Dual Antiplatelet Therapy For Shock Patients With Acute Myocardial Infarction

NCT03551964 | Completed Phase 4 DMC

• 2 other identifiers: 13062017-23-12018-002161-19
• Study Type: interventional
• Target: 605
• Locations: 5 countries
• Sites: 29

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.

Conditions

Acute Myocardial Infarction; Cardiogenic Shock

Keywords

Acute myocardial infarction; Cardiogenic shock; Primary percutaneous coronary intervention; Dual antiplatelet therapy; Cangrelor; Ticagrelor

Outcome Measures

Primary Outcomes (2)

• Primary Laboratory endpoint

  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 assay

  At the end of primary percutaneous coronary intervention; Within 24 hours from randomization

• Primary Clinical Endpoint

  The composite of all-cause death, myocardial infarction, or ischemic stroke expressed as a proportion of patients with any of these events.

  Within 30 days after randomization

Secondary Outcomes (14)

• Key secondary efficacy endpoint

  Within 30 days and one year after randomization

• Key secondary safety endpoint

  Within 30 days and one year after randomization

• Secondary net-clinical endpoint

  Within 30 days and one year after randomization

• Secondary efficacy endpoint

  Within 30 days and one year after randomization

• Secondary endpoint

  Within 30 days and one year after randomization

Other Outcomes (3)

• Cost analysis

  Within 30 day and one year after randomization

• MRI sub-study endpoints

  Within one year after randomization

• Echo sub-study endpoints

  Within one year after randomization

Study Arms (2)

Cangrelor therapy

EXPERIMENTAL

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.

Drug: Cangrelor

Ticagrelor therapy

ACTIVE COMPARATOR

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.

Drug: Ticagrelor

Interventions

Cangrelor DRUG

Cangrelor: IV bolus 30 µg/kg (application \< 1 minute) followed immediately by continuous infusion at 4 µg/kg. Tables to calculate bolus dose in ml and infusion (in ml per hour) rate for each body weight group will be prepared in advance and will be included in the study medication kit to accelerate treatment start. * Cangrelor treatment will be discontinued after circulatory stabilization (but no earlier than 2 hours after infusion initiation) i.e. after systolic Blood Pressure (sBP) is maintained at the level \> 100 mmHg for one hour after the end of IABK and/or vasoactive treatment is discontinued, but no later than 4 hours after PCI, * 30 minutes before the end of Cangrelor infusion, administration of Ticagrelor 180 mg (crushed tablets) and then dose 90 mg every 12 hours.

Also known as: intravenous P2Y12 inhibitor

Cangrelor therapy

Ticagrelor DRUG

Ticagrelor: 180 mg loading dose - crushed tablets, 2 x 90 mg maintenance dose

Also known as: oral P2Y12 inhibitor

Ticagrelor therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Faculty Hospital Kralovske Vinohrady: lead
• Charles University, Czech Republic: collaborator
• Masaryk University: collaborator
• Ministry of Health, Czech Republic: collaborator
• National Institute for Metabolic and Cardiovascular Disease Research: collaborator
• Institute of Hematology and Blood Transfusion, Czech Republic: collaborator
• BioVendor LM: collaborator

Study Sites (29)

University Hospital Kralovske Vinohrady

Prague, Please Select, 10034, Czechia

Location

St. Anne's University Hospital Brno

Brno, 656 91, Czechia

Location

Department of Cardiology, University Hospital Brno-Bohunice

Brno, Czechia

Location

Cardiology Department, Regional Hospital

České Budějovice, Czechia

Location

University Hospital Hradec Králové

Hradec Králové, 500 05, Czechia

Location

Cardiology department, Regional hospital

Jihlava, Czechia

Location

Cardiocenter, Regional Hospital

Karlovy Vary, Czechia

Location

Krajská nemocnice Liberec

Liberec, 460 63, Czechia

Location

University Hospital Olomouc

Olomouc, 77900, Czechia

Location

University Hospital Ostrava

Ostrava, 70852, Czechia

Location

Department of Cardiology, Regional Hospital,

Pardubice, Czechia

Location

University Hospital Pilsen

Pilsen, 304 60, Czechia

Location

General University Hospital in Prague

Prague, 12808, Czechia

Location

Institute of Clinical and Experimental Medicine

Prague, 14021, Czechia

Location

Na Homolce Hospital

Prague, 150 30, Czechia

Location

Cardiocenter, Hospital Podlesi

Třinec, Czechia

Location

Masaryk Hospital

Ústí nad Labem, 40011, Czechia

Location

Regional Hospital T. Bati

Zlín, 762 75, Czechia

Location

Département de Cardiologie, Hôpital Bichat Assistance Publique Hôpitaux de Paris

Paris, France

Location

Pitié-Salpêtrière Hospital (AP-HP)

Paris, France

Location

Heart Center Freiburg University

Freiburg im Breisgau, Germany

Location

University Medical Centre

Mannheim, Germany

Location

University Hospital Tübingen

Tübingen, 72076, Germany

Location

Collegium Medicum University Hospital No. 1

Bydgoszcz, Poland

Location

Jagiellonianan University, University Hospital Krakow

Krakow, Poland

Location

Medical University of Warsaw

Warsaw, Poland

Location

Middle-Slovak Institute of Cardiovascular Diseases

Banská Bystrica, Slovakia

Location

Center of Interventional Neuroradiology and Endovascular Treatment

Bratislava, Slovakia

Location

Cardiocentre

Nitra, Slovakia

Location

Related Publications (3)

• Motovska Z, Hlinomaz O, Mrozek J, Kala P, Geisler T, Hromadka M, Akin I, Precek J, Kettner J, Cervinka P, Montalescot G, Jarkovsky J, Belohlavek J, Bis J, Matejka J, Vodzinska A, Muzafarova T, Tomasov P, Schee A, Bartus S, Andrasova A, Olivier CB, Kovarik A, Ostadal P, Demlova R, Souckova L, Vulev I, Coufal Z, Kochman J, Marinov I, Kubica J, Ducrocq G, Karpisek M, Klimsa Z, Hudec M, Widimsky P, Bhatt DL, Group DS. Cangrelor versus crushed ticagrelor in patients with acute myocardial infarction and cardiogenic shock: rationale and design of the randomised, double-blind DAPT-SHOCK-AMI trial. EuroIntervention. 2024 Oct 21;20(20):e1309-e1318. doi: 10.4244/EIJ-D-24-00203.

  PMID: 39432252 BACKGROUND

• Filipescu R, Collins SP, Radu RI, Ben Gal T, Antohi L, Abdelhamid M, Geavlete O, Pana M, Farmakis D, Matei DC, Savarese G, Margineanu C, Polovina M, Miro O, Guz D, Palazzuoli A, Masip J, Adamo M, Ambrosy AP, Chioncel O. Therapeutic Advances in the Management of Cardiogenic Shock. Am J Ther. 2026 Jan 15. doi: 10.1097/MJT.0000000000002025. Online ahead of print.

  PMID: 41543923 DERIVED

• Connery A, Ahuja T, Katz A, Arnouk S, Zhu E, Papadopoulos J, Rao S, Merchan C. Antithrombotic Stewardship: Evaluation of Platelet Reactivity-Guided Cangrelor Dosing Using the VerifyNow Assay. J Cardiovasc Pharmacol. 2024 May 1;83(5):482-489. doi: 10.1097/FJC.0000000000001543.

  PMID: 38335531 DERIVED

MeSH Terms

Conditions

Shock, Cardiogenic

Interventions

cangrelor; Ticagrelor

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Shock

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Zuzana Motovska, MD, PhD.

  University Hospital Kralovske Vinohrady, Charles University, Prague, Czech Republic

  PRINCIPAL INVESTIGATOR

• Deepak L Bhatt, MD, MPH, MBA.

  Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Zuzana Motovska MD PHD

Study Record Dates

• First Submitted: May 29, 2018
• First Posted: June 11, 2018
• Study Start: August 1, 2018
• Primary Completion: February 19, 2024
• Study Completion: April 1, 2025
• Last Updated: April 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

SL (3); CZ (18); DE (3); PL (3); FR (2)