Dual Antiplatelet Therapy For Shock Patients With Acute Myocardial Infarction

Study Overview
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Brief Summary
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Multicenter randomized double blind trial comparing intravenous cangrelor and oral ticagrelor in patients with acute myocardial infarction complicated by initial cardiogenic shock and treated with primary angioplasty.

Detailed Description
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Randomization to study drugs shall be performed using an online database system for data collection; the assigned arm and the randomisation code will be generated after entering basic patient data based on a predefined randomization scheme. Concomitant therapy. Acetylsalicylic acid - 500 mg i.v. initial dose, and then 100 mg oral daily dose. Proton pump inhibitor. Additional therapies including further antithrombotic treatment (GP IIb/IIIa inhibitor, heparin) and mechanical support (IABP, ECMO) shall be fully in the competence of the treating doctor. Electronic database - eCRF. The data from individual follow-up assessments will be entered into an electronic database. The online instrument CLADE-IS will be used for data collection; this instrument provides robust options for electronic case report form (eCRF) design, hierarchical administration of user rights and a user-friendly web interface. The system provides predefined validation rules, conversions of variables, and it takes into account the relationships between variables; user access is controlled by the hierarchical system of user rights and user roles, and database operations are stored for the purpose of audits and tracking of changes. Data safety is ensured through physical security of the servers, authorised access and backup procedures. Laboratory collections. The efficacy of the antiaggregation drugs cangrelor and ticagrelor will be determined using the flow cytometry analysis of intracellular VASP (vasodilator-stimulated phosphoprotein) phosphorylation. Study Committees: Executive c., Steering c., Endpoint adjudication c., Data safety monitoring board. Monitoring. External monitor Clinical Research Associate (CRA) Definitions. Death is defined as death from all causes. Death from cardiovascular causes is defined as death with evidence of a cardiovascular cause or any death without clear evidence of a non-cardiovascular cause. All deaths are considered as cardiac unless a clear non-cardiac cause can be determined. Any unexpected death (for example, even in patients with a co-existing, potentially fatal non-cardiac disease - cancer, infection) is classified as a death from cardiovascular causes. Myocardial reinfarction is defined as a new (additional) MI that must differ from the MI based on which the patient was enrolled into the study, satisfying the Third Universal Definition of MI criteria. Urgent revascularisation of the infarct related artery is defined as a new emergent/urgent revascularisation of the artery intervened upon in the initial procedure, due to repeated manifestations of ischemia occurring after completion of the initial PCI. Stroke is defined as rapid onset of a new neurological deficit due to an ischemic or haemorrhagic lesion in the central nervous system with the symptoms lasting for at least 24 hours from their onset or resulting in death. Definitive stent thrombosis is defined according to the Academic Research Consortium criteria. Bleeding is defined according to the Bleeding Academic Research Consortium (BARC) criteria. External collaborating centre for statistical analyses. Institute of Biostatistics and Analyses at the Faculty of Medicine of the Masaryk University in Brno, Czech Republic

Official Title
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Cangrelor Versus Ticagrelor In Patients With Acute Myocardial Infarction Complicated With Initial Cardiogenic Shock

Conditions
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Acute Myocardial Infarction, Cardiogenic Shock

Intervention / Treatment
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* Drug: Cangrelor
* Drug: Ticagrelor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age over 18 years Acute myocardial infarction according to the definition of ESC/ACC/AHA, indicated for emergency percutaneous coronary intervention (primary PCI strategy) Cardiogenic shock present upon admission due to the AMI (≥ 2 of the criteria below are satisfied)24 sBP < 90 mmHg with the absence of hypovolemia Need of vasopressor and/or inotropic therapy Presence of the signs of the organ hypoperfusion - cyanosis, cold acra, disorder of consciousness, congestive heart failure Informed consent form signed. Exclusion Criteria: Contraindications of antiplatelet therapy with ticagrelor/cangrelor25 Recent (< 6 months) major bleeding Recent (< 1 month) major surgery/injury History of intracranial bleeding History of stroke/TIA Known intolerance to ticagrelor/cangrelor Severe impairment of hepatic function Concomitant administration of strong CYP3A4 inhibitors (for example, ketoconazole, clarithromycin, nefazodone, ritonavir and atazanavir) Administration of a loading dose of an oral P2Y12 inhibitor prior to admission (clopidogrel ≥ 300 mg, ticagrelor 180 mg, prasugrel 60 mg) Need of concomitant chronic anticoagulation therapy due to indications such as atrial fibrillation, artificial valve, thromboembolic disease, etc.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cangrelor therapy<br>Initiation of iv Cangrelor immediately upon arrival of the patient to the cardiac catheterization laboratory and after randomization into the study. | Drug: Cangrelor<br>* Cangrelor: IV bolus 30 μg/kg (application < 1 minute), immediately followed by continuous infusion in the dose of 4 μg/kg/min. To accelerate the initiation of therapy, tables containing calculations of the bolus dose in ml and the speed of infusion therapy for individual weights will be prepared. Cangrelor therapy will be stopped after circulatory stabilization - when sBP > 100 mmHg persists for one hour / when IABP will be terminated / when vasoactive treatment with norepinephrine, dopamine (in the dose ≥ 5 μg/kg/min) will be stopped, but not later than 4 hours after PCI 30 minutes before stopping Cangrelor infusion, administration of initial dose of crushed Ticagrelor 180 mg and then Ticagrelor maintenance dose 90 mg twice a day for 12 months.<br>* Other names: intravenous P2Y12 inhibitor;|
| Active Comparator: Ticagrelor therapy<br>Initial dose Ticagrelor immediately upon arrival of the patient to the cardiac catheterization laboratory and after randomization into the study. In patients with a disorder of consciousness, initial dose of Ticagrelor will be administered immediately after nasogastric tube insertion. | Drug: Ticagrelor<br>* Initial dose crushed Ticagrelor 180 mg. Maintenance dose Ticagrelor 90 mg twice daily for 12 months.<br>* Other names: oral P2Y12 inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Clinical Endpoint | Combined endpoint defined as Death/Myocardial infarction/Stroke | Within 30 days after randomization | 
| Primary Laboratory endpoint | Early achievement of efficient inhibition of ADP-induced platelet aggregation | Periprocedural (periPCI) period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Key secondary net-clinical endpoint | Death/Myocardial infarction/Urgent revascularization of the infarct-related artery /Stroke/Major bleeding BARC ≥ 3 | Within 30 days after randomization | 
| Key safety endpoint | Incidence of bleeding according to the BARC definition | Within 30 days after randomization | 
| Key secondary endpoint | Cardiovascular death/Myocardial infarction/Urgent revascularization/Heart failure | Within 30 days and one year after randomization | 
| Secondary endpoint | Individual components of the primary clinical endpoint | Within 30 days and one year after randomization | 
| Other secondary endpoint | Death from cardiovascular causes | Within 30 days and one year after randomization | 
| Secondary outcome | Definite stent thrombosis | Within 30 days after randomization | 
| Secondary safety outcome | Delaying the surgery due to bleeding | Within 30 days after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute myocardial infarction, Cardiogenic shock, Primary percutaneous coronary intervention, Dual antiplatelet therapy, Cangrelor, Ticagrelor