A 30 Day Study to Evaluate Efficacy and Safety of Pre-hospital vs. In-hospital Initiation of Ticagrelor Therapy in STEMI Patients Planned for Percutaneous Coronary Intervention (PCI)

Phase 4

Completed

Conditions: Myocardial Infarction
Segment Elevation Myocardial Infarction (STEMI)

Brief Summary: The aim of this study is to determine whether initiation of ticagrelor as early as in the ambulance setting leads to a rapid reperfusion of the infarct-related artery therefore facilitating the Percutaneous Coronary Intervention (PCI) and optimizing the outcome for the patient.

The study will assess the efficacy and safety of pre-hospital compared to in-hospital administration of ticagrelor in co-administration with aspirin, on restoring the blood flow in the occluded heart artery and improving the myocardial perfusion in patients suffering from myocardial infarction and planned to have a PCI. Patients can be randomised in either one of the 2 arms:

re-hospital ticagrelor arm: Patients will receive a loading dose of 180 mg ticagrelor for the pre-hospital administration and placebo for in-hospital administration.

or In-hospital ticagrelor arm: Patients will receive a placebo for pre-hospital administration and 180 mg ticagrelor loading dose for in-hospital administration.

Patients are initially managed by ambulance physician/personnel in pre hospital settings. They are then transferred into a Catheterization room to undergo a PCI.

After the administration of the loading dose of ticagrelor (double blind), patients will continue on ticagrelor 90 mg bid and be followed in study for 30 days post randomisation.

Recruitment & Eligibility

Inclusion Criteria

Women must not be of child-bearing potential (1 year post-menopausal or surgically sterile).
Symptoms of acute MI of more than 30 min but less than 6 hours
New persistent ST-segment elevation ≥ 1 mm in two or more contiguous electrocardiogram (ECG) leads.

Exclusion Criteria

Expected time to 1st PCI balloon inflation in the hospital, from the qualifying ECG is more than 120 minutes
Contraindication to ticagrelor (refer to SmPC)
Concomitant medication that may increase the risk of bleeding [e.g non steroidal anti-inflammatory drugs (NSAIDs), oral anticoagulant and / or fibrinolytics, planned or administered 24 hours before randomization]
Any of the following conditions in the absence of a functioning implanted pacemaker: known SSS, second or third degree AVB, or documented syncope of suspected bradycardic origin.

Arm && Interventions

Group	Intervention	Description
Ticagrelor	Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
Placebo	Placebo	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Primary Outcome Measures

Name	Time	Method
Thrombolysis In Myocardial Infarction (TIMI) Flow Grade 3 of MI Culprit Vessel at Initial Angiography (Co-primary Endpoint)	At initial angiography, pre PCI	(TIMI) flow grade classification is used to assess coronary blood flow in acute coronary syndromes. grade 0:no reperfusion, grade 1: penetration without perfusion, grade 2: Partial reperfusion, grade 3: complete perfusion.
ST-segment Elevation Resolution Pre PCI ≥70% (Co-primary Endpoint)	Between baseline and PCI	ST segment elevation resolution is the mean ST elevation pre-hospital minus the mean STelevation pre-PCI divided by the mean ST elevation pre-hospital. It is expressed as a percentage and split in 2 categories , complete (≥70%) versus incomplete (\<70%) resolution.

Secondary Outcome Measures

Name	Time	Method
1st Composite Clinical Endpoint	during the 30 days of treatment	death/MI/stroke/urgent revascularization/stent thrombosis. Adjudicated events except death
2nd Composite Clinical Endpoint	within 30 days of study	Death/MI/urgent revascularization. Adjudicated events except death
Definite Stent Thrombosis	during 30 days of treatment	Definite stent thrombosis is considered to have occurred by either angiographic or pathologic confirmation. It is an adjudicated endpoint
TIMI Flow Grade 3 Post -PCI	at coroangiography post-PCI	TIMI) flow grade 3 is complete perfusion post-PCI.
ST Segment Elevation Resolution Post-PCI >= 70%	Between baseline and ECG 60 mn post-PCI	ST segment elevation resolution post PCI \>=70% is defined as complete resolution
Thrombotic Bail-out With GPIIb/IIIa Inhibitors at Initial PCI	during PCI	Glycoprotein (GP) IIb/IIIa inhibitors are often used as a rescue or bailout therapy to manage complications arising during percutaneous coronary intervention.
Major Bleeds Within 48 Hours	within 48 hours of first dose	non CABG related bleeds, (PLATO definition) include Life threatening and other major bleeds
Minor and Major Bleedings Within 48 Hours	within 48 hours of first dose	non CABG related bleeds (PLATO definition)
Major Bleeds After 48 Hours	after 48hours post-first dose	non CABG related bleeds (PLATO definition) include life threatening and other major bleedings
Minor and Major Bleeds After 48 Hours	after 48 hours post first dose	non CABG related bleeds (PLATO definition)