Short-term DAPT for Coronary Artery Disease

(ODIN Trial)

Recruiting at 11 trial locations

Overseen By Madeleine Wood

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Weill Medical College of Cornell University

Must not be taking: Oral anticoagulants, Strong CYP3A4 inhibitors

Disqualifiers: Atrial fibrillation, End-organ dysfunction, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

700 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 cannot participate if you are using oral anticoagulants or certain strong medications like ketoconazole or clarithromycin. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Ticagrelor for coronary artery disease?

Ticagrelor is an antiplatelet drug used to reduce the risk of heart-related events in patients with acute coronary syndrome, and it has been shown to be effective when used with aspirin. It works by preventing blood cells called platelets from clumping together, which helps prevent blood clots. ^{1 2 3 4 5}

How does the drug Ticagrelor differ from other treatments for coronary artery disease?

Ticagrelor is unique because it is a direct inhibitor of the ADP P2Y12 receptor, which means it doesn't need to be activated by the body to work, unlike some other drugs. It also has a rapid onset and offset of action, making it effective quickly and allowing for flexible treatment durations, such as short-term dual antiplatelet therapy (DAPT) followed by monotherapy, which can reduce bleeding risks compared to standard DAPT. ^{3 5 6 7 8}

What is the purpose of this trial?

The purpose of this study is to compare the effect of ticagrelor plus low-dose aspirin versus low-dose aspirin alone in patients with chronic coronary disease undergoing coronary artery bypass grafting.

Research Team

Marc Ruel, MD, MPH

Principal Investigator

Ottawa Heart Institute Research Corporation

Mario Gaudino, MD, PhD, MSCE

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for adults over 18 who need their first coronary artery bypass graft using a saphenous vein and can follow the study for at least 5 years. It's not for women who could get pregnant, people with recent heart issues or surgeries, those on blood thinners or with certain health conditions like severe liver failure, cancer, or expected short lifespan.

Inclusion Criteria

Ability to sign informed consent and comply with all study procedures, including follow-up for at least 5 years

I am having my first CABG surgery using at least one vein from my leg.

Exclusion Criteria

I have a type of irregular heartbeat known as atrial fibrillation.

I am a woman who could become pregnant.

I am not allergic to ticagrelor and do not have any current severe bleeding or a history of serious brain bleeding. I am not taking strong CYP3A4 inhibitors.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ticagrelor plus low-dose aspirin or low-dose aspirin alone for one month

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including imaging follow-up at 12 months

12 months

Long-term follow-up

Participants are monitored for long-term outcomes, including quality of life assessments over 5 years

5 years

Treatment Details

Interventions

• Ticagrelor
• Ticagrelor placebo

Trial Overview The study tests if Ticagrelor (a blood-thinning medication) is more effective than a placebo in preventing complications after coronary artery bypass surgery in patients with chronic coronary disease. Participants will be randomly assigned to receive either Ticagrelor or a placebo.

Participant Groups

Group I: Ticagrelor 90 mg + Low-Dose Aspirin Experimental Treatment 2 Interventions

Group II: Low-Dose Aspirin Alone Active Control 1 Intervention

Ticagrelor is already approved in United States, European Union for the following indications:

Approved in United States as Brilinta for:

• Acute coronary syndrome (ACS)
• Cardiovascular event prevention
• Coronary artery disease (CAD)
• Acute ischemic stroke
• Transient ischemic attack (TIA)

Approved in European Union as Brilique for:

• Acute coronary syndrome (ACS)
• Cardiovascular event prevention
• Coronary artery disease (CAD)
• Acute ischemic stroke
• Transient ischemic attack (TIA)

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Findings from Research

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 antiplatelet medication used in patients with acute coronary syndrome, helping to reduce the risk of heart attacks and other cardiovascular events.

Clinical studies have shown that ticagrelor provides a greater reduction in major adverse cardiovascular events compared to traditional treatments like clopidogrel, making it a preferred choice in acute settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ticagrelor (brilinta), an antiplatelet drug for acute coronary syndrome. Fuller, R., Chavez, B.[2021]

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 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 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 the TWILIGHT trial involving 5,769 patients, ticagrelor monotherapy after three months of dual antiplatelet therapy significantly reduced bleeding complications compared to ticagrelor plus aspirin, regardless of the type of drug-eluting stent used.

Ticagrelor monotherapy did not increase the risk of death, heart attack, or stroke, demonstrating its safety and efficacy as a bleeding avoidance strategy in high-risk patients undergoing percutaneous coronary intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of ticagrelor monotherapy according to drug-eluting stent type: the TWILIGHT-STENT study. Dangas, G., Baber, U., Sharma, S., et al.[2023]

In a meta-analysis of 26,143 patients, short-term dual antiplatelet therapy (DAPT) followed by ticagrelor monotherapy showed a 20% reduction in all-cause mortality and an 18% reduction in net adverse clinical events compared to standard DAPT, indicating improved efficacy.

This treatment strategy also significantly reduced the risk of major bleeding by 33%, suggesting a better safety profile while maintaining similar ischemic risk compared to standard DAPT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ticagrelor Monotherapy in Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis. Gelbenegger, G., Schoergenhofer, C., Jilma, B., et al.[2021]

Ticagrelor is more effective than clopidogrel in reducing the risk of cardiovascular death, myocardial infarction, and stroke in patients after acute coronary syndromes, as demonstrated in the PLATO trial.

Prolonged dual antiplatelet therapy with ticagrelor beyond 12 months may benefit certain patients at high risk for ischemic events, according to the PEGASUS TIMI 54 trial, and this approach has been endorsed by recent ACC/AHA guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of ticagrelor in the treatment of cardiac ischemia. Rosa, GM., Bianco, D., Valbusa, A., et al.[2018]

References

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

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

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

Ticagrelor (brilinta), an antiplatelet drug for acute coronary syndrome. [2021]

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

Ticagrelor-Induced Syncope/Bradyarrhythmia. [2021]

4. England pubmed.ncbi.nlm.nih.gov

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

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

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

6. France pubmed.ncbi.nlm.nih.gov

Safety and efficacy of ticagrelor monotherapy according to drug-eluting stent type: the TWILIGHT-STENT study. [2023]

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

Efficacy and Safety of Ticagrelor Monotherapy in Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis. [2021]

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

Pharmacokinetics and pharmacodynamics of ticagrelor in the treatment of cardiac ischemia. [2018]