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Trial record 85 of 361 for:    ASPIRIN AND clopidogrel AND Purinergic Antagonists

Ticagrelor Compared to Clopidogrel in Acute Coronary Syndromes (TC4)

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ClinicalTrials.gov Identifier: NCT04057300
Recruitment Status : Recruiting
First Posted : August 15, 2019
Last Update Posted : September 2, 2020
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
James Brophy, McGill University Health Centre/Research Institute of the McGill University Health Centre

Tracking Information
First Submitted Date  ICMJE August 13, 2019
First Posted Date  ICMJE August 15, 2019
Last Update Posted Date September 2, 2020
Actual Study Start Date  ICMJE October 1, 2018
Estimated Primary Completion Date March 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 15, 2019)
The hazard ratio for the number of participants that develop the outcome, a composite of cardiovascular-related mortality, myocardial infarction (MI), or stroke. [ Time Frame: 12 months ]
ICD-10 Codes
Original Primary Outcome Measures  ICMJE
 (submitted: August 13, 2019)
Composite outcome of cardiovascular related mortality, myocardial infarction (MI), or stroke. [ Time Frame: 12 months ]
ICD-10 Codes
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 15, 2019)
  • 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. [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 36 months ]
  • The hazard ratio for the number of participants with any cardiovascular-related mortality event [ Time Frame: 12 months ]
  • The hazard ratio for the number of participants with any acute MI event [ Time Frame: 12 months ]
  • The hazard ratio for the number of participants with any stroke event [ Time Frame: 12 months ]
  • The hazard ratio for the number of participants with any major bleeding requiring hospitalization event [ Time Frame: 12 months ]
  • The hazard ratio for the number of participants with any recurrent coronary revascularization(s) event [ Time Frame: 12 months ]
  • The hazard ratio for the number of participants with any reported drug side effects [ Time Frame: 12 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2019)
  • The primary outcome (composite of CV-related death/MI/stroke) stratified by sex [ Time Frame: 12 months ]
  • The individual outcomes of CV-related mortality, acute MI, stroke, major bleeding requiring hospitalization, recurrent coronary revascularizations, patient drug compliance, and drug side effects [ Time Frame: 12 months ]
  • The individual outcomes of CV-related mortality, acute MI, stroke, major bleeding requiring hospitalization, recurrent coronary revascularizations, patient drug compliance, and drug side effects [ Time Frame: 36 months ]
  • Composite outcome of cardiovascular related mortality, myocardial infarction (MI), or stroke. [ Time Frame: 36 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ticagrelor Compared to Clopidogrel in Acute Coronary Syndromes
Official Title  ICMJE Ticagrelor Compared to Clopidogrel in Acute Coronary Syndromes - the TC4 Comparative Effectiveness Study
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.

Detailed Description

Acute Coronary Syndrome (ACS) is most often caused by erosion or rupture of an atherosclerotic plaque associated with inflammation, thrombus formation, vasoconstriction, and microembolisation. In unremitting circumstances, thrombosis at the site of plaque rupture or erosion leads to complete compromise of coronary blood flow and ultimately myocardial infarction (MI). Platelet adhesion, activation and aggregation, therefore, play key roles in the transformation of a stable atherosclerotic plaque to an unstable lesion and antiplatelet drugs have become a mainstay in the prevention of recurrent cardiovascular events.

A large multicenter RCT (PLATO) showed a statistically significant decrease in composite CV outcomes with the newer ticagrelor compared to clopidogrel. This has prompted both European and Canadian guideline writers to endorse ticagrelor/aspirin as the DAPT of choice. However residual uncertainties regarding the choice of DAPT are highlighted by the PLATO subgroup analysis that showed an increased risk with ticagrelor in North America (NA) patients. This led to delayed FDA approval, dissenting FDA reviews and a reluctance in US guidelines to recommend the ticagrelor DAPT regime over others.

The main area of uncertainty, at least from the NA perspective, hinges on the small number of NA patients randomized in the PLATO trial and their increased risk with ticagrelor (n=1814, HR 1.25; 95% CI 0.93 - 1.67). The risk in NA patients was statistically significantly different from the benefit seen in the other subgroups (P=0.04) and the crux of the debate is then whether to believe the subgroup analysis or the combined study results (n=18624, HR, 0.84; 95% CI 0.77 to 0.92). The complete study provides maximal information but perhaps at a cost of being less representative of what to expect in NA practice. Conventional statistical paradigms would say that given the pre-specified nature of the geographic subgroup analysis and given the statistically significant interaction observed, one should concentrate on the subgroup results and not the combined results.

The conventional statistical model used in the PLATO analysis subsumes that every patient, regardless of differences in recruitment characteristics or ancillary treatment strategies received in the different regions, is completely identical in their response to the studied intervention. It seems highly unlikely that patients from the 43 PLATO enrolling countries are truly identical in their drug response given recruitment, genetic and background treatment variations.

This project will resolve these uncertainties and address the crucial clinical question of which DAPT regime is best after an ACS? This proposal will double the currently available evidence with a novel research design using inexpensive, electronic data and will provide a feasible answer to this important clinical question.

More information can be found here:

https://brophyj.github.io/index.html

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Coronary Syndrome
Intervention  ICMJE
  • Drug: Ticagrelor 90mg
    Ticagrelor tablet
    Other Name: Brilinta
  • Drug: Clopidogrel 75mg
    Clopidogrel tablet
    Other Name: Plavix
  • Drug: acetylsalicylic acid (ASA) 81mg
    acetylsalicylic acid tablet
    Other Name: Aspirin
Study Arms  ICMJE
  • Experimental: Ticagrelor 90mg
    Ticagrelor: 180 mg loading dose followed by 90 mg BID. Aspirin: 325 loading dose followed by 81 mg daily.
    Interventions:
    • Drug: Ticagrelor 90mg
    • Drug: acetylsalicylic acid (ASA) 81mg
  • Active Comparator: Clopidogrel 75mg
    Clopidogrel: 300 mg loading dose followed by 75 mg daily. Aspirin: 325 loading dose followed by 81 mg daily.
    Interventions:
    • Drug: Clopidogrel 75mg
    • Drug: acetylsalicylic acid (ASA) 81mg
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 13, 2019)
1500
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2021
Estimated Primary Completion Date March 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.
  • NSTEMI patients with negative biomarkers are generally considered as unstable angina and will also be eligible for study inclusion if their treating physician has determined that DAPT is appropriate.
  • Patients provided written informed consent.

Exclusion Criteria:

  • 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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Nina Mamishi, RN, MSc 514 934-1934 ext 36278 ninamamishi@gmail.com
Contact: Stephen Kutcher, MSc stephen.kutcher@mail.mcgill.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04057300
Other Study ID Numbers  ICMJE TC4/2019-4530
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party James Brophy, McGill University Health Centre/Research Institute of the McGill University Health Centre
Study Sponsor  ICMJE McGill University Health Centre/Research Institute of the McGill University Health Centre
Collaborators  ICMJE Canadian Institutes of Health Research (CIHR)
Investigators  ICMJE
Principal Investigator: James Brophy, MD, PhD McGill University Health Centre/Research Institute of the McGill University Health Centre
PRS Account McGill University Health Centre/Research Institute of the McGill University Health Centre
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP