Short-term DAPT for Coronary Artery Disease
(ODIN Trial)
Recruiting in Palo Alto (17 mi)
+11 other locations
Overseen byMarc Ruel, MD, MPH
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
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
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
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.
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.
12345How 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.
35678Eligibility 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 18 years old or older.
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.
+11 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Ticagrelor 90 mg + Low-Dose AspirinExperimental Treatment2 Interventions
Group II: Low-Dose Aspirin AloneActive Control1 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Ottawa Heart InstituteOttawa, Canada
Weill Cornell MedicineNew York, NY
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Who Is Running the Clinical Trial?
Weill Medical College of Cornell UniversityLead Sponsor
Canadian Institutes of Health Research (CIHR)Collaborator
References
Ticagrelor (Brilinta)--better than clopidogrel (Plavix)? [2018]The FDA has approved ticagrelor (Brilinta-AstraZeneca), an oral antiplatelet drug, for use with low-dose aspirin to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS). It will compete with clopidogrel (Plavix) and prasugrel (Effient) for such use. Clopidogrel is expected to become available generically in the US within the next few months.
Ticagrelor (brilinta), an antiplatelet drug for acute coronary syndrome. [2021]Ticagrelor (Brilinta) for acute coronary syndrome.
Ticagrelor-Induced Syncope/Bradyarrhythmia. [2021]Ticagrelor (BRILINTA®) is a very commonly used oral antiplatelet agent in acute coronary syndrome and after percutaneous coronary intervention (PCI). It is a reversible, direct inhibitor of the adenosine diphosphate (ADP) P2Y12 receptor. Most of the patients tolerate the drug well but it is known to cause brady arrhythmias and ventricular pauses, the exact mechanism of which is unclear. We present a case of acute coronary syndrome/unstable angina in a 58-year-old Caucasian gentleman requiring cardiac catheterization and PCI with drug eluting stent deployment and syncope following Ticagrelor loading from long ventricular pauses.
Ticagrelor: a P2Y12 antagonist for use in acute coronary syndromes. [2022]Agents that inhibit platelet function are used routinely in the treatment and prevention of acute coronary syndromes. The main antiplatelet treatments used combine aspirin with one of the thienopyridine P2Y(12) antagonists, either clopidogrel or prasugrel. By blocking the synthesis of thromboxane A(2) in platelets and by blocking the effects of ADP, respectively, these agents reduce platelet activity, platelet aggregation and thrombus formation. Ticagrelor (marketed by AstraZeneca as Brilinta™ in the USA, and as Brilique(®) or Possia(®) in Europe) is a cyclopentyl-triazolo-pyrimidine, a new chemical class of P2Y(12) antagonist that is now approved for use in the wide spectrum of acute coronary syndromes. In this article we provide an overview of ticagrelor. We discuss the differences in mode of action compared with other P2Y(12) antagonists, examine its pharmacodynamic, pharmacokinetic and safety profile, and summarize the various clinical trials that have provided information on its efficacy in combination with aspirin. Ticagrelor appears to overcome some of the difficulties that have been encountered with other antiplatelet treatments, clopidogrel in particular.
Testing P2Y12 platelet inhibitors generics beyond bioequivalence: a parallel single-blinded randomized trial. [2022]Cardiovascular diseases are the leading cause of death worldwide. Ticagrelor is an oral antiplatelet drug used in acute coronary syndrome. Although generic drugs are approved for their bioequivalence to the original product, they are not necessarily to be therapeutically equivalent. This study was conducted to prove the efficacy and safety of ticagrelor generically named Ticaloguard® compared to its brand Brilique® in healthy volunteers. A loading dose of 180 mg ticagrelor named Brilique® or Ticaloguard® followed by a 90 mg twice daily regimen as maintenance dose was given to 14 and 15 volunteers in Tica and Brili groups, respectively. The platelet aggregation on the ADP agonist was assessed at baseline and repeated 1 h and 3 h after the loading dose, on day 4 (after reaching steady-state), 12 and 24 h after discontinuation of the antiplatelet drug. Adverse effects from trial medications were noted by direct questions. It was shown that generic Ticaloguard® provides a similar therapeutic effect and safety as its branded Brilique® (p > 0.05). This will permit safe and trusted use of the generic Ticaloguard® when treating it in the same manner as Brilique®. Testing generic drug effects rather than simple bioequivalency, especially for drugs that are used in critical life-threatening situations, is crucial. We advocate applying this form of a clinical trial to test surrogate clinical efficacy for generics used in critical indications before having real-world data whenever possible.
Safety and efficacy of ticagrelor monotherapy according to drug-eluting stent type: the TWILIGHT-STENT study. [2023]In the TWILIGHT trial, ticagrelor monotherapy after a short course of dual antiplatelet therapy (DAPT) was shown to be a safe bleeding avoidance strategy in high-risk patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES).
Efficacy and Safety of Ticagrelor Monotherapy in Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis. [2021]Dual antiplatelet therapy (DAPT) and subsequent P2Y12 inhibitor monotherapy, particularly ticagrelor, is an emerging treatment strategy in patients undergoing percutaneous coronary intervention (PCI). This meta-analysis was designed to investigate whether short-term DAPT followed by ticagrelor monotherapy is associated with a favorable outcome as compared with standard DAPT (1-3 months of DAPT was termed "short-term" DAPT, 6-12 months DAPT was termed "standard" DAPT). The primary outcome was the composite of major adverse cardiovascular events (MACE) comprising myocardial infarction, stroke, and cardiovascular death. Secondary outcomes included all-cause mortality and net adverse clinical events (NACE; myocardial infarction, stroke, all-cause death, stent thrombosis, and major bleeding). The primary safety outcome was major bleeding. Three studies comprising 26,143 patients were included. The risk of MACE was similar between the two treatment groups (risk ratio (RR) 0.86, 95% confidence interval (CI), 0.72-1.02, P = 0.08, I2  = 22%). Short-term DAPT followed by ticagrelor monotherapy resulted in a 20% relative risk reduction of all-cause mortality (RR 0.80, 95% CI, 0.65-0.98, P = 0.03, I2  = 0%) and an 18% relative risk reduction of NACE (RR 0.82, 95% CI, 0.71-0.94, P = 0.005, I2  = 33%) as compared with standard DAPT. Short-term DAPT followed by ticagrelor monotherapy significantly decreased the risk of major bleeding (RR 0.67, 95% CI, 0.49-0.92, P = 0.01, I2  = 65%). In patients with acute coronary syndrome, short-term DAPT followed by ticagrelor monotherapy resulted in an unchanged ischemic risk but a significantly lower bleeding risk compared with standard DAPT. Short-term DAPT followed by ticagrelor monotherapy compared with standard DAPT resulted in a favorable safety and efficacy profile. Direct comparisons of aspirin vs. ticagrelor monotherapy following PCI are needed.
Pharmacokinetics and pharmacodynamics of ticagrelor in the treatment of cardiac ischemia. [2018]After acute coronary syndromes (ACS), the so-called dual antiplatelet therapy (DAPT), which usually consists of low-dose of aspirin in combination with a thienopyridine (clopidogrel, prasugrel) or with a cyclopentyltriazolopyrimidine (ticagrelor), reduces the risk of ischemic events. Ticagrelor, un particular, is an effective drug as it isn' a prodrug, doesn't require metabolic activation and demonstrates a rapid onset and faster offset of action. Areas covered: This article evaluates the pharmacokinetics, efficacy, safety and tolerability of ticagrelor during DAPT after ACS and its potential use beyond the canonical twelve months after PCI. The review discusses studies comparing: ticagrelor and clopidogrel (DISPERSE, DISPERSE-2, PLATO, RESPOND Trial, ONSET/OFFSET Trials), ticagrelor and placebo (PEGASUS TIMI 54 Trial). Expert opinion: For ACS patients, the PLATO trial showed that ticagrelor was superior to clopidogrel in the reduction of cardiovascular death, myocardial infarction and stroke. PEGASUS TIMI 54 showed that patients in whom ischemic events and cardiovascular death outweigh the risk of life-threatening bleeding, may benefit from prolonged ticagrelor-based dual antiplatelet therapy, over 12 months. This strategy has been recently approved by the ACC/AHA guidelines. Further studies are needed to evaluate and eventually validate the role of the prolonged DAPT in patients treated with new generation stents.