Dual Antiplatelet Therapy For Shock Patients With Acute Myocardial Infarction (DAPT-SHOCK-AMI)

Faculty Hospital Kralovske Vinohrady

Status and phase: Completed; Phase 4

Conditions: Cardiogenic Shock; Acute Myocardial Infarction

Treatments: Drug: Ticagrelor; Drug: Cangrelor

Study type: Interventional

Funder types: Other

Identifiers

NCT03551964

13062017-23-1

2018-002161-19 (EudraCT Number)

Details and patient eligibility

About

Multicenter, international, randomized, placebo-controlled, double-blind trial comparing intravenous cangrelor and crushed oral ticagrelor in patients with acute myocardial infarction complicated by initial cardiogenic shock (CS-AMI) and treated with primary angioplasty (PCI).

The Dual Antiplatelet Therapy For Shock Patients With Acute Myocardial Infarction (DAPT-SHOCK-AMI) trial tests the hypothesis that intravenous cangrelor is (a) more effective in terms of its rate of onset and the proportion of patients achieving effective periprocedural inhibition of ADP-induced platelet aggregation and (b) at least as effective as the recommended treatment of oral (crushed) ticagrelor in reducing major cardiovascular events in patients with initial CS-AMI indicated for primary PCI strategy.

Full description

Randomization to study drugs will be performed using an online database system for data collection. After entering basic patient data, the assigned arm and the randomization code will be generated based on a predefined randomization scheme.

Concomitant therapy includes acetylsalicylic acid: an initial intravenous dose of 500 mg, followed by a daily oral dose of 100 mg. A proton pump inhibitor is also recommended. Additional therapies, such as further antithrombotic treatments (e.g., GP IIb/IIIa inhibitors, heparin) and mechanical support (IABP, ECMO), remain fully within the competence of the treating physician.

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 considers the relationships between variables; user access is controlled by the hierarchical system of user rights and user roles, and database operations are stored for audits and tracking of changes. Data safety is ensured through physical security of the servers, authorized access, and backup procedures.

Laboratory collections. The efficacy of the antiplatelet drugs cangrelor and ticagrelor will be determined using 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 a death with evidence of a cardiovascular cause or any death without clear evidence of a non-cardiovascular cause. All deaths are considered cardiac unless a clear non-cardiac cause can be identified. Any unexpected death (for example, in patients with a co-existing, potentially fatal non-cardiac disease such as cancer or infection) is classified as a death from cardiovascular causes.

Myocardial reinfarction (MI) 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 universal definition of MI criteria.

Urgent revascularization of the infarct-related artery is defined as a new emergent/urgent revascularization of the artery that was intervened in during the initial procedure due to repeated manifestations of ischemia after the completion of the initial PCI.

Stroke is defined as the rapid onset of a new neurological deficit due to an ischemic or hemorrhagic lesion in the central nervous system, with symptoms lasting at least 24 hours from their onset or resulting in death.

Definitive stent thrombosis is defined according to the Academic Research Consortium criteria.

New heart failure is defined as a hospitalization or emergency check-up for heart failure in a doctor's office or emergency room that requires treatment.

Bleeding is defined according to the Bleeding Academic Research Consortium (BARC) criteria.

External collaborating centre for data-management and statistical analyses: Institute of Biostatistics and Analyses at the Faculty of Medicine of the Masaryk University in Brno, Czech Republic.

Enrollment: 605 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age over 18 years

2. Acute myocardial infarction according to the definition of ESC/ACC/AHA, indicated for emergency percutaneous coronary intervention (primary PCI strategy)

3. Cardiogenic shock present upon admission due to the AMI (≥ 2 of the criteria below are satisfied)

   1. sBP < 90 mmHg with the absence of hypovolemia
   2. Need of vasopressor and/or inotropic therapy
   3. Presence of the signs of the organ hypoperfusion - cyanosis, cold acra, disorder of consciousness, congestive heart failure

4. Informed consent form signed

5. Women of childbearing potential should be protected from pregnancy throughout the study (relevant for long-term use of ticagrelor). Suitable methods of contraception in this case include hormonal contraceptives, barrier methods, or complete withdrawal - as long as it is consistent with the patient's lifestyle.

Exclusion criteria

1. Contraindications of antiplatelet therapy with ticagrelor/cangrelor

   • 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)

2. Administration of a loading dose of an oral P2Y12 inhibitor prior to admission (clopidogrel ≥ 300 mg, ticagrelor 180 mg, prasugrel 60 mg)

3. Need of concomitant chronic anticoagulation therapy due to indications such as atrial fibrillation, artificial valve, thromboembolic disease, etc.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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605 participants in 2 patient groups

Cangrelor therapy

Experimental group

Description:

IV Cangrelor is initiated immediately after the patient arrives at the 24/7 PCI center (cathlab, coronary/intensive care unit, other parts of department) and is randomized to the study.

Treatment:

Drug: Cangrelor

Ticagrelor therapy

Active Comparator group

Description:

The patient will receive the initial dose of crushed Ticagrelor immediately after arriving at the 24/7 PCI center (cath lab, coronary/intensive care unit, other parts of the department) and after being randomly assigned to the study; in patients with a disorder of consciousness, the initial dose will be administered immediately after the nasogastric tube is inserted.

Treatment:

Drug: Ticagrelor