Dual Antiplatelet Therapy For Shock Patients With Acute Myocardial Infarction
- Conditions
- Acute Myocardial InfarctionCardiogenic Shock
- Interventions
- Registration Number
- NCT03551964
- Lead Sponsor
- Faculty Hospital Kralovske Vinohrady
- Brief Summary
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 605
-
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)
- 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
-
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.
-
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)
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cangrelor therapy Cangrelor 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. Ticagrelor therapy Ticagrelor 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.
- Primary Outcome Measures
Name Time Method Primary Laboratory endpoint At the end of primary percutaneous coronary intervention; Within 24 hours from randomization The periprocedural rate of onset and the proportion of patients who achieve effective\* P2Y12 platelet receptor inhibition defined by a Platelet Reactivity Index (PRI) value.
\*PRI less than 50% as measured by the vasodilator-stimulated phosphoprotein phosphorylation flow cytometric assayPrimary Clinical Endpoint Within 30 days after randomization The composite of all-cause death, myocardial infarction, or ischemic stroke expressed as a proportion of patients with any of these events.
- Secondary Outcome Measures
Name Time Method Key secondary efficacy endpoint Within 30 days and one year after randomization Death, myocardial infarction, urgent revascularization of the infarct-related artery, stent thrombosis, or ischemic stroke expressed as a proportion of patients with any of these events
Key secondary safety endpoint Within 30 days and one year after randomization Bleeding as defined by BARC type ≥ 3B, expressed as a proportion of patients with this event.
Secondary net-clinical endpoint Within 30 days and one year after randomization Death, myocardial infarction, urgent revascularization of the infarct-related artery, stroke, or major bleeding as defined by the BARC type ≥ 3B criteria expressed as a proportion of patients with any of these events.
Secondary efficacy endpoint Within 30 days and one year after randomization Cardiovascular death, myocardial infarction, urgent revascularization, and heart failure expressed as a proportion of patients with any of these events.
Secondary endpoint From randomization to end of index event hospitalization, within 3 months after randomization Duration of hospitalization\* in days
\*Intensive care unit stay and total hospital stayOther secondary outcome Within 30 days after randomization Delayed\* aortocoronary bypass surgery due to a risk of bleeding.
\*Assessed by the heart team, indicating aortocoronary bypass surgery.Other secondary efficacy endpoint Within 30 days and one year after randomization Death from cardiovascular causes, expressed as a proportion of patients with this event.
Other secondary endpoint Initial phase of index event hospitalization, within 7 days after randomization Maximum values of high-sensitive cardiac troponin in μg per liter
Secondary safety endpoint Within 30 days after randomization Bleeding as defined by BARC type ≥ 3B, expressed as a proportion of patients with this event.
Secondary laboratory endpoint 1 hour after primary PCI Effective\* P2Y12 platelet receptor inhibition defined by Platelet Reactivity Index (PRI) value
\*PRI less than 50% as measured by the vasodilator-stimulated phosphoprotein phosphorylation flow cytometric assaySecondary outcome From randomization to the end of vasoactive pharmacotherapy / mechanical circulatory support, within 30 days after randomization Duration of vasoactive pharmacotherapy and/or mechanical circulatory support in days
Trial Locations
- Locations (29)
University Hospital Kralovske Vinohrady
🇨🇿Prague, Please Select, Czechia
St. Anne's University Hospital Brno
🇨🇿Brno, Czechia
Department of Cardiology, University Hospital Brno-Bohunice
🇨🇿Brno, Czechia
Cardiology Department, Regional Hospital
🇨🇿Ceske Budejovice, Czechia
University Hospital Hradec Králové
🇨🇿Hradec Králové, Czechia
Cardiology department, Regional hospital
🇨🇿Jihlava, Czechia
Cardiocenter, Regional Hospital
🇨🇿Karlovy Vary, Czechia
Krajská nemocnice Liberec
🇨🇿Liberec, Czechia
University Hospital Olomouc
🇨🇿Olomouc, Czechia
University Hospital Ostrava
🇨🇿Ostrava, Czechia
Department of Cardiology, Regional Hospital,
🇨🇿Pardubice, Czechia
University Hospital Pilsen
🇨🇿Pilsen, Czechia
General University Hospital in Prague
🇨🇿Prague, Czechia
Institute of Clinical and Experimental Medicine
🇨🇿Prague, Czechia
Na Homolce Hospital
🇨🇿Prague, Czechia
Cardiocenter, Hospital Podlesi
🇨🇿Trinec, Czechia
Regional Hospital T. Bati
🇨🇿Zlin, Czechia
Masaryk Hospital
🇨🇿Ústí Nad Labem, Czechia
Département de Cardiologie, Hôpital Bichat Assistance Publique Hôpitaux de Paris
🇫🇷Paris, France
Pitié-Salpêtrière Hospital (AP-HP)
🇫🇷Paris, France
Heart Center Freiburg University
🇩🇪Freiburg, Germany
University Medical Centre
🇩🇪Mannheim, Germany
University Hospital Tübingen
🇩🇪Tübingen, Germany
Collegium Medicum University Hospital No. 1
🇵🇱Bydgoszcz, Poland
Jagiellonianan University, University Hospital Krakow
🇵🇱Kraków, Poland
Medical University of Warsaw
🇵🇱Warsaw, Poland
Middle-Slovak Institute of Cardiovascular Diseases
🇸🇰Banska Bystrica, Slovakia
Center of Interventional Neuroradiology and Endovascular Treatment
🇸🇰Bratislava, Slovakia
Cardiocentre
🇸🇰Nitra, Slovakia