NCT01944800

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.

Trial Health

90
On Track

Trial Health Score

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

Enrollment
4,018

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Sep 2013

Longer than P75 for phase_4

Geographic Reach
2 countries

19 active sites

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

First Submitted

Initial submission to the registry

September 13, 2013

Completed
2 days until next milestone

Study Start

First participant enrolled

September 15, 2013

Completed
3 days until next milestone

First Posted

Study publicly available on registry

September 18, 2013

Completed
5.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2019

Completed
2.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2021

Completed
Last Updated

February 6, 2023

Status Verified

February 1, 2023

Enrollment Period

5.8 years

First QC Date

September 13, 2013

Last Update Submit

February 3, 2023

Conditions

Acute Coronary Syndrome (ACS)

Keywords

TicagrelorPrasugrelAcute coronary syndromePercutaneous coronary intervention

Outcome Measures

Primary Outcomes (1)

  • Composite of death, myocardial infarction or stroke

    12 months

Secondary Outcomes (5)

  • Bleeding

    12 months

  • Mortality

    12 months

  • Stroke

    12 months

  • Myocardial Infarction

    12 months

  • Stent Thrombosis

    12 months

Study Arms (2)

Ticagrelor

EXPERIMENTAL
Drug: Ticagrelor

Prasugrel

ACTIVE COMPARATOR
Drug: Prasugrel

Interventions

TicagrelorDRUG

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

Also known as: Brilique
Ticagrelor
PrasugrelDRUG

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

Also known as: Efient
Prasugrel

Eligibility Criteria

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

You may qualify if:

  • 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

You may not qualify if:

  • intolerance of or allergy to ticagrelor or prasugrel
  • history of any stroke, transient ischemic attack or intracranial bleeding
  • known intracranial neoplasm, intracranial arteriovenous malformation or intracranial aneurysm
  • active bleeding, clinical findings, that in the judgement of the investigator are associated with an increased risk of bleeding
  • fibrin-specific fibrinolytic therapy less than 24 h before randomization, non-fibrin-specific fibrinolytic therapy less than 48 h before randomization
  • known platelet count \< 100.000/μL at the time of screening
  • known anemia (hemoglobin \<10 g/dL) at the time of screening
  • oral anticoagulation that cannot be safely discontinued for the duration of the study
  • INR known to be greater than 1.5 at the time of screening
  • chronic renal insufficiency requiring dialysis
  • moderate or severe hepatic dysfunction (Child Pugh B or C)
  • increased risk of bradycardia events (Sick Sinus, AV block grade II or III, bradycardia-induced syncope)
  • index event is an acute complication (\< 30 days) of PCI
  • concomitant medical illness that in the opinion of the investigator is associated with a life expectancy \< 1 year
  • 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
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (19)

Universitäts-Herzzentrum Freiburg/ Bad Krozingen

Bad Krozingen, Baden-Wurttemberg, 79189, Germany

Location

Universitäts-Klinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Universitätsklinikum Mannheim

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Klinikum Landkreis Erding

Erding, Bavaria, 85435, Germany

Location

Deutsches Herzzentrum Munich

München, Bavaria, 80636, Germany

Location

Klinikum rechts der Isar, 1. Medizinische Klinik und Poliklinik

München, Bavaria, 81675, Germany

Location

Klinikum Neuperlach

München, Bavaria, 81737, Germany

Location

Universitätsklinikum Regensburg

Regensburg, Bavaria, 93042, Germany

Location

Klinikum Traunstein

Traunstein, Bavaria, 83278, Germany

Location

Kerckhoff-Klinik GmbH, Abteilung für Kardiologie

Bad Nauheim, Hesse, 61231, Germany

Location

Universitätsmedizin Göttingen, Herzzentrum

Göttingen, Lower Saxony, 37099, Germany

Location

Herzzentrum Wuppertal

Wuppertal, North Rhine-Westphalia, 42117, Germany

Location

Segeberger Kliniken GmbH

Bad Segeberg, Schleswig-Holstein, 23795, Germany

Location

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

Kiel, Schleswig-Holstein, 24105, Germany

Location

Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin

Berlin, 12203, Germany

Location

Charité Universitätsmedizin Berlin, Campus Virchow-Klinik

Berlin, 13353, Germany

Location

Careggi University Hospital, Invasive Cardiology Division

Florence, 50141, Italy

Location

Spaziani Hospital Frosinone

Frosinone, 03100, Italy

Location

Related Publications (21)

  • 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.

    PMID: 36546322DERIVED

  • 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.

    PMID: 36515247DERIVED

  • 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.

    PMID: 36434779DERIVED

  • 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.

    PMID: 36256695DERIVED

  • 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.

    PMID: 35789430DERIVED

  • 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.

    PMID: 35045943DERIVED

  • 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.

    PMID: 34961732DERIVED

  • 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.

    PMID: 34779234DERIVED

  • 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.

    PMID: 34529983DERIVED

  • 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.

    PMID: 34468709DERIVED

  • 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.

    PMID: 34446390DERIVED

  • 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.

    PMID: 34190967DERIVED

  • 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.

    PMID: 34130477DERIVED

  • 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.

    PMID: 34126130DERIVED

  • 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.

    PMID: 33213734DERIVED

  • 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.

    PMID: 33213722DERIVED

  • 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.

    PMID: 33115278DERIVED

  • 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.

    PMID: 33032712DERIVED

  • 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.

    PMID: 32687741DERIVED

  • 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.

    PMID: 31475799DERIVED

  • 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.

    PMID: 24371012DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

TicagrelorPrasugrel Hydrochloride

Condition Hierarchy (Ancestors)

Myocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular Diseases

Intervention Hierarchy (Ancestors)

AdenosinePurine NucleosidesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosidesThiophenesSulfur CompoundsOrganic ChemicalsPiperazinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Adnan Kastrati, MD

    Deutsches Herzzentrum München

    STUDY CHAIR

  • Stefanie Schuepke, MD

    Deutsches Herzzentrum München

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 13, 2013

First Posted

September 18, 2013

Study Start

September 15, 2013

Primary Completion

July 1, 2019

Study Completion

September 1, 2021

Last Updated

February 6, 2023

Record last verified: 2023-02

Locations

DE(17)IT(2)