Dual Antiplatelet Therapy For Shock Patients With Acute Myocardial Infarction

Acute Myocardial Infarction Clinical Trial

— DAPT-SHOCK-AMI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03551964
• Other study ID #: 13062017-23-1
• Secondary ID: 2018-002161-19
• Status: Recruiting
• Phase: Phase 4
• Start date: August 1, 2018
• Est. completion date: January 2025

Study information

• Verified date: January 2024
• Source: Faculty Hospital Kralovske Vinohrady
• Contact: Zuzana Motovska, MD. PhD.
• Phone: +420731573253
• Email: motovska.zuzana[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 550
• Est. completion date: January 2025
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)24

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.

Exclusion Criteria:

1. 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)

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.

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Cardiogenic Shock
• Infarction
• Myocardial Infarction
• Shock
• Shock, Cardiogenic

Intervention

Drug:
• Cangrelor
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.
• Ticagrelor
Initial dose crushed Ticagrelor 180 mg. Maintenance dose Ticagrelor 90 mg twice daily for 12 months.

Locations

Country	Name	City	State
Czechia	Department of Cardiology, University Hospital Brno-Bohunice	Brno
Czechia	St. Anne's University Hospital Brno	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	University Hospital Kralovske Vinohrady	Prague	Please Select
Czechia	Cardiocenter, Hospital Podlesi	Trinec
Czechia	Masaryk Hospital	Ústí Nad Labem
Czechia	Regional Hospital T. Bati	Zlin
France	Département de Cardiologie, Hôpital Bichat Assistance Publique Hôpitaux de Paris	Paris
France	Pitié-Salpêtrière Hospital (AP-HP)	Paris
Germany	Heart Center Freiburg University	Freiburg
Germany	University Medical Centre	Mannheim
Germany	University Hospital Tübingen	Tübingen
Poland	Collegium Medicum University Hospital No. 1	Bydgoszcz
Poland	Jagiellonianan University, University Hospital Krakow	Kraków
Poland	Medical University of Warsaw	Warsaw
Slovakia	Middle-Slovak Institute of Cardiovascular Diseases	Banska Bystrica
Slovakia	Center of Interventional Neuroradiology and Endovascular Treatment	Bratislava
Slovakia	Cardiocentre	Nitra

Sponsors (2)

Lead Sponsor	Collaborator
Faculty Hospital Kralovske Vinohrady	Charles University, Czech Republic

Countries where clinical trial is conducted

Czechia,  France,  Germany,  Poland,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pre-specified Outcome	Duration of vasoactive pharmacotherapy and/or mechanical circulatory support	Index event Hospitalization
Other	Other Pre-specified Outcome	Duration of hospitalisation	Index event Hospitalization
Other	Cost analysis	Cost-effectiveness analysis	Within 30 day and one year after randomization
Other	MRI sub-study endpoints	Magnetic Resonance Imaging sub-study	Within one year after randomization
Primary	Primary Clinical Endpoint	Combined endpoint defined as Death/Myocardial infarction/Stroke	Within 30 days after randomization
Primary	Primary Laboratory endpoint	Early achievement of efficient inhibition of ADP-induced platelet aggregation	Periprocedural (periPCI) period
Secondary	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
Secondary	Key safety endpoint	Incidence of bleeding according to the BARC definition	Within 30 days after randomization
Secondary	Key secondary endpoint	Cardiovascular death/Myocardial infarction/Urgent revascularization/Heart failure	Within 30 days and one year after randomization
Secondary	Secondary endpoint	Individual components of the primary clinical endpoint	Within 30 days and one year after randomization
Secondary	Other secondary endpoint	Death from cardiovascular causes	Within 30 days and one year after randomization
Secondary	Secondary outcome	Definite stent thrombosis	Within 30 days after randomization
Secondary	Secondary safety outcome	Delaying the surgery due to bleeding	Within 30 days after randomization