Cangrelor vs. Ticagrelor for Early Platelet Inhibition in STEMI

NCT03182855 | Unknown Phase 4 DMC

• 1 other identifier: 2016-003721-41
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, controlled trial compares the anti-thrombotic effect of cangrelor and ticagrelor on platelet activity in patients with acute ST-elevation myocardial infarction. Patients will receive either prehospital ticagrelor (180 mg - crushed) or in-hospital cangrelor (bolus 30 μg/kg within 1 minute followed by infusion (4 μg/kg/minute) for two hours) followed by 180 mg ticagrelor. The primary study end-point is platelet reactivity at sheath insertion, at the end of the PCI procedure (before sheath removal) and two hours after PCI is initiated. The secondary end-point is the proportion of patients with inappropriate or harmful P2Y12 administration.

Conditions

Acute Coronary Syndrome; Myocardial Infarction; STEMI - ST Elevation Myocardial Infarction

Keywords

Acute Coronary Syndrome; STEMI; Platelet reactivity; Anti-thrombotic therapy

Outcome Measures

Primary Outcomes (1)

• Platelet reactivity 10 minutes PCI after is initiated

  Platelet reactivity measured in platelet reactivity units (PRU) by the VerifyNow® assay 10 minutes after PCI is initiated.

  10 minutes

Secondary Outcomes (2)

• Platelet reactivity before and after PCI

  2 hours

• Proportion of patients with inappropriate or harmful P2Y12 administration

  4 hours

Study Arms (2)

Prehospital ticagrelor

ACTIVE COMPARATOR

Ticagrelor 180 mg orally administered in the ambulance as soon as possible after inclusion and before coronary angiography. The two pills are chewed and swallowed with a glass of water. In both groups heparin and bivalirudin will be administered as part of routine therapy. In hemodynamically compromised patients with a high thrombus load a glycoprotein IIb/IIIa inhibitor may be used as bail-out therapy (these patients will be excluded). These drugs are not deemed to be study medication.

Drug: Ticagrelor

Inhospital cangrelor tetrasodium

ACTIVE COMPARATOR

Ticagrelor 180 mg orally in combination with cangrelor intravenously (bolus 30 μg/kg within 1 minute followed by infusion (4 μg/kg/minute) for two hours) both administered immediately after coronary angiography, when PPCI is indicated. In both groups heparin and bivalirudin will be administered as part of routine therapy. In hemodynamically compromised patients with a high thrombus load a glycoprotein IIb/IIIa inhibitor may be used as bail-out therapy (these patients will be excluded). These drugs are not deemed to be study medication.

Drug: Ticagrelor; Drug: Cangrelor Tetrasodium

Interventions

Ticagrelor DRUG

ADP-receptor blocker. Oral formulation. Standard Therapy in Acute Myocardial Infarction. Administered in the ambulance in arm 1 and in the hospital (catheterization laboratory) in arm 2.

Also known as: Brilique, Brilinta

Inhospital cangrelor tetrasodium; Prehospital ticagrelor

Cangrelor Tetrasodium DRUG

Intravenous ADP-receptor blocker. Administered after hospital arrival in the catheterization laboratory.

Also known as: Kengrexal, Kengreal

Inhospital cangrelor tetrasodium

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients triaged for PPCI due to suspicion of STEMI.
• Symptom duration \< 12 hours

You may not qualify if:

• Already in treatment with ticagrelor, prasugrel or clopidogrel
• Treatment with oral anticoagulants (warfarin, coumarins, rivaroxaban, apixaban, dabigatran)
• Adjunctive use of glycoprotein IIb/IIIa inhibitor during PCI
• Active bleeding
• Known, severe kidney failure (GFR \< 30 ml/min) and/or liver disease
• Women of child bearing ability who are not using contraceptive medication
• Severe mental or psychiatric disease, altered mental state (including unconsciousness) making it impossible to achieve informed consent

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Related Publications (15)

• Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC); Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van 't Hof A, Widimsky P, Zahger D. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012 Oct;33(20):2569-619. doi: 10.1093/eurheartj/ehs215. Epub 2012 Aug 24. No abstract available.

  PMID: 22922416 BACKGROUND

• O'Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso JE, Tracy CM, Woo YJ, Zhao DX; CF/AHA Task Force. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Jan 29;127(4):529-55. doi: 10.1161/CIR.0b013e3182742c84. Epub 2012 Dec 17. No abstract available.

  PMID: 23247303 BACKGROUND

• Aradi D, Collet JP, Mair J, Plebani M, Merkely B, Jaffe AS, Mockel M, Giannitsis E, Thygesen K, ten Berg JM, Mueller C, Storey RF, Lindahl B, Huber K; Study Group on Biomarkers in Cardiology of the Acute Cardiovascular Care Association of the European Society of Cardiology; Working Group on Thrombosis of the European Society of Cardiology. Platelet function testing in acute cardiac care - is there a role for prediction or prevention of stent thrombosis and bleeding? Thromb Haemost. 2015 Feb;113(2):221-30. doi: 10.1160/TH14-05-0449. Epub 2014 Nov 20.

  PMID: 25413597 BACKGROUND

• Montalescot G, van 't Hof AW, Lapostolle F, Silvain J, Lassen JF, Bolognese L, Cantor WJ, Cequier A, Chettibi M, Goodman SG, Hammett CJ, Huber K, Janzon M, Merkely B, Storey RF, Zeymer U, Stibbe O, Ecollan P, Heutz WM, Swahn E, Collet JP, Willems FF, Baradat C, Licour M, Tsatsaris A, Vicaut E, Hamm CW; ATLANTIC Investigators. Prehospital ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med. 2014 Sep 11;371(11):1016-27. doi: 10.1056/NEJMoa1407024. Epub 2014 Sep 1.

  PMID: 25175921 RESULT

• Montalescot G, Bolognese L, Dudek D, Goldstein P, Hamm C, Tanguay JF, ten Berg JM, Miller DL, Costigan TM, Goedicke J, Silvain J, Angioli P, Legutko J, Niethammer M, Motovska Z, Jakubowski JA, Cayla G, Visconti LO, Vicaut E, Widimsky P; ACCOAST Investigators. Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes. N Engl J Med. 2013 Sep 12;369(11):999-1010. doi: 10.1056/NEJMoa1308075. Epub 2013 Sep 1.

  PMID: 23991622 RESULT

• Hansson EC, Dellborg M, Lepore V, Jeppsson A. Prevalence, indications and appropriateness of antiplatelet therapy in patients operated for acute aortic dissection: associations with bleeding complications and mortality. Heart. 2013 Jan;99(2):116-21. doi: 10.1136/heartjnl-2012-302717. Epub 2012 Oct 9.

  PMID: 23048167 RESULT

• Becker S, Chisholm G, Maeng M. Positive predictive value of clinically suspected ST-segment elevation myocardial infarction using angiographic verification. Am J Cardiol. 2013 Oct 1;112(7):923-7. doi: 10.1016/j.amjcard.2013.05.026. Epub 2013 Jun 14.

  PMID: 23768460 RESULT

• Angiolillo DJ, Firstenberg MS, Price MJ, Tummala PE, Hutyra M, Welsby IJ, Voeltz MD, Chandna H, Ramaiah C, Brtko M, Cannon L, Dyke C, Liu T, Montalescot G, Manoukian SV, Prats J, Topol EJ; BRIDGE Investigators. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA. 2012 Jan 18;307(3):265-74. doi: 10.1001/jama.2011.2002.

  PMID: 22253393 RESULT

• 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: 19923168 RESULT

• Bhatt DL, Lincoff AM, Gibson CM, Stone GW, McNulty S, Montalescot G, Kleiman NS, Goodman SG, White HD, Mahaffey KW, Pollack CV Jr, Manoukian SV, Widimsky P, Chew DP, Cura F, Manukov I, Tousek F, Jafar MZ, Arneja J, Skerjanec S, Harrington RA; CHAMPION PLATFORM Investigators. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med. 2009 Dec 10;361(24):2330-41. doi: 10.1056/NEJMoa0908629.

  PMID: 19915222 RESULT

• Harrington RA, Stone GW, McNulty S, White HD, Lincoff AM, Gibson CM, Pollack CV Jr, Montalescot G, Mahaffey KW, Kleiman NS, Goodman SG, Amine M, Angiolillo DJ, Becker RC, Chew DP, French WJ, Leisch F, Parikh KH, Skerjanec S, Bhatt DL. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med. 2009 Dec 10;361(24):2318-29. doi: 10.1056/NEJMoa0908628.

  PMID: 19915221 RESULT

• Bhatt DL, Stone GW, Mahaffey KW, Gibson CM, Steg PG, Hamm CW, Price MJ, Leonardi S, Gallup D, Bramucci E, Radke PW, Widimsky P, Tousek F, Tauth J, Spriggs D, McLaurin BT, Angiolillo DJ, Genereux P, Liu T, Prats J, Todd M, Skerjanec S, White HD, Harrington RA; CHAMPION PHOENIX Investigators. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013 Apr 4;368(14):1303-13. doi: 10.1056/NEJMoa1300815. Epub 2013 Mar 10.

  PMID: 23473369 RESULT

• Parodi G, Xanthopoulou I, Bellandi B, Gkizas V, Valenti R, Karanikas S, Migliorini A, Angelidis C, Abbate R, Patsilinakos S, Baldereschi GJ, Marcucci R, Gensini GF, Antoniucci D, Alexopoulos D. Ticagrelor crushed tablets administration in STEMI patients: the MOJITO study. J Am Coll Cardiol. 2015 Feb 10;65(5):511-2. doi: 10.1016/j.jacc.2014.08.056. No abstract available.

  PMID: 25660931 RESULT

• Parodi G, Valenti R, Bellandi B, Migliorini A, Marcucci R, Comito V, Carrabba N, Santini A, Gensini GF, Abbate R, Antoniucci D. Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID (Rapid Activity of Platelet Inhibitor Drugs) primary PCI study. J Am Coll Cardiol. 2013 Apr 16;61(15):1601-6. doi: 10.1016/j.jacc.2013.01.024. Epub 2013 Mar 22.

  PMID: 23500251 RESULT

• Alexopoulos D, Xanthopoulou I, Mavronasiou E, Stavrou K, Siapika A, Tsoni E, Davlouros P. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with diabetes. Diabetes Care. 2013 Aug;36(8):2211-6. doi: 10.2337/dc12-2510. Epub 2013 Mar 14.

  PMID: 23491524 RESULT

MeSH Terms

Conditions

Acute Coronary Syndrome; Myocardial Infarction; ST Elevation Myocardial Infarction

Interventions

Ticagrelor; cangrelor

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Jacob T Sorensen, MD, PhD

  Aarhus University Hospital, Department of Cardiology, Skejby

  PRINCIPAL INVESTIGATOR

• Steen D Kristensen, MD, DMSc

  Aarhus University Hospital, Department of Cardiology, Skejby

  STUDY DIRECTOR

Central Study Contacts

Jacob T Sorensen, MD, PhD

CONTACT

+4540143563; jacsoe@rm.dk

Steen D Kristensen, MD, DMSc

CONTACT

+4530922336; steendk@dadlnet.dk

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: Md, PhD

Model Details: Randomized trial. No blinding

Study Record Dates

• First Submitted: June 7, 2017
• First Posted: June 9, 2017
• Study Start: September 1, 2018
• Primary Completion: June 1, 2019
• Study Completion: August 1, 2019
• Last Updated: June 28, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)