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

Sponsor

Faculty Hospital Kralovske Vinohrady (Other)

Overall Status

Recruiting

CT.gov ID

NCT03551964

Collaborator

Charles University, Czech Republic (Other)

304

Enrollment

Locations

Arms

Anticipated Duration (Months)

14.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myocardial Infarction Cardiogenic Shock	Drug: Cangrelor Drug: Ticagrelor	Phase 4

Detailed 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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

304 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 1, 2018

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

May 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cangrelor therapy Initiation of iv Cangrelor immediately upon arrival of the patient to the cardiac catheterization laboratory and after randomization into the study.	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. Other Names: intravenous P2Y12 inhibitor
Active Comparator: Ticagrelor therapy Initial dose Ticagrelor immediately upon arrival of the patient to the cardiac catheterization laboratory and after randomization into the study. In patients with a disorder of consciousness, initial dose of Ticagrelor will be administered immediately after nasogastric tube insertion.	Drug: Ticagrelor Initial dose crushed Ticagrelor 180 mg. Maintenance dose Ticagrelor 90 mg twice daily for 12 months. Other Names: oral P2Y12 inhibitor

Arm

Intervention/Treatment

Experimental: Cangrelor therapy

Initiation of iv Cangrelor immediately upon arrival of the patient to the cardiac catheterization laboratory and after randomization into the study.

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.

Other Names:

intravenous P2Y12 inhibitor

Active Comparator: Ticagrelor therapy

Initial dose Ticagrelor immediately upon arrival of the patient to the cardiac catheterization laboratory and after randomization into the study. In patients with a disorder of consciousness, initial dose of Ticagrelor will be administered immediately after nasogastric tube insertion.

Drug: Ticagrelor

Initial dose crushed Ticagrelor 180 mg. Maintenance dose Ticagrelor 90 mg twice daily for 12 months.

Other Names:

oral P2Y12 inhibitor

Outcome Measures

Primary Outcome Measures

Clinical endpoint [Within 30 days after randomization]
Combined endpoint defined as Death/Myocardial infarction/Stroke
Laboratory endpoint [Periprocedural (periPCI) period]
Early achievement of efficient inhibition of ADP-induced platelet aggregation. Efficient inhibition is defined by the Platelet Reactivity Index (determined based on the VASP protein phosphorylation) < 50%.

Secondary Outcome Measures

Key secondary net-clinical endpoint [Within 30 days after randomization]
Death/Myocardial infarction/Urgent revascularisation of the infarct-related artery /Stroke/Major bleeding BARC ≥ 3
Key safety endpoint [Within 30 days after randomization]
Incidence of bleeding according to the BARC definition
Other secondary endpoint [Within 30 days and one year after randomization]
Individual components of the primary clinical endpoint
Other secondary endpoint [Within 30 days and one year after randomization.]
Death from cardiovascular causes
Secondary endpoint [Within 30 days after randomization]
Definite stent thrombosis
Secondary endpoint [Within 30 days after randomization]
Duration of vasoactive pharmacotherapy and/or mechanical circulatory support (norepinephrine/epinephrine/dopamine in the dose > 5 μg/kg/min/IABP/ECMO),
Secondary endpoint [Index event Hospitalization]
Duration of hospitalisation
Secondary endpoint [Within 30 days after randomization]
Delaying the surgery due to bleeding

Other Outcome Measures

Cost analysis [Within 30 day after randomization]
Cost-effectiveness analysis
MRI sub-study [Within one year after randomization]
Magnetic Resonance Imaging sub-study

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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)24
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.

Exclusion Criteria:

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)

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Kralovske Vinohrady	Prague	Please Select	Czechia	10034
2	St. Anne's University Hospital Brno	Brno		Czechia	656 91
3	Department of Cardiology, University Hospital Brno-Bohunice	Brno		Czechia
4	Cardiology Department, Regional Hospital	Ceske Budejovice		Czechia
5	University Hospital Hradec Králové	Hradec Králové		Czechia	500 05
6	Cardiology department, Regional hospital	Jihlava		Czechia
7	Cardiocenter, Regional Hospital	Karlovy Vary		Czechia
8	Krajská nemocnice Liberec	Liberec		Czechia	460 63
9	University Hospital Olomouc	Olomouc		Czechia	77900
10	University Hospital Ostrava	Ostrava		Czechia	70852
11	Department of Cardiology, Regional Hospital,	Pardubice		Czechia
12	University Hospital Pilsen	Pilsen		Czechia	304 60
13	General University Hospital in Prague	Prague		Czechia	12808
14	Institute of Clinical and Experimental Medicine	Prague		Czechia	14021
15	Na Homolce Hospital	Prague		Czechia	150 30
16	Cardiocenter, Hospital Podlesi	Trinec		Czechia
17	Regional Hospital T. Bati	Zlin		Czechia	762 75
18	Masaryk Hospital	Ústí Nad Labem		Czechia	40011
19	Middle-Slovak Institute of Cardiovascular Diseases	Banska Bystrica		Slovakia
20	Center of Interventional Neuroradiology and Endovascular Treatment	Bratislava		Slovakia
21	Cardiocentre	Nitra		Slovakia