Cangrelor in Comatose Survivors of OHCA Undergoing Primary PCI

NCT04005729 | Completed Phase 4

• 1 other identifier: KOIIM-2019-1
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of the trial is to find out if 4-hour continuous infusion of parenteral P2Y12 inhibitor cangrelor at the start of primary percutaneous coronary intervention (PCI) immediately and effectively suppresses platelet activity in comatose survivors of out-of-hospital cardiac arrest (OHCA). Half of the participants will receive the standard care of dual antiplatelet therapy - acetysalicylic acid and ticagrelor tablets via nasogastric or orogastric tube and the other half the standard care with additional cangrelor infusion at the start of the PCI.

Conditions

Out-Of-Hospital Cardiac Arrest; Acute Coronary Syndrome

Keywords

cangrelor; P2Y12; out-of-hospital cardiac arrest; induced hypothermia; primary percutaneous coronary intervention

Outcome Measures

Primary Outcomes (7)

• VerifyNow P2Y12Test - Platelet Reactivity

  Platelet inhibition measured by VerifyNow as P2Y12 reaction units (PRU). Platelet reactivity reflects P2Y12 inhibitor effect with higher PRU values showing low P2Y12 response and lower values decreased platelet reactivity due to the effect of a P2Y12 inhibitor. High on-treatment platelet reactivity was defined as \>208 PRU.

  1 hour after the start of cangrelor infusion/1 hour after the start of PPCI in controls

• VerifyNow P2Y12Test - Platelet Reactivity

  Platelet inhibition measured by VerifyNow as P2Y12 reaction units (PRU). Platelet reactivity reflects P2Y12 inhibitor effect with higher PRU values showing low P2Y12 response and lower values decreased platelet reactivity due to the effect of a P2Y12 inhibitor. High on-treatment platelet reactivity was defined as \>208 PRU.

  3 hours after the start of cangrelor infusion/3 hours after the start of PPCI in controls

• VerifyNow P2Y12Test - Platelet Reactivity

  Platelet inhibition measured by VerifyNow as P2Y12 reaction units (PRU). Platelet reactivity reflects P2Y12 inhibitor effect with higher PRU values showing low P2Y12 response and lower values decreased platelet reactivity due to the effect of a P2Y12 inhibitor. High on-treatment platelet reactivity was defined as \>208 PRU.

  5 hours after the start of cangrelor infusion/5 hours after the start of PPCI in controls

• Multiplate ADP test

  Platelet activation by adenosine diphosphate (ADP) expressed in arbitrary aggregation units (U). P2Y12 inhibitors block ADP receptors and decrease platelet activation by ADP. Higher values mean less effect of P2Y12 inhibitors, lower values mean more effect of P2Y12 inhibitors on platelets. High on-treatment platelet reactivity was defined as \>46 U.

  1 hour after the start of cangrelor infusion/1 hour after the start of PPCI in controls

• Multiplate ADP test

  Platelet activation by adenosine diphosphate (ADP) expressed in arbitrary aggregation units (U). P2Y12 inhibitors block ADP receptors and decrease platelet activation by ADP. Higher values mean less effect of P2Y12 inhibitors, lower values mean more effect of P2Y12 inhibitors on platelets. High on-treatment platelet reactivity was defined as \>46 U.

  3 hours after the start of cangrelor infusion/3 hours after the start of PPCI in controls

• Multiplate ADP test

  Platelet activation by adenosine diphosphate (ADP) expressed in arbitrary aggregation units (U). P2Y12 inhibitors block ADP receptors and decrease platelet activation by ADP. Higher values mean less effect of P2Y12 inhibitors, lower values mean more effect of P2Y12 inhibitors on platelets. High on-treatment platelet reactivity was defined as \>46 U.

  5 hours after the start of cangrelor infusion/5 hours after the start of PPCI in controls

• BARC score or the need for discontinuation of cangrelor infusion

  Standardized bleeding definition as described by Bleeding Academic Research Consortium (BARC). Type 0: no bleeding. 1. actionable bleeding, does not require treatment by attending physician. 2. any overt, actionable sign of hemorrhage plus at least one criteria: (1) requiring nonsurgical, medical intervention, (2) leading to increased level of care, or (3) prompting evaluation. 3. overt bleeding plus (1) haemoglobin drop of more than 3 g/dL or need for transfusion, (2) cardiac tamponade, (3) requiring surgical intervention, (4) intracranial hemorrhage (does not include microbleeds or hemorrhagic transformation, does include intraspinal), (5) intraocular bleed compromising vision. 4. CABG-related bleeding (not applicable). 5. Fatal bleeding: (1) probable - clinically suspicious, (2) definite - overt bleeding or autopsy or imaging confirmation. Significant bleeding will be defined as BARC 2, 3 and 5 or the need for discontinuation of cangrelor infusion.

  During the cangrelor infusion and up to 5 hours after the PCI

Secondary Outcomes (5)

• Angiographic result - final TIMI flow

  Angiography review within 24 hours of P-PCI (the following day)

• Rate of stent thrombosis

  During index patient hospitalization (at discharge from the hospital, up to 30 days)

• Timing of stent thrombosis

  During index patient hospitalization (at discharge from the hospital, up to 30 days)

• Survival

  During index hospitalization (at discharge from the hospital, up to 90 days)

• Survival (CPC)

  During index hospitalization (at discharge from the hospital, up to 90 days)

Study Arms (2)

Cangrelor + Ticagrelor

EXPERIMENTAL

Bolus of cangrelor (30 mcg/kg) and immediately afterwards a continuous intravenous infusion of 4 mcg/kg/min at the start of the primary percutaneous coronary intervention. Crushed and dissolved ticagrelor tablets (180 mg) will be given via inserted enteral tube.

Drug: Cangrelor 50 MG

Ticagrelor

NO INTERVENTION

Crushed and dissolved ticagrelor tablets (180 mg) will be given via enteral tube (standard care).

Interventions

Cangrelor 50 MG DRUG

30 mcg/kg bolus, then 4h infusion 4 mcg/kg/min

Also known as: Kengrexal 50 mg

Cangrelor + Ticagrelor

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age 18 to 70 years
• comatose survivors of out-of-hospital cardiac arrest undergoing primary percutaneous coronary intervention
• treatment with induced therapeutic hypothermia
• no contraindication for dual antiplatelet therapy

You may not qualify if:

• pregnancy
• patients without return of spontaneous circulation or patients on ECMO
• history of recent P2Y12 use (last 7 days)
• history of recent vitamin K antagonist or NOAC use (last 14 days)
• active bleeding
• history of transient ischemic attack or cerebral vascular insult
• strong bleeding tendency (Child C liver cirrhosis, stage IV-V chronic renal disease)
• history of allergic reactions to acetylsalicylic acid, heparin or P2Y12 inhibitors
• terminal disease or life expectancy less than 1 year

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead
• Chiesi Slovenija, d.o.o.: collaborator

Study Sites (1)

University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

Location

Related Publications (8)

• Radsel P, Knafelj R, Kocjancic S, Noc M. Angiographic characteristics of coronary disease and postresuscitation electrocardiograms in patients with aborted cardiac arrest outside a hospital. Am J Cardiol. 2011 Sep 1;108(5):634-8. doi: 10.1016/j.amjcard.2011.04.008. Epub 2011 Jun 14.

  PMID: 21676367 BACKGROUND

• Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimsky P; ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018 Jan 7;39(2):119-177. doi: 10.1093/eurheartj/ehx393. No abstract available.

  PMID: 28886621 BACKGROUND

• Hogberg C, Erlinge D, Braun OO. Mild hypothermia does not attenuate platelet aggregation and may even increase ADP-stimulated platelet aggregation after clopidogrel treatment. Thromb J. 2009 Feb 23;7:2. doi: 10.1186/1477-9560-7-2.

  PMID: 19236702 BACKGROUND

• Steblovnik K, Blinc A, Mijovski MB, Fister M, Mikuz U, Noc M. Ticagrelor Versus Clopidogrel in Comatose Survivors of Out-of-Hospital Cardiac Arrest Undergoing Percutaneous Coronary Intervention and Hypothermia: A Randomized Study. Circulation. 2016 Dec 20;134(25):2128-2130. doi: 10.1161/CIRCULATIONAHA.116.024872. No abstract available.

  PMID: 27994027 BACKGROUND

• Llitjos JF, Sideris G, Voicu S, Bal Dit Sollier C, Deye N, Megarbane B, Drouet L, Henry P, Dillinger JG. Impaired biological response to aspirin in therapeutic hypothermia comatose patients resuscitated from out-of-hospital cardiac arrest. Resuscitation. 2016 Aug;105:16-21. doi: 10.1016/j.resuscitation.2016.04.027. Epub 2016 May 17.

  PMID: 27224446 BACKGROUND

• Pruller F, Bis L, Milke OL, Fruhwald F, Patzold S, Altmanninger-Sock S, Siller-Matula J, von Lewinski F, Ablasser K, Sacherer M, von Lewinski D. Cangrelor Induces More Potent Platelet Inhibition without Increasing Bleeding in Resuscitated Patients. J Clin Med. 2018 Nov 15;7(11):442. doi: 10.3390/jcm7110442.

  PMID: 30445678 BACKGROUND

• Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449. No abstract available.

  PMID: 21670242 BACKGROUND

• Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG, Morel MA, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW; Academic Research Consortium. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007 May 1;115(17):2344-51. doi: 10.1161/CIRCULATIONAHA.106.685313.

  PMID: 17470709 BACKGROUND

MeSH Terms

Conditions

Out-of-Hospital Cardiac Arrest; Acute Coronary Syndrome

Interventions

cangrelor

Condition Hierarchy (Ancestors)

Heart Arrest; Heart Diseases; Cardiovascular Diseases; Myocardial Ischemia; Vascular Diseases

Study Officials

• Marko Noc, MD PhD

  University Medical Centre Ljubljana

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: April 1, 2019
• First Posted: July 2, 2019
• Study Start: July 1, 2019
• Primary Completion: November 27, 2021
• Study Completion: November 27, 2021
• Last Updated: December 3, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)