Optimal Antithrombotic Therapy for ACS Patients Concomitant With AF and Implanted With New-generation DES (OPTIMA-3, 4)

NCT ID: NCT03234114

Last Updated: 2023-04-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 3746 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-03
• Study Completion Date: 2024-12-31

Brief Summary

It is a multi-center randomized clinical trial (RCT) which will enroll 3746 patients with acute coronary syndrome (ACS) concomitant non-valvular atrial fibrillation (NVAF) and undergoing new generation drug eluting stent (DES) implantation at 70 centers nationwide in China and contains two sub-studies.

In the OPTIMA-3 sub-study, 2274 subjects who choose warfarin as anticoagulant will randomly receive triple antithrombotic therapy (warfarin with targeted INR 2.0-3.0, clopidogrel 75 mg od and aspirin 100 mg od) for 1 month or 6 months in a 1:1 ratio then quit aspirin till 12 months after percutaneous coronary intervention (PCI). The primary endpoint of the OPTIMA-3 is a composite of cardiovascular death, myocardial infarction, ischemic stroke, systemic thromboembolism and unplanned revascularization up to 12 months; the major secondary endpoint is the International Society of Thrombosis and Hemostasis (ISTH) major bleeding or clinically relevant non-major bleeding (CRNMB).

In the OPTIMA-4 sub-study, 1472 subjects who prefer dabigatran will be randomly assigned in a 1:1 ratio to a dual antithrombotic therapy of dabigatran 110 mg twice daily with ticagrelor 90 mg twice daily or with clopidogrel 75 mg od for 12 months after PCI. The primary safety endpoint of the OPTIMA-4 is ISTH major bleeding or CRNMB at 12 months; the primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, ischemic stroke, systemic thromboembolism and unplanned revascularization.

Other secondary endpoints comprise death (cardiovascular, non- cardiovascular), MI (fatal or non-fatal, Q-wave or non-Q-wave), unplanned revascularization (target or non-target vessel, target or non-target lesion), stent thrombosis (possible, probable, definite), stroke (hemorrhage or ischemic), all bleeding (ISTH and BARC criteria) and net adverse events.

All endpoints will be collected and compared between subgroups and sub-studies during hospitalization and in 1 month (± 7 days), 6 months (± 7 days) and 12 months (± 7 days) for office visits and in 2 weeks (± 7 days), 2 months (± 7 days) and 3 months (± 7 days) for phone call visits.

Conditions

Acute Coronary Syndrome (ACS); Non-valvular Atrial Fibrillation (NVAF)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1-month TAT

Randomized experimental group in the OPTIMA-3 substudy; Triple antithrombotic therapy (warfarin with targeted INR 2.0-3.0, clopidogrel 75 mg q.d. and aspirin 100 mg q.d.) for 1 month (30 days) then quit aspirin till 12 months after PCI

Group Type: EXPERIMENTAL

Triple antithrombotic therapy

Intervention Type: DRUG

Including warfarin with targeted INR 2.0-3.0 (Shanghai Xinyi pharma co., LTD, China), aspirin 100 mg q.d. (Bayer, Germany) and clopidogrel 75 mg q.d. (Sanofi, France)

6-month TAT

Randomized control group in the OPTIMA-3 substudy; Triple antithrombotic therapy (warfarin with targeted INR 2.0-3.0, clopidogrel 75 mg q.d. and aspirin 100 mg q.d.) for 6 months (180 days）then quit aspirin till 12 months after PCI

Group Type: EXPERIMENTAL

Triple antithrombotic therapy

Intervention Type: DRUG

Including warfarin with targeted INR 2.0-3.0 (Shanghai Xinyi pharma co., LTD, China), aspirin 100 mg q.d. (Bayer, Germany) and clopidogrel 75 mg q.d. (Sanofi, France)

12-month DAT-1

Randomized experimental group in the OPTIMA-4 substudy; Dual antithrombotic therapy including dabigatran 110 mg b.i.d. with clopidogrel 75 mg q.d. for 12 months after PCI

Group Type: EXPERIMENTAL

Dual antithrombotc therapy-1

Intervention Type: DRUG

Including dabigatran 110 mg b.i.d. (Boehringer Ingelheim, Germany) plus clopidogrel 75 mg q.d. (Sanofi, France)

12-month DAT-2

Randomized control group in the OPTIMA-4 substudy; Dual antithrombotic therapy including dabigatran 110 mg b.i.d. with ticagrelor 90 mg b.i.d for 12 months after PCI

Group Type: EXPERIMENTAL

Dual antithrombotc therapy-2

Intervention Type: DRUG

Including dabigatran 110 mg b.i.d. (Boehringer Ingelheim, Germany) plus ticagrelor 90 mg b.i.d. (AstraZeneca, Britain)

Interventions

Triple antithrombotic therapy

Including warfarin with targeted INR 2.0-3.0 (Shanghai Xinyi pharma co., LTD, China), aspirin 100 mg q.d. (Bayer, Germany) and clopidogrel 75 mg q.d. (Sanofi, France)

Intervention Type: DRUG

Dual antithrombotc therapy-1

Including dabigatran 110 mg b.i.d. (Boehringer Ingelheim, Germany) plus clopidogrel 75 mg q.d. (Sanofi, France)

Intervention Type: DRUG

Dual antithrombotc therapy-2

Including dabigatran 110 mg b.i.d. (Boehringer Ingelheim, Germany) plus ticagrelor 90 mg b.i.d. (AstraZeneca, Britain)

Intervention Type: DRUG

Other Intervention Names

TAT; DAT-1; DAT-2

Eligibility Criteria

Inclusion Criteria

• ≥ 18 years;
• ACS patients concomitant non-valvular AF (paroxysmal, persistent and permanent) underwent PCI and new-generation DES implantation;
• CHA2DS2-VASc score ≥ 2;
• Acceptable risk of bleeding at the discretion of the researchers (e.g. HAS-BLED score ≤ 2)
• Consent to participate in the trial

Exclusion Criteria

• DES implanted in the left main coronary artery
• Cardiogenic shock or Killip III-IV
• STEMI patients with malignant arrhythmias or underwent electrodefibrillation or CPR or with cardiac mechanical complications (heart rupture, ventricular septal perforation, nipple muscle fracture, etc.)
• History of gastrointestinal or intracranial hemorrhage; active bleeding, trauma or major surgery within one month; suspected or diagnosed aortic dissection
• Ischemic stroke with limb dysfunction or dysphasia
• Known allergy or intolerance to the study medications: warfarin, clopidogrel, aspirin, dabigatran, ticagrelor and heparin
• Participating in other ongoing trials
• Planned surgery in 12 months requiring to withdraw the antiplatelet agents
• Planned RFCA or left atrial appendage occlusion in the next 12m
• Abnormal liver or kidney function (ALT ≥ 3 ULN; estimated CrCl < 30 ml/min calculated by Cockcroft-Gault equation); diagnosed liver cirrhosis
• Hematological disease with bleeding tendency; hemoglobin < 100 g/L, platelet count < 100 × 10^9 /L
• Malignancies or life expectancy less than 1 year
• Pregnant (present, suspected, or planned) or lactating woman
• Patients who are taking drugs which may interact with study agents, such as miconazole, ketoconazole, fluconazole, voriconazole, itraconazole, posaconazole, efinaconazole, and rifampicin, etc.
• Patients with any other conditions that may not be suitable to participate in the trial at the discretion of the researchers.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Chunjian Li

Dr., MD, Ph.D, Director of CCU Ward

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Chunjian Li, Dr, PhD

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital with Nanjing Medical University

Locations

First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Chunjian Li, Dr, PhD

Role: CONTACT

drcjli@hotmail.com

+86-13701465229

Xiaoxuan Gong, MD

Role: CONTACT

xiaoxuangong@sina.com

+86-18851727059

Facility Contacts

Fuming Zhang, M.D.

Role: primary

jsphkj@163.com

+86-25-83718836 ext. 6360

Yi Chai, M.D.

Role: backup

jsphkj@163.com

+86-25-83718836 ext. 6360

Other Identifiers

007

Identifier Type: -

Identifier Source: org_study_id