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)

Study Overview
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Brief Summary
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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.

Official Title
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A 30 Day International, Randomized, Parallel-group, Double-blind, Placebo-controlled Phase IV Study to Evaluate Efficacy and Safety of Pre-hospital vs. In-hospital Initiation of Ticagrelor Therapy in STEMI Patients Planned for PCI.

Conditions
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Myocardial Infarction, Segment Elevation Myocardial Infarction (STEMI)

Intervention / Treatment
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* Drug: Ticagrelor
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ticagrelor<br>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. | Drug: Ticagrelor<br>* Oral Ticagrelor loading dose (180 mg) followed by matching placebo<br>|
| Experimental: Placebo<br>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. | Drug: Placebo<br>* Placebo followed by oral Ticagrelor loading dose (180 mg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | Between baseline and PCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1st Composite Clinical Endpoint | death/MI/stroke/urgent revascularization/stent thrombosis. Adjudicated events except death | during the 30 days of treatment | 
| 2nd Composite Clinical Endpoint | Death/MI/urgent revascularization. Adjudicated events except death | 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 | during 30 days of treatment | 
| TIMI Flow Grade 3 Post -PCI | TIMI) flow grade 3 is complete perfusion post-PCI. | at coroangiography post-PCI | 
| ST Segment Elevation Resolution Post-PCI >= 70% | ST segment elevation resolution post PCI >=70% is defined as complete resolution | 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. | during PCI | 
| Major Bleeds Within 48 Hours | non CABG related bleeds, (PLATO definition) include Life threatening and other major bleeds | within 48 hours of first dose | 
| Minor and Major Bleedings Within 48 Hours | non CABG related bleeds (PLATO definition) | within 48 hours of first dose | 
| Major Bleeds After 48 Hours | non CABG related bleeds (PLATO definition) include life threatening and other major bleedings | after 48hours post-first dose | 
| Minor and Major Bleeds After 48 Hours | non CABG related bleeds (PLATO definition) | after 48 hours post first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart attack, heart disease, cardiovascular disease, stroke, reperfusion, pre hospital settings, ticagrelor, Percutaneous Coronary Intervention