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Add-on Cangrelor in STEMI-triggered Cardiac Arrest

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ClinicalTrials.gov Identifier: NCT03273075
Recruitment Status : Recruiting
First Posted : September 6, 2017
Last Update Posted : September 13, 2017
Sponsor:
Information provided by (Responsible Party):
Alexander Spiel, Medical University of Vienna

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.

Condition or disease Intervention/treatment Phase
Cardiopulmonary Arrest With Successful Resuscitation ACS - Acute Coronary Syndrome Hypothermia, Induced Drug: Cangrelor Drug: Placebo Drug: Prasugrel Drug: Ticagrelor Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pharmacokinetic/Pharmacodynamic Effects of add-on Antiplatelet Therapy With Parenteral Cangrelor as Compared to Standard Dual Antiplatelet Treatment in Patients With ST-elevation Myocardial Infarction Complicated by Out-of-hospital Cardiac Arrest and Treated With Targeted Temperature Management
Estimated Study Start Date : September 2017
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cardiac Arrest

Arm Intervention/treatment
Active Comparator: Prasugrel + Cangrelor
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
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.

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

Active Comparator: Ticagrelor + Cangrelor
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
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.

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

Placebo Comparator: Prasugrel + Placebo

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
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
Other Name: 0.9% NaCl

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

Placebo Comparator: Ticagrelor + Placebo

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
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
Other Name: 0.9% NaCl

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




Primary Outcome Measures :
  1. Platelet reactivity at stent placement [ Time Frame: up to 4 hours; time from study drug administration (Cangrelor/Placebo) to 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)


Secondary Outcome Measures :
  1. Platelet reactivity [ Time Frame: 15 minutes, 30 minutes, 60 minutes, 120 minutes, 240 minutes, 12hours from administration of study drug. ]
    Platelet reactivity at baseline, 15 minutes, 30 minutes, 60minutes, 120 minutes, 240 minutes and 12 hours after study drug administration (Multiplate Analyzer, AU*min; VASP assay, platelet reactivity units PRU; PFA-100, closure time, CT).

  2. Platelet inhibition [ Time Frame: 15 minutes, 30 minutes, 60 minutes, 120 minutes, 240 minutes, 12hours from administration of study drug. ]
    Onset of ADP-dependent platelet inhibition (Multiplate Analyzer, VASP assay, PFA-100).

  3. Maximum Plasma Concentration [Cmax] [ Time Frame: 15 minutes, 30 minutes, 60 minutes, 120 minutes, 240 minutes, 12hours from administration of study drug. ]
    Prasugrel/Ticagrelor/Cangrelor metabolites will be measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at the time of stent placement, 15minutes, 30 minutes, 60 minutes, 120 minutes, 240 minutes and 12 hours after study drug administration



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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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)
  • Hypersensitivity to the active substance or to any of the excipients
  • Terminal illness present before cardiac arrest
  • Thrombolysis therapy
  • Scheduled for coronary bypass surgery (CABG)
  • Prior P2Y12r inhibitor use in the past 7 days
  • Prior vitamin K antagonists/NOACs use in past 7 days
  • Patients with known allergic reaction to P2Y12r inhibitors.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03273075


Contacts
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Contact: Alexander O. Spiel, Prof., MD +4314040039530 alexander.spiel@meduinwien.ac.at
Contact: Michael Schwameis, MD +4314040019640 michael.schwameis@meduinwien.ac.at

Locations
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Austria
Medical University of Vienna Recruiting
Vienna, Austria
Contact: Alexander O Spiel, MD         
Sponsors and Collaborators
Medical University of Vienna
Investigators
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Principal Investigator: Alexander o: Spiel, Prof., MD Medical University of Vienna

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Responsible Party: Alexander Spiel, Assoc.Prof. Priv.Doz. Dr.med.univ. Alexander Spiel, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT03273075     History of Changes
Other Study ID Numbers: Cang 2016-003265-26
First Posted: September 6, 2017    Key Record Dates
Last Update Posted: September 13, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Alexander Spiel, Medical University of Vienna:
P2Y12r inhibitor
Cardiac Arrest
STEMI
HTPR

Additional relevant MeSH terms:
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Platelet Aggregation Inhibitors
Acute Coronary Syndrome
Heart Arrest
Hypothermia
ST Elevation Myocardial Infarction
Out-of-Hospital Cardiac Arrest
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Body Temperature Changes
Signs and Symptoms
Myocardial Infarction
Ticagrelor
Prasugrel Hydrochloride
Cangrelor
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs