Ticagrelor for Acute Coronary Syndrome

(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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine which combination of medications is better and safer for individuals who have experienced acute coronary syndrome (ACS), including heart attacks. The study compares two drug pairs: ticagrelor (also known as Brilinta, Brilique, or Possia) with aspirin, and clopidogrel (also known as Plavix) with aspirin. Individuals who have recently experienced an ACS event and are prescribed these treatments might be suitable candidates. Participants will be grouped based on the timing of their treatment initiation, with no additional visits required, as the study monitors them through their medical records. As a Phase 4 trial, this study involves treatments that are already FDA-approved and proven effective, aiming to understand how they benefit a broader patient population.

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.

What is the safety track record for these treatments?

Research has shown that ticagrelor has been tested for safety in over 27,000 people, with more than half using it for at least a year. Common side effects include bleeding and shortness of breath. Clopidogrel has been studied in over 54,000 people, with more than 21,000 using it for a year or more. It may increase the risk of bleeding during surgeries or certain medical procedures. Both medications are generally well-tolerated, but each has specific side effects to consider. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Ticagrelor because, unlike standard treatments like Clopidogrel, it offers a faster onset of action and does not require metabolic activation. Ticagrelor works by directly inhibiting the P2Y12 receptor on platelets, which helps prevent blood clots more efficiently. This direct action not only makes it potentially more effective but also provides a more consistent antiplatelet effect, reducing the risk of variability seen in patients who take Clopidogrel.

What evidence suggests that this trial's treatments could be effective for dual antiplatelet therapy?

In this trial, participants will receive either ticagrelor or clopidogrel, both combined with aspirin. Research has shown that ticagrelor, when taken with aspirin, can reduce heart-related problems in people with acute coronary syndrome (ACS), as demonstrated in the PLATO study. However, a review of several studies found that ticagrelor was not superior to clopidogrel in preventing major heart issues and had a higher risk of causing bleeding. Clopidogrel, on the other hand, has been proven to significantly lower the risk of heart attacks and the need for additional heart procedures compared to aspirin alone. It is important to note that clopidogrel may not be as effective in individuals who do not process the drug efficiently. Overall, both medications are effective, but their efficacy can depend on individual patient factors. ^{4 5 6 7 8}

Who Is on the Research Team?

James Brophy, MD, PhD

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Acetylsalicylic acid (ASA)
• Clopidogrel
• Ticagrelor

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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 (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]

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]

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]

Citations

1. ahajournals.org ahajournals.org/doi/10.1161/circoutcomes.117.004194

Clinical Outcomes of Plavix and Generic Clopidogrel for ... At 1 year, 17.6% of patients prescribed Plavix and 17.9% of patients prescribed clopidogrel experienced the primary outcome (hazard ratio, 1.02; ...

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK470539/

Clopidogrel - StatPearls - NCBI Bookshelf When taken with a standard breakfast, the inhibition of ADP-induced platelet aggregation was reduced by less than 9%. The area under the curve ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40539811/

Efficacy and Safety of Clopidogrel Versus Aspirin ... Clopidogrel significantly reduced MI (risk ratio = 0.71; 95% confidence interval: 0.55-0.92; P = 0.01) and target-vessel revascularization (risk ...

4. fda.gov fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-reduced-effectiveness-plavix-clopidogrel-patients-who-are-poor

Reduced effectiveness of Plavix in patients who are poor ... In these patients, Plavix has less effect on platelets, and therefore less ability to prevent heart attack, stroke, and cardiovascular death. It ...

5. jacc.org jacc.org/doi/10.1016/j.jacasi.2022.12.007

Cost-Effectiveness of Clopidogrel vs Aspirin Monotherapy ... In the analogous UK and U.S. models, clopidogrel monotherapy was projected to decrease health care costs by £1,122 and $8,920 per patient ...

6. cdn.pfizer.com cdn.pfizer.com/pfizercom/products/material_safety_data/PZ01528.pdf

MATERIAL SAFETY DATA SHEET Releases to the environment should be avoided. Mobility, Persistence and. Degradability: Not readily biodegradable ( 4.07 % after 28 days). (Clopidogrel).

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2016/020839s062s064lbl.pdf

PLAVIX (clopidogrel bisulfate) tablets, for oral use Plavix has been evaluated for safety in more than 54,000 patients, including over 21,000 patients treated for one year or more. The clinically important adverse ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/clopidogrel-oral-route/description/drg-20063146

Clopidogrel (oral route) - Side effects & dosage Clopidogrel may increase the risk of serious bleeding during a surgery, other medical procedures (eg, coronary stent procedure), or some kinds ...