Platelet Inhibition With Ticagrelor 60 mg Versus Ticagrelor 90 mg in Elderly Patients With ACS

NCT04739384 | Completed Phase 3

• 1 other identifier: 16520
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Elderly individuals are increasingly represented among patients with acute coronary syndrome (ACS). Dual antiplatelet therapy (DAPT) with aspirin and an oral P2Y12 receptor inhibitor has an established role in the prevention of atherothrombotic events in ACS setting. However, DAPT in older patients is challenged by a concurrent heightened risk of ischemia and bleeding. Although guidelines recommend DAPT with aspirin and ticagrelor for elderly patients with ACS, clopidogrel, a less potent antiplatelet agent, continues to be used in more than one third of ACS patients with elderly status being the strongest predictor of undertreatment. A lower dose of ticagrelor may represent an alternative to the standard dose by conferring a similar efficacy and, potentially, a better safety profile. Our prospective, randomized, double-blind, crossover trial will test the hypothesis that a lower dose of ticagrelor provides similar antiplatelet effects compared with a standard dose among elderly patients with ACS. The main aim of the trial is to determine the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 mg twice daily versus ticagrelor 90 mg twice daily among elderly patients with ACS undergoing PCI. This will be a prospective, randomized (1:1 ratio), non-inferiority, open-label, crossover trial to evaluate the level of platelet inhibition achieved with a low-dose of ticagrelor (60 mg twice daily) versus a standard dose of ticagrelor (90 mg twice daily) among elderly patients with ACS undergoing PCI.

Conditions

Acute Coronary Syndrome; STEMI; NSTEMI; Coronary Artery Disease; Myocardial Infarction

Keywords

Platelet aggregation; Elderly patients; Ticagrelor

Outcome Measures

Primary Outcomes (1)

• P2Y12 reaction units (PRU) determined by VerifyNow assay.

  Comparison of pre-dose P2Y12 reaction units (PRU) determined by VerifyNow- P2Y12 assay at 14 days after treatment with ticagrelor 60 mg or 90 mg.

  14 days

Secondary Outcomes (9)

• High platelet reactivity (HPR) and ADP-induced platelet reactivity.

  28 days

• Non ADP-induced platelet reactivity.

  28 days

• The composite of all-cause death, myocardial infarction, or stroke.

  28 days

• The composite of cardiovascular death, myocardial infarction, urgent target-lesion revascularization.

  28 days

• Frequency of spontaneous myocardial infarction.

  28 days

Study Arms (2)

Standard dose of ticagrelor (90 mg twice daily).

EXPERIMENTAL

Standard dose of ticagrelor (90 mg twice daily) followed by lower dose of ticagrelor (60 mg twice daily).

Drug: Ticagrelor 90mg; Drug: Ticagrelor 60 mg

Low dose of ticagrelor (60 mg twice daily).

EXPERIMENTAL

Low dose of ticagrelor (60 mg twice daily) followed by standard dose of ticagrelor (90 mg twice daily).

Drug: Ticagrelor 90mg; Drug: Ticagrelor 60 mg

Interventions

Ticagrelor 90mg DRUG

Ticagrelor 90 mg followed by Ticagrelor 60 mg

Also known as: Ticagrelor 60 mg

Low dose of ticagrelor (60 mg twice daily).; Standard dose of ticagrelor (90 mg twice daily).

Ticagrelor 60 mg DRUG

Ticagrelor 60 mg followed by Ticagrelor 90 mg

Also known as: Ticagrelor 90 mg

Low dose of ticagrelor (60 mg twice daily).; Standard dose of ticagrelor (90 mg twice daily).

Eligibility Criteria

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

You may qualify if:

• Ability to provide written informed consent in a time window 1 to 3 days after successful PCI;
• Male or female, age ≥ 75 years at screening;
• ACS at the time of the index hospitalization;
• Use of a loading dose of 180 mg of ticagrelor administered after diagnosis of ACS or after PCI;
• Use of a maintenance dose of 90 mg twice daily of ticagrelor of at least 48 hours after the loading dose;
• Successful PCI (Thrombolysis In Myocardial Infarction \[TIMI\] flow 3 and residual coronary stenosis \<30%) for non-ST-segment elevation ACS or ST-segment elevation myocardial infarction

You may not qualify if:

• Use of glycoprotein IIb/IIIa receptor inhibitors;
• Need for chronic oral anticoagulant therapy;
• Prior fibrinolysis;
• Unstable clinical status (hemodynamic or electrical instability);
• Planned surgery requiring DAPT discontinuation during the study;
• Prior stroke, transient ischemic attack or intracranial bleeding;
• Active bleeding;
• Severe anemia (hemoglobin \< 8g/dL);
• Platelet count ≤80x103/ml;
• Renal failure (hemodialysis or creatinine clearance ≤ 30 ml/min calculated with Cockroft-Gault formula);
• Severe hepatic dysfunction (baseline alanine aminotransferase ≥ 2.5 times the upper limit of normal);
• Known hypersensitivity or contraindication to ticagrelor;
• Under judicial protection, tutorship or curatorship;
• Unable to understand and follow study-related instructions;
• Enrollment in another investigational device or drug study.

Sponsors & Collaborators

• Federico II University: lead
• AdvicePharma Group: collaborator

Study Sites (1)

Professor Giovanni Esposito

Naples, 80131, Italy

Location

Related Publications (11)

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• Varenne O, Cook S, Sideris G, Kedev S, Cuisset T, Carrie D, Hovasse T, Garot P, El Mahmoud R, Spaulding C, Helft G, Diaz Fernandez JF, Brugaletta S, Pinar-Bermudez E, Mauri Ferre J, Commeau P, Teiger E, Bogaerts K, Sabate M, Morice MC, Sinnaeve PR; SENIOR investigators. Drug-eluting stents in elderly patients with coronary artery disease (SENIOR): a randomised single-blind trial. Lancet. 2018 Jan 6;391(10115):41-50. doi: 10.1016/S0140-6736(17)32713-7. Epub 2017 Nov 1.

  PMID: 29102362 BACKGROUND

• Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Juni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN; ESC Scientific Document Group; ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2018 Jan 14;39(3):213-260. doi: 10.1093/eurheartj/ehx419. No abstract available.

  PMID: 28886622 BACKGROUND

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  PMID: 29544348 BACKGROUND

• Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001-15. doi: 10.1056/NEJMoa0706482. Epub 2007 Nov 4.

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• Savonitto S, Ferri LA, Piatti L, Grosseto D, Piovaccari G, Morici N, Bossi I, Sganzerla P, Tortorella G, Cacucci M, Ferrario M, Murena E, Sibilio G, Tondi S, Toso A, Bongioanni S, Ravera A, Corrada E, Mariani M, Di Ascenzo L, Petronio AS, Cavallini C, Vitrella G, Rogacka R, Antonicelli R, Cesana BM, De Luca L, Ottani F, De Luca G, Piscione F, Moffa N, De Servi S; Elderly ACS 2 Investigators. Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization. Circulation. 2018 Jun 5;137(23):2435-2445. doi: 10.1161/CIRCULATIONAHA.117.032180. Epub 2018 Feb 19.

  PMID: 29459361 BACKGROUND

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  PMID: 25773268 BACKGROUND

• Storey RF, Angiolillo DJ, Bonaca MP, Thomas MR, Judge HM, Rollini F, Franchi F, Ahsan AJ, Bhatt DL, Kuder JF, Steg PG, Cohen M, Muthusamy R, Braunwald E, Sabatine MS. Platelet Inhibition With Ticagrelor 60 mg Versus 90 mg Twice Daily in the PEGASUS-TIMI 54 Trial. J Am Coll Cardiol. 2016 Mar 15;67(10):1145-1154. doi: 10.1016/j.jacc.2015.12.062.

  PMID: 26965534 BACKGROUND

• Piccolo R, Avvedimento M, Canonico ME, Gargiulo P, Paolillo R, Conti V, Dal Piaz F, Filippelli A, Morisco C, Simonetti F, Leone A, Marenna A, Bruzzese D, Gargiulo G, Stabile E, Di Serafino L, Franzone A, Cirillo P, Esposito G. Platelet Inhibition with Ticagrelor 60 mg Versus 90 mg Twice Daily in Elderly Patients with Acute Coronary Syndrome: Rationale and Design of the PLINY THE ELDER Trial. Cardiovasc Drugs Ther. 2023 Oct;37(5):1031-1038. doi: 10.1007/s10557-021-07302-y. Epub 2022 Jan 20.

  PMID: 35048203 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome; ST Elevation Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Coronary Artery Disease; Myocardial Infarction

Interventions

Ticagrelor

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases

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

• Giovanni Esposito, MD, PhD

  Federico II University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 28, 2020
• First Posted: February 4, 2021
• Study Start: April 1, 2021
• Primary Completion: June 20, 2022
• Study Completion: June 20, 2022
• Last Updated: July 7, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)