mg tablets)

Treatment:

Drug: Ticagrelor

Placebo

Placebo Comparator group

Description:

Patients will receive Placebo (2 matching tablets)

Treatment:

Other: Placebo