Ticagrelor Compared to Clopidogrel in Acute Coronary Syndromes

NCT04057300 | Completed Phase 4

• 1 other identifier: TC4/2019-4530
• Study Type: interventional
• Target: 1,038
• Locations: 1 country
• Sites: 1

Brief Summary

The McGill University Health Center (MUHC) Division of Cardiology, with funding from the Canadian Institute of Health Research, is performing this randomized controlled trial to determine which dual antiplatelet therapy (DAPT), ticagrelor + aspirin (T+A) or clopidogrel and aspirin (C+A), is the most effective and safest for our patients. While the PLATO trial reported that T+A was superior, the prespecified group of North American patients (about 1/10 of the total study sample) actually did better with C+A, although this difference was not statistically significant. When the FDA approved T, they also stated: "Lack of Robustness of PLATO Superiority with Failure in the US Makes a Confirmatory Study Mandatory." As no confirmatory study has been done, this TC4 study aims to fill that void. Study design: A cluster randomization design, so all patients will receive either T+A or C+A, depending on the month they arrive at the MUHC when they start their DAPT. We will follow patients through their electronic health records. The patients have no follow-up visits for this research project.

Conditions

Acute Coronary Syndrome

Keywords

Cardiovascular disease; Myocardial Infarction; Stroke; Clopidogrel; Ticagrelor; Platelet Aggregation Inhibitors; Pragmatic Trial

Outcome Measures

Primary Outcomes (1)

• The hazard ratio for the number of participants that develop the outcome, a composite of cardiovascular-related mortality, myocardial infarction (MI), or stroke.

  ICD-10 Codes

  12 months

Secondary Outcomes (9)

• The primary outcome (The hazard ratio for the number of participants that develop the outcome, a composite of cardiovascular-related mortality, myocardial infarction (MI), or stroke) stratified by sex.

  12 months

• The hazard ratio for the number of participants that develop the outcome, a composite of cardiovascular-related mortality, myocardial infarction (MI), or stroke.

  36 months

• The primary outcome (The hazard ratio for the number of participants that develop the outcome, a composite of cardiovascular-related mortality, myocardial infarction (MI), or stroke) stratified by sex

  36 months

• The hazard ratio for the number of participants with any cardiovascular-related mortality event

  12 months

• The hazard ratio for the number of participants with any acute MI event

  12 months

Study Arms (2)

Ticagrelor 90mg

EXPERIMENTAL

Ticagrelor: 180 mg loading dose followed by 90 mg BID. Aspirin: 325 loading dose followed by 81 mg daily.

Drug: Ticagrelor 90mg; Drug: acetylsalicylic acid (ASA) 81mg

Clopidogrel 75mg

ACTIVE COMPARATOR

Clopidogrel: 300 mg loading dose followed by 75 mg daily. Aspirin: 325 loading dose followed by 81 mg daily.

Drug: Clopidogrel 75mg; Drug: acetylsalicylic acid (ASA) 81mg

Interventions

Ticagrelor 90mg DRUG

Ticagrelor tablet

Also known as: Brilinta

Ticagrelor 90mg

Clopidogrel 75mg DRUG

Clopidogrel tablet

Also known as: Plavix

Clopidogrel 75mg

acetylsalicylic acid (ASA) 81mg DRUG

acetylsalicylic acid tablet

Also known as: Aspirin

Clopidogrel 75mg; Ticagrelor 90mg

Eligibility Criteria

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

You may qualify if:

• Patients that are prescribed a dual-antiplatelet therapy (DAPT) regimen following an acute coronary syndrome (ACS) event.
• ACS, with or without ST-segment elevation.
• STEMI and NSTEMI positive biomarkers and appropriate ECG changes will be required.
• Patients provided written informed consent.

You may not qualify if:

• A decision from the patients attending physician to circumvent randomization and assign the patient a specific dual-antiplatelet therapy regimen.
• A contraindication to clopidogrel or ticagrelor
• Patients diagnosed with chronic total occlusion percutaneous coronary intervention (CTO PCI)

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

McGill University Health Centre

Montreal, Quebec, Canada

Location

Related Publications (6)

• 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

• Mehta SR, Bainey KR, Cantor WJ, Lordkipanidze M, Marquis-Gravel G, Robinson SD, Sibbald M, So DY, Wong GC, Abunassar JG, Ackman ML, Bell AD, Cartier R, Douketis JD, Lawler PR, McMurtry MS, Udell JA, van Diepen S, Verma S, Mancini GBJ, Cairns JA, Tanguay JF; members of the Secondary Panel. 2018 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology Focused Update of the Guidelines for the Use of Antiplatelet Therapy. Can J Cardiol. 2018 Mar;34(3):214-233. doi: 10.1016/j.cjca.2017.12.012. Epub 2017 Dec 19.

  PMID: 29475527 BACKGROUND

• Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L, Mehran R, Mukherjee D, Newby LK, O'Gara PT, Sabatine MS, Smith PK, Smith SC Jr. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016 Sep 6;68(10):1082-115. doi: 10.1016/j.jacc.2016.03.513. Epub 2016 Mar 29. No abstract available.

  PMID: 27036918 BACKGROUND

• Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators; Freij A, Thorsen M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57. doi: 10.1056/NEJMoa0904327. Epub 2009 Aug 30.

  PMID: 19717846 BACKGROUND

• Center for Drug Evaluation and Research. Complete Response Review Addendum Sponsor Safety Reporting Submissions: NDA 22-433 and IND 65,808 SD 632 Drug: ticagrelor (BrilintaTM). 2011. https://wwwaccessdatafdagov/drugsatfda_docs/nda/2011/022433Orig1s000MedRpdf.

  BACKGROUND

• Kutcher SA, Dendukuri N, Dandona S, Nadeau L, Brophy JM. Ticagrelor Compared to Clopidogrel in Acute Coronary Syndromes trial (TC4): a Bayesian pragmatic cluster randomized controlled trial. CMAJ. 2025 Mar 30;197(12):E309-E318. doi: 10.1503/cmaj.241862.

  PMID: 40164463 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome; Cardiovascular Diseases; Myocardial Infarction; Stroke

Interventions

Ticagrelor; Clopidogrel; Aspirin

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System 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; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• James Brophy, MD, PhD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

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: Principle Investigator

Study Record Dates

• First Submitted: August 13, 2019
• First Posted: August 15, 2019
• Study Start: October 1, 2018
• Primary Completion: April 1, 2022
• Study Completion: April 1, 2023
• Last Updated: November 3, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)