Short-term DAPT for Coronary Artery Disease

(ODIN Trial)

Recruiting at 24 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding ticagrelor, a blood-thinning drug, to low-dose aspirin is more effective than aspirin alone for individuals with long-term coronary artery disease undergoing heart bypass surgery. Researchers aim to determine if this combination prevents complications after surgery. The trial includes two groups: one taking ticagrelor with aspirin and another taking only aspirin. Individuals undergoing their first planned heart bypass surgery who can use a saphenous vein may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that taking ticagrelor with aspirin can lower the risk of heart problems, such as heart attacks and strokes, in people with coronary artery disease. However, some safety concerns exist. Studies have found that while this combination can help prevent heart issues, it also increases the chance of serious bleeding compared to a placebo. This may lead to more cases of bleeding that require medical care.

Ticagrelor is already approved for people with high-risk coronary artery disease, indicating it is generally safe for most individuals. However, the increased risk of bleeding should be considered when deciding to join a trial. Consulting a healthcare provider is advisable to understand what these risks might mean personally. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for coronary artery disease?

Researchers are excited about the Ticagrelor 90 mg + low-dose aspirin combination because it offers a potentially safer and more effective alternative for treating coronary artery disease. Unlike standard treatments that typically require dual antiplatelet therapy (DAPT) with drugs like clopidogrel or prasugrel alongside aspirin for extended periods, this approach explores a shorter duration of DAPT. This could reduce the risk of bleeding, a common side effect associated with prolonged DAPT, while still maintaining cardiovascular protection. The use of Ticagrelor, known for its potent platelet inhibition, in a shorter regimen might strike the perfect balance between efficacy and safety, making it an exciting development in the management of coronary artery disease.

What evidence suggests that this trial's treatments could be effective for coronary artery disease?

In this trial, participants will receive either Ticagrelor 90 mg combined with low-dose aspirin or low-dose aspirin alone. Research has shown that ticagrelor, when taken with low-dose aspirin, benefits people with coronary artery disease. Studies found that ticagrelor lowered the risk of death from heart-related issues, heart attacks, and strokes compared to clopidogrel. In longer studies, using ticagrelor with aspirin slightly reduced serious heart problems compared to aspirin alone. However, more people stopped taking ticagrelor due to side effects. Overall, ticagrelor reduces the chance of a first heart attack or stroke in people at high risk. ^{1 2 3 4 5}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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]

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 (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.

academic.oup.com

academic.oup.com/ejcts/article/67/7/ezaf175/8145572

Extent of coronary artery disease and clinical outcomes with ...

In this post hoc analysis of the TICAB trial, we found no significant difference in the effect of ticagrelor monotherapy compared to aspirin on ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/24952862/

Extent of coronary artery disease and outcomes after ...

Ticagrelor, compared with clopidogrel, reduced the composite of cardiovascular death, myocardial infarction, and stroke in patients with extensive CAD.

3.

ahajournals.org

ahajournals.org/doi/10.1161/JAHA.123.031606

Review of the Ticagrelor Trials Evidence Base

After a median follow‐up of 40 months, DAPT compared with aspirin monotherapy resulted in a 0.8% absolute reduction in the primary composite end ...

4.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1908077

Ticagrelor in Patients with Stable Coronary Disease and ...

The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ...

5.

brilintahcp.com

brilintahcp.com/cad.html

Coronary Artery Disease (CAD) | BRILINTA | For HCPs

BRILINTA is indicated to reduce the risk of a first MI or stroke in patients with coronary artery disease (CAD) at high risk for such events.