Ticagrelor Compared to Clopidogrel in Acute Coronary Syndromes

(TC4 Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 4

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

Must be taking: Dual-antiplatelet therapy

Disqualifiers: Contraindication to clopidogrel, ticagrelor, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

1038 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you will be assigned a specific dual-antiplatelet therapy (either ticagrelor + aspirin or clopidogrel + aspirin) based on when you start the trial.

Is ticagrelor safe for human use?

Ticagrelor is generally well tolerated in humans, but it can cause some side effects like bleeding, shortness of breath, and heart rhythm issues. It has been shown to be safe in studies, but it does have a warning for bleeding risks, which is common for drugs that prevent blood clots. ^{1 2 3 4 5}

How does the drug Ticagrelor differ from other treatments for acute coronary syndrome?

Ticagrelor is unique because it is a reversible platelet inhibitor that works faster and more effectively than clopidogrel, leading to quicker recovery of platelet function when the drug is stopped. It also reduces the risk of death from vascular causes, heart attacks, or strokes more significantly than clopidogrel, without increasing major bleeding, although it may cause more non-procedure-related bleeding. ^{3 4 6 7 8}

What is the purpose of this trial?

This trial is testing two combinations of blood-thinning medications to find out which is safer and more effective for patients with heart problems. The medications help prevent blood cells from forming clots, reducing the risk of heart attacks.

Research Team

James Brophy, MD, PhD

Principal Investigator

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

Eligibility 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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ticagrelor + aspirin or clopidogrel + aspirin based on the month of arrival

12 months

Follow-up

Participants are monitored through electronic health records for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Acetylsalicylic acid (ASA)
• Clopidogrel
• Ticagrelor

Participant Groups

Group I: Ticagrelor 90mg Experimental Treatment 2 Interventions

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

Group II: Clopidogrel 75mg Active Control 2 Interventions

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

Clopidogrel is already approved in European Union, United States, Canada, Japan, China for the following indications:

Approved in European Union as Plavix for:

• Prevention of atherothrombotic events in patients with myocardial infarction, stroke, or peripheral arterial disease
• Acute coronary syndrome

Approved in United States as Plavix for:

• Reduction of myocardial infarction and stroke in patients with acute coronary syndrome
• Reduction of myocardial infarction and stroke in patients with recent myocardial infarction, recent stroke, or established peripheral arterial disease

Approved in Canada as Plavix for:

• Prevention of atherothrombotic events in patients with myocardial infarction, stroke, or peripheral arterial disease
• Acute coronary syndrome

Approved in Japan as Plavix for:

• Prevention of recurrence of ischemic cerebrovascular disorder
• Prevention of recurrence of myocardial infarction

Approved in China as Plavix for:

• Prevention of atherothrombotic events in patients with myocardial infarction, stroke, or peripheral arterial disease
• Acute coronary syndrome

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

476

Recruited

170,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Findings from Research

In the large PLATO study involving adult patients with acute coronary syndromes (ACS), ticagrelor was found to be more effective than clopidogrel in reducing the risk of major cardiovascular events, including myocardial infarction and stroke, while also showing a trend towards reduced all-cause mortality.

Ticagrelor was generally well tolerated, with no increased risk of major bleeding compared to clopidogrel, although it did have higher rates of certain non-hemorrhagic side effects like dyspnea and ventricular pauses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor: a review of its use in adults with acute coronary syndromes. Dhillon, S.[2018]

Ticagrelor (Brilinta™) was approved by the FDA for treating acute coronary syndromes based on the PLATO trial, which involved 18,624 patients and compared its efficacy to clopidogrel over 6-12 months.

Despite its approval, there were significant concerns from FDA reviewers regarding its efficacy and safety, particularly related to bleeding risks and the potential reduction in effectiveness when used with high doses of aspirin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor FDA approval issues revisited. Serebruany, VL.[2018]

Ticagrelor (Brilinta) has been approved by the FDA as an oral antiplatelet medication to be used with low-dose aspirin for reducing thrombotic cardiovascular events in patients with acute coronary syndrome (ACS).

Ticagrelor will compete with existing medications like clopidogrel (Plavix) and prasugrel (Effient), especially as clopidogrel is expected to become available as a generic option soon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor (Brilinta)--better than clopidogrel (Plavix)? [2018]

Ticagrelor is an effective oral antiplatelet medication commonly used in patients with acute coronary syndrome and after procedures like PCI, acting as a reversible inhibitor of the P2Y12 receptor.

Despite its efficacy, Ticagrelor can cause bradyarrhythmias and ventricular pauses, as demonstrated in a case study of a 58-year-old man who experienced syncope after loading with the drug, highlighting the need for monitoring its cardiac effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor-Induced Syncope/Bradyarrhythmia. Kotaru, V., Kalavakunta, JK.[2021]

In a study involving 29 healthy volunteers, the generic drug Ticaloguard® was found to have similar therapeutic effects and safety profiles compared to the brand-name drug Brilique® in terms of platelet aggregation, indicating that it can be used interchangeably in treating acute coronary syndrome.

The study emphasizes the importance of testing the therapeutic equivalence of generic drugs, especially for critical medications, rather than relying solely on bioequivalence, to ensure patient safety and effective treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testing P2Y12 platelet inhibitors generics beyond bioequivalence: a parallel single-blinded randomized trial. Zarif, B., Soliman, L., Sabry, NA., et al.[2022]

In a study of 81 cardiac surgical patients, those who continued taking ticagrelor with acetylsalicylic acid (ASA) until surgery experienced significantly higher blood loss and required more blood product transfusions compared to those on clopidogrel with ASA.

Despite the increased bleeding and transfusion needs in the ticagrelor group, there were no significant differences in intensive care unit stay, hospital stay, or mortality rates, indicating that while ticagrelor may pose bleeding risks, it does not adversely affect overall survival or recovery in the short term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of cardiac surgery patients with ongoing ticagrelor therapy: boon and bane of a new drug. Schotola, H., Bräuer, A., Meyer, K., et al.[2018]

Ticagrelor, a potent oral platelet inhibitor, significantly reduces the risk of death, myocardial infarction, or stroke in patients with acute coronary syndromes compared to clopidogrel, as shown in the PLATO study.

While ticagrelor does not increase the overall rate of major bleeding compared to clopidogrel, it is associated with a higher incidence of non-procedure-related bleeding, indicating a need for careful monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Medication of the month. Ticagrelor (Brilique): potent oral antagonist of platelet activity]. Lancellotti, P.[2018]

Ticagrelor is a new type of P2Y(12) antagonist that works differently from traditional antiplatelet medications like clopidogrel and prasugrel, providing a potentially more effective option for treating acute coronary syndromes.

Clinical trials have shown that ticagrelor, when used with aspirin, has a favorable safety profile and can overcome some limitations associated with clopidogrel, making it a valuable addition to antiplatelet therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor: a P2Y12 antagonist for use in acute coronary syndromes. Wijeyeratne, YD., Joshi, R., Heptinstall, S.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Ticagrelor: a review of its use in adults with acute coronary syndromes. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Ticagrelor FDA approval issues revisited. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Ticagrelor (Brilinta)--better than clopidogrel (Plavix)? [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Ticagrelor-Induced Syncope/Bradyarrhythmia. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Testing P2Y12 platelet inhibitors generics beyond bioequivalence: a parallel single-blinded randomized trial. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of cardiac surgery patients with ongoing ticagrelor therapy: boon and bane of a new drug. [2018]

7. Belgium pubmed.ncbi.nlm.nih.gov

[Medication of the month. Ticagrelor (Brilique): potent oral antagonist of platelet activity]. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Ticagrelor: a P2Y12 antagonist for use in acute coronary syndromes. [2022]