Antiplatelet Therapy After Cardiac Arrest

Cardiac Arrest Clinical Trial

Official title:

Comparison of Antiplatelet Therapy With Clopidogrel and Ticagrelor in Patients After Cardiac Arrest Treated With Therapeutic Hypothermia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02224274
• Other study ID #: Hypothermia: Clopi vs Tica
• Status: Completed
• Phase: Phase 4
• Start date: August 2014
• Est. completion date: June 2016

Study information

• Verified date: October 2018
• Source: University Medical Centre Ljubljana
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

There is growing evidence that standard dual antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel is not as effective in the setting of therapeutic hypothermia after cardiac arrest as in normothermic patients. The reasons for this are probably slower gastrointestinal motility, absorption and liver metabolism required for clopidogrel to take action. Since ticagrelor has faster intestinal absorption and no need for liver metabolism we expect its effect to be good even in patients with therapeutic hypothermia after cardiac arrest. Patients treated with therapeutic hypothermia after cardiac arrest and percutaneous coronary intervention will be randomised into two groups. One will be treated with ASA and clopidogrel and the other with ASA and ticagrelor. Blood samples will be collected before and 2, 4, 12, 22 and 48 hours after P2Y12 inhibitor administration. Platelet function will be measured by VerifyNow P2Y12 assay and by Multiplate ADPTest. Differences between the groups will be analysed.

Hypothesis: Antiplatelet therapy with ticagrelor is more effective than therapy with clopidogrel in the comatose survivors of cardiac arrest treated with therapeutic hypothermia and percutaneous coronary intervention (PCI).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Female and male over 18 years old

• Unconscious survivors of cardiac arrest treated with therapeutic hypothermia

• Acute coronary syndrome (NSTEMI or STEMI) as a reason of cardiac arrest

• PCI with stent implantation

• Provision of informed consent prior to any study specific procedures is impossible because subjects are unconscious at the moment of inclusion

Exclusion Criteria:

• Use of any P2Y12 inhibitors in last 10 days

• Use of prasugrel before and 48 hours after loading dose of P2Y12 inhibitor

• Use of eptifibatide before and 48 hours after loading dose of P2Y12 inhibitor

• Thrombocytopenia (<50*109/L)

• Allergic reaction to acetylsalicylic acid, clopidogrel or ticagrelor

• Ticagrelor contraindications: previous intracranial bleeding, active pathological bleeding, moderate to severe hepatic impairment, heart rate < 40/min at presentation

• Suspected or confirmed pregnancy

• Use of bivalirudin before and 48 hours after loading dose of P2Y12 inhibitor

Related Conditions & MeSH terms

• Cardiac Arrest
• Heart Arrest
• Infarction
• Myocardial Infarction
• Myocardial Infarction (ST-Elevation Myocardial Infarction and Non-ST-Elevation Myocardial Infarction)
• Non-ST Elevated Myocardial Infarction
• Postresuscitation Syndrome
• ST Elevation Myocardial Infarction

Intervention

Drug:
• Clopidogrel

• Ticagrelor

Locations

Country	Name	City	State
Slovenia	University Medical Centre Ljubljana	Ljubljana

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Centre Ljubljana

Country where clinical trial is conducted

Slovenia, 

References & Publications (9)

Alexopoulos D, Xanthopoulou I, Gkizas V, Kassimis G, Theodoropoulos K, Makris G, Koutsogiannis N, Damelou A, Tsigkas G, Davlouros P, Hahalis G. Response to letter regarding article, "Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST-segment-elevation myocardial infarction". Circ Cardiovasc Interv. 2013 Apr;6(2):e29. doi: 10.1161/CIRCINTERVENTIONS.113.000134. — View Citation

Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002 Feb 21;346(8):557-63. — View Citation

Bjelland TW, Hjertner Ø, Klepstad P, Kaisen K, Dale O, Haugen BO. Antiplatelet effect of clopidogrel is reduced in patients treated with therapeutic hypothermia after cardiac arrest. Resuscitation. 2010 Dec;81(12):1627-31. doi: 10.1016/j.resuscitation.2010.07.002. Epub 2010 Aug 19. — View Citation

Gorjup V, Radsel P, Kocjancic ST, Erzen D, Noc M. Acute ST-elevation myocardial infarction after successful cardiopulmonary resuscitation. Resuscitation. 2007 Mar;72(3):379-85. Epub 2006 Dec 11. — View Citation

Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C, Teng R, Antonino MJ, Patil SB, Karunakaran A, Kereiakes DJ, Parris C, Purdy D, Wilson V, Ledley GS, Storey RF. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009 Dec 22;120(25):2577-85. doi: 10.1161/CIRCULATIONAHA.109.912550. Epub 2009 Nov 18. — View Citation

Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med. 2009 Jul;37(7 Suppl):S186-202. doi: 10.1097/CCM.0b013e3181aa5241. Review. — View Citation

Soucková L, Opatrilová R, Suk P, Cundrle I Jr, Pavlík M, Zvonícek V, Hlinomaz O, Šrámek V. Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR). Eur J Clin Pharmacol. 2013 Mar;69(3):309-17. doi: 10.1007/s00228-012-1360-0. Epub 2012 Aug 14. — View Citation

Steblovnik K, Blinc A, Bozic-Mijovski M, Kranjec I, Melkic E, Noc M. Platelet reactivity in comatose survivors of cardiac arrest undergoing percutaneous coronary intervention and hypothermia. EuroIntervention. 2015 Apr;10(12):1418-24. doi: 10.4244/EIJY14M05_02. — View Citation

Stone GW, Witzenbichler B, Weisz G, Rinaldi MJ, Neumann FJ, Metzger DC, Henry TD, Cox DA, Duffy PL, Mazzaferri E, Gurbel PA, Xu K, Parise H, Kirtane AJ, Brodie BR, Mehran R, Stuckey TD; ADAPT-DES Investigators. Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet. 2013 Aug 17;382(9892):614-23. doi: 10.1016/S0140-6736(13)61170-8. Epub 2013 Jul 26. Erratum in: Lancet. 2014 Mar 29;383(9923):1128. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	VerifyNow P2Y12Test - Platelet Reactivity	Platelet reactivity reflects P2Y12 inhibitor effect. Higher values mean normal platelet reactivity due to low P2Y12 inhibition response, while lower values mean decreased platelet reactivity due to the effect of a P2Y12 inhibitor. High on-treatment platelet reactivity was defined as >208 PRU.	12 h after P2Y12 inhibitor loading
Secondary	VerifyNow P2Y12Test - % Inhibition	% inhibition reflects P2Y12 inhibitor effect regarding basal platelet reactivity (defined as: (1- (platelet reactivity/basal platelet reactivity)) x 100). Higher values mean better P2Y12 inhibition response. High on-treatment platelet reactivity was defined as <11% inhibition.	12 hours after P2Y12 inhibitor loading
Secondary	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.	12 hours after P2Y12 inhibitor loading