Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome

NCT ID: NCT01944800

Last Updated: 2023-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 4018 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-15
• Study Completion Date: 2021-09-30

Brief Summary

Aim of the randomized, open-label, multicenter ISAR-REACT 5 trial is to assess whether ticagrelor is superior to prasugrel in patients with acute coronary syndrome and planned invasive strategy in terms of clinical outcomes.

Conditions

Acute Coronary Syndrome (ACS)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Ticagrelor

Group Type: EXPERIMENTAL

Ticagrelor

Intervention Type: DRUG

Loading dose of 180 mg, followed by maintenance dose of 180 mg per day

Prasugrel

Group Type: ACTIVE_COMPARATOR

Prasugrel

Intervention Type: DRUG

Loading dose of 60 mg, followed by maintenance dose of 10 mg/day or 5 mg/day in patients =/\> 75 years or \< 60 kg

Interventions

Ticagrelor

Loading dose of 180 mg, followed by maintenance dose of 180 mg per day

Intervention Type: DRUG

Prasugrel

Loading dose of 60 mg, followed by maintenance dose of 10 mg/day or 5 mg/day in patients =/\> 75 years or \< 60 kg

Intervention Type: DRUG

Other Intervention Names

Brilique; Efient

Eligibility Criteria

Inclusion Criteria

Hospitalization for an acute coronary syndrome (ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction or unstable angina pectoris) with planned invasive strategy

Exclusion Criteria

1. intolerance of or allergy to ticagrelor or prasugrel

2. history of any stroke, transient ischemic attack or intracranial bleeding

3. known intracranial neoplasm, intracranial arteriovenous malformation or intracranial aneurysm

4. active bleeding, clinical findings, that in the judgement of the investigator are associated with an increased risk of bleeding

5. fibrin-specific fibrinolytic therapy less than 24 h before randomization, non-fibrin-specific fibrinolytic therapy less than 48 h before randomization

6. known platelet count < 100.000/μL at the time of screening

7. known anemia (hemoglobin <10 g/dL) at the time of screening

8. oral anticoagulation that cannot be safely discontinued for the duration of the study

9. INR known to be greater than 1.5 at the time of screening

10. chronic renal insufficiency requiring dialysis

11. moderate or severe hepatic dysfunction (Child Pugh B or C)

12. increased risk of bradycardia events (Sick Sinus, AV block grade II or III, bradycardia-induced syncope)

13. index event is an acute complication (< 30 days) of PCI

14. concomitant medical illness that in the opinion of the investigator is associated with a life expectancy < 1 year

15. concomitant oral or i.v. therapy with strong CYP3A Inhibitors (e.g. ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, grapefruit juice > 1 L/d), CYP3A substrates with narrow therapeutic indices (e.g. cyclosporine, quinidine), or strong CYP3A inducers (e.g. rifampin/rifampicin, phenytoin, carbamazepine, dexamethason, phenobarbital ) that cannot be safely discontinued

16. ≥1 doses of ticagrelor or prasugrel within 5 days before randomisation

17. no written informed consent

18. participation in another investigational drug study

19. previous enrolment in this study

20. for women of childbearing potential no negative pregnancy test and no agree to use reliable method of birth control during the study

21. Pregnancy, giving birth within the last 90 days, or lactation

22. inability to cooperate with protocol requirements

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)

OTHER

Sponsor Role: collaborator

Deutsches Herzzentrum Muenchen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adnan Kastrati, MD

Role: STUDY_CHAIR

Deutsches Herzzentrum München

Stefanie Schuepke, MD

Role: PRINCIPAL_INVESTIGATOR

Deutsches Herzzentrum München

Locations

Universitäts-Herzzentrum Freiburg/ Bad Krozingen

Bad Krozingen, Baden-Wurttemberg, Germany

Universitäts-Klinikum Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Universitätsklinikum Mannheim

Mannheim, Baden-Wurttemberg, Germany

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Klinikum Landkreis Erding

Erding, Bavaria, Germany

Deutsches Herzzentrum Munich

München, Bavaria, Germany

Klinikum rechts der Isar, 1. Medizinische Klinik und Poliklinik

München, Bavaria, Germany

Klinikum Neuperlach

München, Bavaria, Germany

Universitätsklinikum Regensburg

Regensburg, Bavaria, Germany

Klinikum Traunstein

Traunstein, Bavaria, Germany

Kerckhoff-Klinik GmbH, Abteilung für Kardiologie

Bad Nauheim, Hesse, Germany

Universitätsmedizin Göttingen, Herzzentrum

Göttingen, Lower Saxony, Germany

Herzzentrum Wuppertal

Wuppertal, North Rhine-Westphalia, Germany

Segeberger Kliniken GmbH

Bad Segeberg, Schleswig-Holstein, Germany

Universitätsklinikum Schleswig-Holstein, Klinik für Innere Medizin III, Campus Kiel

Kiel, Schleswig-Holstein, Germany

Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin

Berlin, , Germany

Charité Universitätsmedizin Berlin, Campus Virchow-Klinik

Berlin, , Germany

Careggi University Hospital, Invasive Cardiology Division

Florence, , Italy

Spaziani Hospital Frosinone

Frosinone, , Italy

Countries

Germany; Italy

References

Bongiovanni D, Schreiner N, Gosetti R, Mayer K, Angiolillo DJ, Sibbing D, Holdenrieder S, Anetsberger A, von Scheidt M, Schunkert H, Laugwitz KL, Schupke S, Kastrati A, Fegers-Wustrow I, Bernlochner I. Immature Platelet Fraction Predicts Adverse Events in Patients With Acute Coronary Syndrome: the ISAR-REACT 5 Reticulated Platelet Substudy. Arterioscler Thromb Vasc Biol. 2023 Feb;43(2):e83-e93. doi: 10.1161/ATVBAHA.122.318614. Epub 2022 Dec 22.

Reference Type: DERIVED

PMID: 36546322 (View on PubMed)

Lahu S, Scalamogna M, Ndrepepa G, Menichelli M, Valina C, Hemetsberger R, Witzenbichler B, Bernlochner I, Joner M, Xhepa E, Hapfelmeier A, Kufner S, Sager HB, Mayer K, Kessler T, Laugwitz KL, Richardt G, Schunkert H, Neumann FJ, Kastrati A, Cassese S. Prior Myocardial Infarction and Treatment Effect of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndromes - A Post-hoc Analysis of the ISAR-REACT 5 Trial. J Am Heart Assoc. 2022 Dec 20;11(24):e027257. doi: 10.1161/JAHA.122.027257. Epub 2022 Dec 14.

Reference Type: DERIVED

PMID: 36515247 (View on PubMed)

Aytekin A, Coughlan JJ, Ndrepepa G, Cassese S, Lahu S, Kufner S, Mayer K, Xhepa E, Gewalt S, Joner M, Hapfelmeier A, Angiolillo DJ, Menichelli M, Richardt G, Neumann FJ, Schunkert H, Kastrati A. The effect of a Prasugrel- vs. a Ticagrelor-based strategy on total ischaemic and bleeding events in patients with acute coronary syndromes. Eur Heart J Cardiovasc Pharmacother. 2023 Apr 10;9(3):231-239. doi: 10.1093/ehjcvp/pvac067.

Reference Type: DERIVED

PMID: 36434779 (View on PubMed)

Lahu S, Presch A, Ndrepepa G, Menichelli M, Valina C, Hemetsberger R, Witzenbichler B, Bernlochner I, Joner M, Xhepa E, Hapfelmeier A, Kufner S, Rifatov N, Sager HB, Mayer K, Kessler T, Laugwitz KL, Richardt G, Schunkert H, Neumann FJ, Sibbing D, Angiolillo DJ, Kastrati A, Cassese S. Ticagrelor or Prasugrel in Patients With Acute Coronary Syndrome and High Bleeding Risk. Circ Cardiovasc Interv. 2022 Oct;15(10):e012204. doi: 10.1161/CIRCINTERVENTIONS.122.012204. Epub 2022 Oct 18.

Reference Type: DERIVED

PMID: 36256695 (View on PubMed)

Behnes M, Lahu S, Ndrepepa G, Menichelli M, Mayer K, Wohrle J, Bernlochner I, Gewalt S, Witzenbichler B, Hochholzer W, Sibbing D, Cassese S, Angiolillo DJ, Hemetsberger R, Valina C, Muller A, Kufner S, Hamm CW, Xhepa E, Hapfelmeier A, Sager HB, Joner M, Fusaro M, Richardt G, Laugwitz KL, Neumann FJ, Schunkert H, Schupke S, Kastrati A, Akin I. Ticagrelor or prasugrel in patients with acute coronary syndrome with off-hour versus on-hour presentation: a subgroup analysis of the ISAR-REACT 5 trial. Clin Res Cardiol. 2023 Apr;112(4):518-528. doi: 10.1007/s00392-022-02040-z. Epub 2022 Jul 5.

Reference Type: DERIVED

PMID: 35789430 (View on PubMed)

Hemetsberger R, Richardt G, Lahu S, Valina C, Menichelli M, Abdelghani M, Wohrle J, Toelg R, Witzenbichler B, Mankerious N, Liebetrau C, Bernlochner I, Hamm CW, Allali A, Joner M, Fusaro M, Xhepa E, Hapfelmeier A, Kufner S, Sager HB, Schupke S, Laugwitz KL, Schunkert H, Neumann FJ, Kastrati A, Cassese S. Access Route and Clinical Outcomes After Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome Undergoing Invasive Treatment Strategy. Cardiovasc Revasc Med. 2022 Aug;41:122-128. doi: 10.1016/j.carrev.2021.12.029. Epub 2022 Jan 3.

Reference Type: DERIVED

PMID: 35045943 (View on PubMed)

Lahu S, Behnes M, Ndrepepa G, Neumann FJ, Sibbing D, Bernlochner I, Menichelli M, Mayer K, Richardt G, Gewalt S, Angiolillo DJ, Coughlan JJ, Aytekin A, Witzenbichler B, Hochholzer W, Cassese S, Kufner S, Xhepa E, Sager HB, Joner M, Fusaro M, Laugwitz KL, Schunkert H, Schupke S, Kastrati A, Akin I. Body mass index and efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndromes. Rev Esp Cardiol (Engl Ed). 2022 Sep;75(9):747-755. doi: 10.1016/j.rec.2021.11.007. Epub 2021 Dec 24. English, Spanish.

Reference Type: DERIVED

PMID: 34961732 (View on PubMed)

Ndrepepa G, Neumann FJ, Menichelli M, Bernlochner I, Richardt G, Wohrle J, Witzenbichler B, Mayer K, Cassese S, Gewalt S, Xhepa E, Kufner S, Sager HB, Joner M, Ibrahim T, Laugwitz KL, Schunkert H, Schupke S, Kastrati A. Assessment of Impact of Patient Recruitment Volume on Risk Profile, Outcomes, and Treatment Effect in a Randomized Trial of Ticagrelor Versus Prasugrel in Acute Coronary Syndromes. J Am Heart Assoc. 2021 Nov 16;10(22):e021418. doi: 10.1161/JAHA.121.021418. Epub 2021 Nov 15.

Reference Type: DERIVED

PMID: 34779234 (View on PubMed)

Ndrepepa G, Holdenrieder S, Neumann FJ, Lahu S, Cassese S, Joner M, Xhepa E, Kufner S, Wiebe J, Laugwitz KL, Gewalt S, Schunkert H, Kastrati A. Prognostic value of glomerular function estimated by Cockcroft-Gault creatinine clearance, MDRD-4, CKD-EPI and European Kidney Function Consortium equations in patients with acute coronary syndromes. Clin Chim Acta. 2021 Dec;523:106-113. doi: 10.1016/j.cca.2021.09.007. Epub 2021 Sep 13.

Reference Type: DERIVED

PMID: 34529983 (View on PubMed)

Coughlan JJ, Aytekin A, Ndrepepa G, Schupke S, Bernlochner I, Mayer K, Neumann FJ, Menichelli M, Richardt G, Wohrle J, Xhepa E, Kufner S, Sager HB, Joner M, Ibrahim T, Fusaro M, Laugwitz KL, Schunkert H, Kastrati A, Cassese S. Twelve-month clinical outcomes in patients with acute coronary syndrome undergoing complex percutaneous coronary intervention: insights from the ISAR-REACT 5 trial. Eur Heart J Acute Cardiovasc Care. 2021 Dec 18;10(10):1117-1124. doi: 10.1093/ehjacc/zuab077.

Reference Type: DERIVED

PMID: 34468709 (View on PubMed)

Wohrle J, Seeger J, Lahu S, Mayer K, Bernlochner I, Gewalt S, Menichelli M, Witzenbichler B, Hochholzer W, Sibbing D, Cassese S, Angiolillo DJ, Hemetsberger R, Valina C, Kufner S, Xhepa E, Hapfelmeier A, Sager HB, Joner M, Richardt G, Laugwitz KL, Neumann FJ, Schunkert H, Schupke S, Kastrati A, Ndrepepa G. Ticagrelor or Prasugrel in Patients With Acute Coronary Syndrome in Relation to Estimated Glomerular Filtration Rate. JACC Cardiovasc Interv. 2021 Sep 13;14(17):1857-1866. doi: 10.1016/j.jcin.2021.06.028. Epub 2021 Aug 23.

Reference Type: DERIVED

PMID: 34446390 (View on PubMed)

Coughlan JJ, Aytekin A, Lahu S, Ndrepepa G, Menichelli M, Mayer K, Wohrle J, Bernlochner I, Gewalt S, Witzenbichler B, Hochholzer W, Sibbing D, Cassese S, Angiolillo DJ, Hemetsberger R, Valina C, Muller A, Kufner S, Liebetrau C, Xhepa E, Hapfelmeier A, Sager HB, Joner M, Fusaro M, Richardt G, Laugwitz KL, Neumann FJ, Schunkert H, Schupke S, Kastrati A. Ticagrelor or Prasugrel for Patients With Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention: A Prespecified Subgroup Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2021 Oct 1;6(10):1121-1129. doi: 10.1001/jamacardio.2021.2228.

Reference Type: DERIVED

PMID: 34190967 (View on PubMed)

Coughlan JJ, Aytekin A, Ndrepepa G, Schupke S, Bernlochner I, Mayer K, Neumann FJ, Menichelli M, Richardt G, Wohrle J, Witzenbichler B, Gewalt S, Xhepa E, Kufner S, Sager HB, Joner M, Ibrahim T, Fusaro M, Laugwitz KL, Schunkert H, Kastrati A, Cassese S. Ticagrelor or Prasugrel in Patients With Acute Coronary Syndrome Undergoing Complex Percutaneous Coronary Intervention. Circ Cardiovasc Interv. 2021 Jul;14(7):e010565. doi: 10.1161/CIRCINTERVENTIONS.121.010565. Epub 2021 Jun 16.

Reference Type: DERIVED

PMID: 34130477 (View on PubMed)

Lahu S, Ndrepepa G, Gewalt S, Schupke S, Pellegrini C, Bernlochner I, Aytekin A, Neumann FJ, Menichelli M, Richardt G, Cassese S, Xhepa E, Kufner S, Sager HB, Joner M, Ibrahim T, Fusaro M, Laugwitz KL, Schunkert H, Kastrati A, Mayer K. Efficacy and safety of ticagrelor versus prasugrel in smokers and nonsmokers with acute coronary syndromes. Int J Cardiol. 2021 Sep 1;338:8-13. doi: 10.1016/j.ijcard.2021.06.011. Epub 2021 Jun 11.

Reference Type: DERIVED

PMID: 34126130 (View on PubMed)

Mayer K, Bongiovanni D, Karschin V, Sibbing D, Angiolillo DJ, Schunkert H, Laugwitz KL, Schupke S, Kastrati A, Bernlochner I. Ticagrelor or Prasugrel for Platelet Inhibition in Acute Coronary Syndrome Patients: The ISAR-REACT 5 Trial. J Am Coll Cardiol. 2020 Nov 24;76(21):2569-2571. doi: 10.1016/j.jacc.2020.09.586. No abstract available.

Reference Type: DERIVED

PMID: 33213734 (View on PubMed)

Valina C, Neumann FJ, Menichelli M, Mayer K, Wohrle J, Bernlochner I, Aytekin A, Richardt G, Witzenbichler B, Sibbing D, Cassese S, Angiolillo DJ, Kufner S, Liebetrau C, Hamm CW, Xhepa E, Hapfelmeier A, Sager HB, Wustrow I, Joner M, Trenk D, Laugwitz KL, Schunkert H, Schupke S, Kastrati A. Ticagrelor or Prasugrel in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes. J Am Coll Cardiol. 2020 Nov 24;76(21):2436-2446. doi: 10.1016/j.jacc.2020.09.584.

Reference Type: DERIVED

PMID: 33213722 (View on PubMed)

Aytekin A, Ndrepepa G, Neumann FJ, Menichelli M, Mayer K, Wohrle J, Bernlochner I, Lahu S, Richardt G, Witzenbichler B, Sibbing D, Cassese S, Angiolillo DJ, Valina C, Kufner S, Liebetrau C, Hamm CW, Xhepa E, Hapfelmeier A, Sager HB, Wustrow I, Joner M, Trenk D, Fusaro M, Laugwitz KL, Schunkert H, Schupke S, Kastrati A. Ticagrelor or Prasugrel in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. Circulation. 2020 Dec 15;142(24):2329-2337. doi: 10.1161/CIRCULATIONAHA.120.050244. Epub 2020 Oct 29.

Reference Type: DERIVED

PMID: 33115278 (View on PubMed)

Ndrepepa G, Kastrati A, Menichelli M, Neumann FJ, Wohrle J, Bernlochner I, Richardt G, Witzenbichler B, Sibbing D, Gewalt S, Angiolillo DJ, Hamm CW, Hapfelmeier A, Trenk D, Laugwitz KL, Schunkert H, Schupke S, Mayer K. Ticagrelor or Prasugrel in Patients With Acute Coronary Syndromes and Diabetes Mellitus. JACC Cardiovasc Interv. 2020 Oct 12;13(19):2238-2247. doi: 10.1016/j.jcin.2020.07.032.

Reference Type: DERIVED

PMID: 33032712 (View on PubMed)

Menichelli M, Neumann FJ, Ndrepepa G, Mayer K, Wohrle J, Bernlochner I, Richardt G, Witzenbichler B, Sibbing D, Gewalt S, Angiolillo DJ, Lahu S, Hamm CW, Hapfelmeier A, Trenk D, Laugwitz KL, Schunkert H, Schupke S, Kastrati A. Age- and Weight-Adapted Dose of Prasugrel Versus Standard Dose of Ticagrelor in Patients With Acute Coronary Syndromes : Results From a Randomized Trial. Ann Intern Med. 2020 Sep 15;173(6):436-444. doi: 10.7326/M20-1806. Epub 2020 Jul 21.

Reference Type: DERIVED

PMID: 32687741 (View on PubMed)

Schupke S, Neumann FJ, Menichelli M, Mayer K, Bernlochner I, Wohrle J, Richardt G, Liebetrau C, Witzenbichler B, Antoniucci D, Akin I, Bott-Flugel L, Fischer M, Landmesser U, Katus HA, Sibbing D, Seyfarth M, Janisch M, Boncompagni D, Hilz R, Rottbauer W, Okrojek R, Mollmann H, Hochholzer W, Migliorini A, Cassese S, Mollo P, Xhepa E, Kufner S, Strehle A, Leggewie S, Allali A, Ndrepepa G, Schuhlen H, Angiolillo DJ, Hamm CW, Hapfelmeier A, Tolg R, Trenk D, Schunkert H, Laugwitz KL, Kastrati A; ISAR-REACT 5 Trial Investigators. Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes. N Engl J Med. 2019 Oct 17;381(16):1524-1534. doi: 10.1056/NEJMoa1908973. Epub 2019 Sep 1.

Reference Type: DERIVED

PMID: 31475799 (View on PubMed)

Schulz S, Angiolillo DJ, Antoniucci D, Bernlochner I, Hamm C, Jaitner J, Laugwitz KL, Mayer K, von Merzljak B, Morath T, Neumann FJ, Richardt G, Ruf J, Schomig G, Schuhlen H, Schunkert H, Kastrati A; Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 5 Trial Investigators. Randomized comparison of ticagrelor versus prasugrel in patients with acute coronary syndrome and planned invasive strategy--design and rationale of the iNtracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 5 trial. J Cardiovasc Transl Res. 2014 Feb;7(1):91-100. doi: 10.1007/s12265-013-9527-3. Epub 2013 Dec 27.

Reference Type: DERIVED

PMID: 24371012 (View on PubMed)

Other Identifiers

2013-002272-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GE IDE 00113

Identifier Type: -

Identifier Source: org_study_id