Clinical trial NCT03551964: Dual Antiplatelet Therapy For Shock Patients With Acute Myocardial Infarction
Official title: Cangrelor Versus Ticagrelor In Patients With Acute Myocardial Infarction Complicated With Initial Cardiogenic Shock
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Myocardial Infarction
Cardiogenic Shock
Keywords: Acute myocardial infarction
Cardiogenic shock
Primary percutaneous coronary intervention
Dual antiplatelet therapy
Cangrelor
Ticagrelor
Lead sponsor: Faculty Hospital Kralovske Vinohrady
Sponsor class: OTHER_GOV
Collaborators: name: Charles University, Czech Republic
name: Masaryk University
name: Ministry of Health, Czech Republic
name: National Institute for Metabolic and Cardiovascular Disease Research
name: Institute of Hematology and Blood Transfusion, Czech Republic
name: BioVendor LM
First posted: 2018-06-11
Enrollment: 605
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Primary Laboratory endpoint
timeFrame: At the end of primary percutaneous coronary intervention; Within 24 hours from randomization
measure: Primary Clinical Endpoint
timeFrame: Within 30 days after randomization
Secondary outcomes:
measure: Key secondary efficacy endpoint
timeFrame: Within 30 days and one year after randomization
measure: Key secondary safety endpoint
timeFrame: Within 30 days and one year after randomization
measure: Secondary net-clinical endpoint
timeFrame: Within 30 days and one year after randomization
measure: Secondary efficacy endpoint
timeFrame: Within 30 days and one year after randomization
measure: Secondary endpoint
timeFrame: Within 30 days and one year after randomization
measure: Other secondary outcome
timeFrame: Within 30 days and one year after randomization
measure: Other secondary efficacy endpoint
timeFrame: Within 30 days and one year after randomization
measure: Other secondary endpoint
timeFrame: Within 30 days after randomization
measure: Secondary safety endpoint
timeFrame: Within 30 days after randomization
measure: Other secondary outcome
timeFrame: Within 30 days after randomization
measure: Secondary laboratory endpoint
timeFrame: 1 hour after primary PCI
measure: Secondary endpoint
timeFrame: From randomization to end of index event hospitalization, within 3 months after randomization
measure: Other secondary endpoint
timeFrame: Initial phase of index event hospitalization, within 7 days after randomization
measure: Secondary outcome
timeFrame: From randomization to the end of vasoactive pharmacotherapy / mechanical circulatory support, within 30 days after randomization
Other outcomes:
measure: Cost analysis
timeFrame: Within 30 day and one year after randomization
measure: MRI sub-study endpoints
timeFrame: Within one year after randomization
measure: Echo sub-study endpoints
timeFrame: Within one year after randomization
Locations:
city: Prague
country: Czechia
facility: University Hospital Kralovske Vinohrady
state: Please Select
city: Brno
country: Czechia
facility: St. Anne's University Hospital Brno
city: Brno
country: Czechia
facility: Department of Cardiology, University Hospital Brno-Bohunice
city: Ceske Budejovice
country: Czechia
facility: Cardiology Department, Regional Hospital
city: Hradec Králové
country: Czechia
facility: University Hospital Hradec Králové
city: Jihlava
country: Czechia
facility: Cardiology department, Regional hospital
city: Karlovy Vary
country: Czechia
facility: Cardiocenter, Regional Hospital
city: Liberec
country: Czechia
facility: Krajská nemocnice Liberec
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
city: Ostrava
country: Czechia
facility: University Hospital Ostrava
city: Pardubice
country: Czechia
facility: Department of Cardiology, Regional Hospital,
city: Pilsen
country: Czechia
facility: University Hospital Pilsen
city: Prague
country: Czechia
facility: General University Hospital in Prague
city: Prague
country: Czechia
facility: Institute of Clinical and Experimental Medicine
city: Prague
country: Czechia
facility: Na Homolce Hospital
city: Trinec
country: Czechia
facility: Cardiocenter, Hospital Podlesi
city: Zlin
country: Czechia
facility: Regional Hospital T. Bati
city: Ústí Nad Labem
country: Czechia
facility: Masaryk Hospital
city: Paris
country: France
facility: Département de Cardiologie, Hôpital Bichat Assistance Publique Hôpitaux de Paris
city: Paris
country: France
facility: Pitié-Salpêtrière Hospital (AP-HP)
city: Freiburg
country: Germany
facility: Heart Center Freiburg University
city: Mannheim
country: Germany
facility: University Medical Centre
city: Tübingen
country: Germany
facility: University Hospital Tübingen
city: Bydgoszcz
country: Poland
facility: Collegium Medicum University Hospital No. 1
city: Kraków
country: Poland
facility: Jagiellonianan University, University Hospital Krakow
city: Warsaw
country: Poland
facility: Medical University of Warsaw
city: Banska Bystrica
country: Slovakia
facility: Middle-Slovak Institute of Cardiovascular Diseases
city: Bratislava
country: Slovakia
facility: Center of Interventional Neuroradiology and Endovascular Treatment
city: Nitra
country: Slovakia
facility: Cardiocentre
Study officials:
affiliation: University Hospital Kralovske Vinohrady, Charles University, Prague, Czech Republic
name: Zuzana Motovska, MD, PhD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA
name: Deepak L Bhatt, MD, MPH, MBA.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.