Evaluation of Myocardial Reperfusion After Primary PCI in Patients With High Platelet Reactivity Treated by Cangrelor or Not

Study Overview
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Brief Summary
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This study aims to evaluate the impact on myocardial reperfusion and residual thrombotic burden of adding Cangrelor -a potent and immediate P2Y12 inhibitor- to ticagrelor in primary PCI patients with high on ticagrelor platelet reactivity compared to standard of care with ticagrelor alone.

Detailed Description
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Despite the use of potent P2Y12 inhibitor such as ticagrelor, half of the patients presented high platelet reactivity (HPR) at the time of primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). HPR has been associated with impaired myocardial reperfusion. Myocardial reperfusion, assessed using myocardial blush grade, is a strong prognostic factor associated with infarct size and mortality. Antiplatelet therapy intensification using a potent and immediate P2Y12 inhibitor such as Cangrelor according a point-of-care platelet function test has not been studied in the acute phase of STEMI. This study aims to evaluate the impact on myocardial reperfusion and residual thrombotic burden of adding Cangrelor to ticagrelor in primary PCI patients with high on ticagrelor platelet reactivity compared to standard of care with ticagrelor alone.

Official Title
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Evaluation of Myocardial Reperfusion and Residual Thrombotic Burden After Primary PCI for STEMI in Patients With High on Ticagrelor Platelet Reactivity Treated by IV Cangrelor Versus Ticagrelor Alone

Conditions
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ST-elevation Myocardial Infarction

Intervention / Treatment
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* Drug: cangrelor perfusion during PCI
* Procedure: standard PCI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient admitted for STEMI within 24 hours from symptom onset pretreated with ticagrelor, aspirin and enoxaparin (according local protocol) successfully treated by primary PCI of a native coronary culprit lesion anatomy accessible to optical coherence tomography (OCT or OFDI) Exclusion Criteria: cardiogenic shock stent restenosis or thrombosis use of glycoprotein IIb/IIIa inhibitors before or during PCI known coagulation disease high bleeding risk (thrombocytopenia <100,000/dL, surgery <30 days, active bleeding) uncontrolled arterial hypertension (>180/110 mmHg) history of stroke (ischemic or hemorrhagic) or transient ischemic attack known severe renal insufficiency (eGFR <30 ml/min) oral anticoagulation

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: patients without HPR<br>standard primary PCI | Procedure: standard PCI<br>* primary PCI without cangrelor<br>|
| Experimental: patients with HPR randomized to cangrelor<br>Cangrelor perfusion started before PCI | Drug: cangrelor perfusion during PCI<br>* Cangrelor perfusion (started before PCI) with intravenous bolus of 30 microgram/kg, followed by a perfusion of 4 microgram/kg/min during 2 hours or until the end of the PCI if longer<br>|
| Placebo Comparator: patients with HPR randomized to standard of care<br>standard primary PCI | Procedure: standard PCI<br>* primary PCI without cangrelor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade of myocardial blush | myocardial blush grade from 0 to 3 (normal) | during procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of residual thrombus burden | intrastent residual thrombus burden assessed by optical coherence tomography | during procedure | 
| measure of platelet reactivity | Platelet reactivity using VerifyNow after PCI for patients with basal platelet reaction unit>208 | during procedure | 
| troponin | peak value | day 1 | 
| infarct size and no reflow on MRI |  | during hospitalization assessed up to 7 days | 
| clinical outcomes | death, new myocardial infarction, stent thrombosis, new revascularization, stroke, major bleeding | during hospitalization assessed up to 7 days |