Add-on Cangrelor in STEMI-triggered Cardiac Arrest

NCT03273075 | Unknown Phase 4

• 1 other identifier: Cang 2016-003265-26
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

In patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary angioplasty (PCI) P2Y12 receptor (P2Y12r) inhibition should be achieved as soon as possible. Resuscitated STEMI-patients receiving targeted temperature management (TTM, therapeutic hypothermia) after cardiac arrest, however, show deteriorated and delayed early response to available oral P2Y12r inhibitors. Therapeutic hypothermia attenuates the drugs' effectiveness by reducing its gastrointestinal absorption and metabolic activation. Acute stent thrombosis is 5-fold increased after angioplasty following resuscitated cardiac arrest because of insufficient early platelet suppression. Thus, aggressive antiplatelet strategies are needed to achieve optimal platelet suppression during PCI in those patients. The first intravenous P2Y12r inhibitor, cangrelor, has recently received marketing authorization for the acute treatment of STEMI. We hypothesize that add-on antiplatelet therapy with intravenous Cangrelor on-top of standard dual anti platelet therapy (DAPT) with Prasugrel or Ticagrelor is superior to standard antiplatelet therapy alone in terms of suppressing ADP-dependent platelet activation in resuscitated STEMI-patients receiving TTM.

Conditions

Cardiopulmonary Arrest With Successful Resuscitation; ACS - Acute Coronary Syndrome; Hypothermia, Induced

Keywords

P2Y12r inhibitor; Cardiac Arrest; STEMI; HTPR

Outcome Measures

Primary Outcomes (1)

• Platelet reactivity at stent placement

  Platelet reactivity (ADP-dependent platelet inhibition) at the time of cardiac intervention (i.e. at the time of stent placement) measured by impedance aggregometry (Multiplate Analyzer; aggregation units/min, AU\*min)

  up to 4 hours; time from study drug administration (Cangrelor/Placebo) to stent placement

Secondary Outcomes (3)

• Platelet reactivity

  15 minutes, 30 minutes, 60 minutes, 120 minutes, 240 minutes, 12hours from administration of study drug.

• Platelet inhibition

  15 minutes, 30 minutes, 60 minutes, 120 minutes, 240 minutes, 12hours from administration of study drug.

• Maximum Plasma Concentration [Cmax]

  15 minutes, 30 minutes, 60 minutes, 120 minutes, 240 minutes, 12hours from administration of study drug.

Study Arms (4)

Prasugrel + Cangrelor

ACTIVE COMPARATOR

If eligible, assigned to this arm and without contraindications to prasugrel administration, patients will receive a loading dose of prasugrel (60 mg) via nasogastric tube as soon as possible after arrival at the emergency department. Afterwards a 30 micrograms (mcg)/kg iv bolus of cangrelor followed immediately by a 4 mcg/kg/min iv infusion (lasting for at least 2 hours or for the duration of the revascularization procedure, whichever is longer) will be administered.

Drug: Cangrelor; Drug: Prasugrel

Ticagrelor + Cangrelor

ACTIVE COMPARATOR

If eligible and assigned to this arm (i.e. patients who have contraindications against prasugrel (age \>75years, weight \<60kg, history of transient ischemic attack, ischemic stroke, intracranial bleeding, known allergy against prasugrel/Efient), patients will receive a loading dose of ticagrelor (180 mg) via nasogastric tube as soon as possible after arrival at the emergency department. Afterwards a 30 micrograms (mcg)/kg iv bolus of cangrelor followed immediately by a 4 mcg/kg/min iv infusion (lasting for at least 2 hours or for the duration of the revascularization procedure, whichever is longer) will be administered.

Drug: Cangrelor; Drug: Ticagrelor

Prasugrel + Placebo

PLACEBO COMPARATOR

If eligible, assigned to this arm and no contraindications to prasugrel, patients will receive a loading dose of prasugrel (60 mg) via nasogastric tube as soon as possible after arrival at the emergency department. Afterwards a 30 micrograms (mcg)/kg iv bolus of placebo (0.9% NaCl) followed immediately by a 4 mcg/kg/min iv infusion of placebo (0.9% NaCl) (lasting for at least 2 hours or for the duration of the revascularization procedure, whichever is longer) will be administered.

Drug: Placebo; Drug: Prasugrel

Ticagrelor + Placebo

PLACEBO COMPARATOR

If eligible and assigned to this arm (i.e. patients who have contraindications against prasugrel (age \>75years, weight \<60kg, history of transient ischemic attack, ischemic stroke, intracranial bleeding, known allergy against prasugrel/Efient), patients will receive a loading dose of ticagrelor (180 mg) via nasogastric tube as soon as possible after arrival at the emergency department. Afterwards a 30 micrograms (mcg)/kg iv bolus of placebo (0.9% NaCl) followed immediately by a 4 mcg/kg/min iv infusion placebo (0.9% NaCl) (lasting for at least 2 hours or for the duration of the revascularization procedure, whichever is longer) will be administered.

Drug: Placebo; Drug: Ticagrelor

Interventions

Cangrelor DRUG

The intervention comprises add-on Cangrelor infusion (administration in compliance with manufacturer instructions) in addition to and after administration of standard P2Y12-blocker (prasugrel or ticagrelor) therapy.

Prasugrel + Cangrelor; Ticagrelor + Cangrelor

Placebo DRUG

The intervention comprises add-on placebo infusion (0.9% NaCl) in addition to and after administration of standard P2Y12-blocker (prasugrel or ticagrelor) therapy as placebo comparator

Also known as: 0.9% NaCl

Prasugrel + Placebo; Ticagrelor + Placebo

Prasugrel DRUG

The intervention comprises the standard P2Y12-blocker prasugrel therapy if not contraindicated.

Prasugrel + Cangrelor; Prasugrel + Placebo

Ticagrelor DRUG

The intervention comprises the standard P2Y12-blocker ticagrelor therapy if prasugrel is contraindicated and no contraindication to ticagrelor is present.

Ticagrelor + Cangrelor; Ticagrelor + Placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-74 years
• comatose survivors of OHCA
• initial shockable rhythm (i.e. ventricular fibrillation or pulseless ventricular tachycardia)
• STEMI (post-ROSC electrocardiography)
• application of TTM;
• scheduled for PCI
• interval of \<10 min from cardiac arrest to initiation of cardiopulmonary
• resuscitation (no-flow interval); interval of \<60 min from initiation of cardiopulmonary resuscitation
• to ROSC (low-flow interval)
• eligible for treatment with standard loading doses of DAPT including
• aspirin and either prasugrel or ticagrelor.

You may not qualify if:

• Pregnant or breast-feeding patients
• Body weight \<60kg
• Response to verbal commands after ROSC
• (thus not eligible for TTM)
• Cardiac arrest due to: trauma, exsanguination, strangulation, smoke
• inhalation, drug overdose, electrocution, hanging or drowning, or intracranial hemorrhage
• Patients not
• achieving ROSC or subjected to an extracorporeal circulatory assist device
• Acute treatment with P2Y12r inhibitor other than prasugrel or ticagrelor
• Active bleeding or increased risk of bleeding because of irreversible coagulation disorders or due to recent major surgery/trauma or uncontrolled
• severe hypertension
• Known history of ischemic or hemorrhagic stroke or transient ischemic attack
• (TIA)
• Known history of severe hepatic impairment (Child Pugh C)
• Known history of severe renal impairment (creatinine clearance \<30mL/min)

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, Austria

RECRUITING

MeSH Terms

Conditions

Acute Coronary Syndrome; Hypothermia; Heart Arrest; ST Elevation Myocardial Infarction

Interventions

cangrelor; Saline Solution; Prasugrel Hydrochloride; Ticagrelor

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Alexander o: Spiel, Prof., MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexander O. Spiel, Prof., MD

CONTACT

+4314040039530; alexander.spiel@meduinwien.ac.at

Michael Schwameis, MD

CONTACT

+4314040019640; michael.schwameis@meduinwien.ac.at

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc.Prof. Priv.Doz. Dr.med.univ. Alexander Spiel

Study Record Dates

• First Submitted: August 23, 2017
• First Posted: September 6, 2017
• Study Start: September 1, 2017
• Primary Completion: May 1, 2021
• Study Completion: December 1, 2021
• Last Updated: September 13, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)