NCT02224274

Brief 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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
57

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Aug 2014

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2014

Completed
18 days until next milestone

First Submitted

Initial submission to the registry

August 19, 2014

Completed
6 days until next milestone

First Posted

Study publicly available on registry

August 25, 2014

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2016

Completed
2.7 years until next milestone

Results Posted

Study results publicly available

February 27, 2019

Completed
Last Updated

February 27, 2019

Status Verified

October 1, 2018

Enrollment Period

1.8 years

First QC Date

August 19, 2014

Results QC Date

January 23, 2017

Last Update Submit

October 17, 2018

Conditions

Cardiac ArrestPostresuscitation SyndromeMyocardial Infarction (ST-Elevation Myocardial Infarction and Non-ST-Elevation Myocardial Infarction)

Keywords

Antiplatelet TherapyCardiac ArrestTherapeutic hypothermiaMyocardial infarction (ST-Elevation Myocardial Infarction and Non-ST-Elevation Myocardial Infarction)

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (2)

  • VerifyNow P2Y12Test - % Inhibition

    12 hours after P2Y12 inhibitor loading

  • Multiplate ADP Test

    12 hours after P2Y12 inhibitor loading

Study Arms (2)

Clopidogrel

ACTIVE COMPARATOR

These patients will be treated with clopidogrel 600 mg loading and than 75 mg/24 h.

Drug: Clopidogrel

Ticagrelor

EXPERIMENTAL

These patients will be treated with ticagrelor 180 mg loading and than 90 mg/12 h.

Drug: Ticagrelor

Interventions

ClopidogrelDRUG
Also known as: Clopidogrel (Plavix)
Clopidogrel
TicagrelorDRUG
Also known as: Ticagrelor (Brilique)
Ticagrelor

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

Location

Related Publications (9)

  • 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.

    PMID: 24800722BACKGROUND

  • 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.

    PMID: 23890998BACKGROUND

  • 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.

    PMID: 19923168BACKGROUND

  • 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. doi: 10.1016/j.resuscitation.2006.07.013. Epub 2006 Dec 11.

    PMID: 17161902BACKGROUND

  • 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. doi: 10.1056/NEJMoa003289.

    PMID: 11856794BACKGROUND

  • 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. No abstract available.

    PMID: 23591428BACKGROUND

  • Souckova L, Opatrilova R, Suk P, Cundrle I Jr, Pavlik M, Zvonicek V, Hlinomaz O, Sramek 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.

    PMID: 22890586BACKGROUND

  • Bjelland TW, Hjertner O, 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.

    PMID: 20727659BACKGROUND

  • 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.

    PMID: 19535947BACKGROUND

MeSH Terms

Conditions

Heart ArrestNon-ST Elevated Myocardial Infarction

Interventions

ClopidogrelTicagrelor

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesMyocardial InfarctionMyocardial IschemiaVascular DiseasesInfarctionIschemiaPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosis

Intervention Hierarchy (Ancestors)

TiclopidineThienopyridinesThiophenesSulfur CompoundsOrganic ChemicalsPyridinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingAdenosinePurine NucleosidesPurinesNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosides

Limitations and Caveats

Did not address effectiveness of prasugrel. Not powered to address stent thrombosis or bleeding.

Results Point of Contact

Title
Marko Noc
Organization
UMC Ljubljana
marko.noc@mf.uni-lj.si
+386 1 522 22 96

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Marko Noc, MD, PhD

Study Record Dates

First Submitted

August 19, 2014

First Posted

August 25, 2014

Study Start

August 1, 2014

Primary Completion

June 1, 2016

Study Completion

June 1, 2016

Last Updated

February 27, 2019

Results First Posted

February 27, 2019

Record last verified: 2018-10

Locations

SL(1)