Dual Antiplatelet Therapy For Shock Patients With Acute Myocardial Infarction

NCT ID: NCT03551964

Last Updated: 2025-04-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 605 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-01
• Study Completion Date: 2025-04-01

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.

Conditions

Acute Myocardial Infarction; Cardiogenic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cangrelor therapy

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.

Group Type: EXPERIMENTAL

Cangrelor

Intervention Type: 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.

Ticagrelor therapy

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.

Group Type: ACTIVE_COMPARATOR

Ticagrelor

Intervention Type: DRUG

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

Interventions

Cangrelor

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.

Intervention Type: DRUG

Ticagrelor

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

Intervention Type: DRUG

Other Intervention Names

intravenous P2Y12 inhibitor; oral P2Y12 inhibitor

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Charles University, Czech Republic

OTHER

Sponsor Role: collaborator

Masaryk University

OTHER

Sponsor Role: collaborator

Ministry of Health, Czech Republic

OTHER_GOV

Sponsor Role: collaborator

National Institute for Metabolic and Cardiovascular Disease Research

UNKNOWN

Sponsor Role: collaborator

Institute of Hematology and Blood Transfusion, Czech Republic

OTHER

Sponsor Role: collaborator

BioVendor LM

UNKNOWN

Sponsor Role: collaborator

Faculty Hospital Kralovske Vinohrady

OTHER_GOV

Sponsor Role: lead

Responsible Party

Zuzana Motovska

Zuzana Motovska MD PHD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zuzana Motovska, MD, PhD.

Role: PRINCIPAL_INVESTIGATOR

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

Deepak L Bhatt, MD, MPH, MBA.

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

České Budějovice, , 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

Třinec, , Czechia

Masaryk Hospital

Ústí nad Labem, , Czechia

Regional Hospital T. Bati

Zlín, , 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 im Breisgau, , Germany

University Medical Centre

Mannheim, , Germany

University Hospital Tübingen

Tübingen, , Germany

Collegium Medicum University Hospital No. 1

Bydgoszcz, , Poland

Jagiellonianan University, University Hospital Krakow

Krakow, , Poland

Medical University of Warsaw

Warsaw, , Poland

Middle-Slovak Institute of Cardiovascular Diseases

Banská Bystrica, , Slovakia

Center of Interventional Neuroradiology and Endovascular Treatment

Bratislava, , Slovakia

Cardiocentre

Nitra, , Slovakia

Countries

Czechia; France; Germany; Poland; Slovakia

References

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.

Reference Type: BACKGROUND

PMID: 39432252 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38335531 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-002161-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

13062017-23-1

Identifier Type: -

Identifier Source: org_study_id