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)

AstraZeneca1,875 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

1,875

Conditions

Myocardial Infarction

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Thrombolysis In Myocardial Infarction (TIMI) Flow Grade 3 of MI Culprit Vessel at Initial Angiography (Co-primary Endpoint)

(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.

Time frame: At initial angiography, pre PCI

ST-segment Elevation Resolution Pre PCI ≥70% (Co-primary Endpoint)

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.

Time frame: Between baseline and PCI

Secondary Outcomes

1st Composite Clinical Endpoint

death/MI/stroke/urgent revascularization/stent thrombosis. Adjudicated events except death

Time frame: during the 30 days of treatment

2nd Composite Clinical Endpoint

Death/MI/urgent revascularization. Adjudicated events except death

Time frame: within 30 days of study

Definite Stent Thrombosis

Definite stent thrombosis is considered to have occurred by either angiographic or pathologic confirmation. It is an adjudicated endpoint

Time frame: during 30 days of treatment

TIMI Flow Grade 3 Post -PCI

TIMI) flow grade 3 is complete perfusion post-PCI.

Time frame: at coroangiography post-PCI

ST Segment Elevation Resolution Post-PCI >= 70%

ST segment elevation resolution post PCI \>=70% is defined as complete resolution

Time frame: Between baseline and ECG 60 mn post-PCI

Thrombotic Bail-out With GPIIb/IIIa Inhibitors at Initial PCI

Glycoprotein (GP) IIb/IIIa inhibitors are often used as a rescue or bailout therapy to manage complications arising during percutaneous coronary intervention.

Time frame: during PCI

Major Bleeds Within 48 Hours

non CABG related bleeds, (PLATO definition) include Life threatening and other major bleeds

Time frame: within 48 hours of first dose

Minor and Major Bleedings Within 48 Hours

non CABG related bleeds (PLATO definition)

Time frame: within 48 hours of first dose

Major Bleeds After 48 Hours

non CABG related bleeds (PLATO definition) include life threatening and other major bleedings

Time frame: after 48hours post-first dose

Minor and Major Bleeds After 48 Hours