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Trial record 89 of 617 for:    ASPIRIN AND clopidogrel

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 : August 20, 2019
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

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.


Condition or disease Intervention/treatment Phase
Acute Coronary Syndrome Drug: Ticagrelor 90mg Drug: Clopidogrel 75mg Drug: acetylsalicylic acid (ASA) 81mg Phase 4

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


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Ticagrelor Compared to Clopidogrel in Acute Coronary Syndromes - the TC4 Comparative Effectiveness Study
Actual Study Start Date : October 1, 2018
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : March 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ticagrelor 90mg
Ticagrelor: 180 mg loading dose followed by 90 mg BID. Aspirin: 325 loading dose followed by 81 mg daily.
Drug: Ticagrelor 90mg
Ticagrelor tablet
Other Name: Brilinta

Drug: acetylsalicylic acid (ASA) 81mg
acetylsalicylic acid tablet
Other Name: Aspirin

Active Comparator: Clopidogrel 75mg
Clopidogrel: 300 mg loading dose followed by 75 mg daily. Aspirin: 325 loading dose followed by 81 mg daily.
Drug: Clopidogrel 75mg
Clopidogrel tablet
Other Name: Plavix

Drug: acetylsalicylic acid (ASA) 81mg
acetylsalicylic acid tablet
Other Name: Aspirin




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. The hazard ratio for the number of participants with any cardiovascular-related mortality event [ Time Frame: 12 months ]
  5. The hazard ratio for the number of participants with any acute MI event [ Time Frame: 12 months ]
  6. The hazard ratio for the number of participants with any stroke event [ Time Frame: 12 months ]
  7. The hazard ratio for the number of participants with any major bleeding requiring hospitalization event [ Time Frame: 12 months ]
  8. The hazard ratio for the number of participants with any recurrent coronary revascularization(s) event [ Time Frame: 12 months ]
  9. The hazard ratio for the number of participants with any reported drug side effects [ Time Frame: 12 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04057300


Contacts
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Contact: Nina Mamishi, RN, MSc 514 934-1934 ext 36278 ninamamishi@gmail.com
Contact: Stephen Kutcher, MSc stephen.kutcher@mail.mcgill.ca

Locations
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Canada, Quebec
McGill University Health Centre Recruiting
Montreal, Quebec, Canada
Contact: Nina Mamishi, RN, MSc       nina.mamishi@mail.mcgill.ca   
Principal Investigator: James Brophy, MD, PhD         
Sub-Investigator: Sonny Dandona, MD         
Sponsors and Collaborators
McGill University Health Centre/Research Institute of the McGill University Health Centre
Canadian Institutes of Health Research (CIHR)
Investigators
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Principal Investigator: James Brophy, MD, PhD McGill University Health Centre/Research Institute of the McGill University Health Centre

Publications:
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.

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Responsible Party: James Brophy, Principle Investigator, McGill University Health Centre/Research Institute of the McGill University Health Centre
ClinicalTrials.gov Identifier: NCT04057300     History of Changes
Other Study ID Numbers: TC4/2019-4530
First Posted: August 15, 2019    Key Record Dates
Last Update Posted: August 20, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by James Brophy, McGill University Health Centre/Research Institute of the McGill University Health Centre:
Cardiovascular disease
Myocardial Infarction
Stroke
Clopidogrel
Ticagrelor
Platelet Aggregation Inhibitors
Pragmatic Trial
Additional relevant MeSH terms:
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Aspirin
Clopidogrel
Acute Coronary Syndrome
Syndrome
Disease
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Ticagrelor
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents