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

• ClinicalTrials.gov Identifier: NCT03234114
• Recruitment Status: Recruiting
• First Posted: July 31, 2017
• Last Update Posted: August 24, 2020
• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Information provided by (Responsible Party): Chunjian Li, The First Affiliated Hospital with Nanjing Medical University

Study Description

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 OPTIMAL-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 OPTIMAL-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.

Condition or disease	Intervention/treatment	Phase
Acute Coronary Syndrome (ACS); Non-valvular Atrial Fibrillation (NVAF)	Drug: Triple antithrombotic therapy; Drug: Dual antithrombotc therapy	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 3746 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Optimal Antithrombotic Therapy for Acute Coronary Syndrome Patients Concomitant With Atrial Fibrillation and Implanted With New-generation Drug-eluting Stent: OPTImal Management of Antithrombotic Agents (OPTIMA-3, 4)
• Actual Study Start Date: February 3, 2018
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1-month TT; Randomized experimental group in the OPTIMA-3 substudy; Triple antithrombotic therapy (warfarin with targeted INR 2.0-3.0, clopidogrel 75 mg od and aspirin 100 mg od) for 1 month (30 days) then quit aspirin till 12 months after PCI	Drug: Triple antithrombotic therapy; Including warfarin with targeted INR 2.0-3.0 (Shanghai Xinyi pharma co., LTD, China), aspirin 100 mg per day (Bayer, Germany) and clopidogrel 75 mg per day (Sanofi, France); Other Name: TT
Experimental: 6-month TT; Randomized control group in the OPTIMA-3 substudy; Triple antithrombotic therapy (warfarin with targeted INR 2.0-3.0, clopidogrel 75 mg od and aspirin 100 mg od) for 6 months (180 days）then quit aspirin till 12 months after PCI	Drug: Triple antithrombotic therapy; Including warfarin with targeted INR 2.0-3.0 (Shanghai Xinyi pharma co., LTD, China), aspirin 100 mg per day (Bayer, Germany) and clopidogrel 75 mg per day (Sanofi, France); Other Name: TT
Experimental: 12-month DT-1; Randomized experimental group in the OPTIMA-4 substudy; Dual antithrombotic therapy including dabigatran 110 mg b.i.d. with clopidogrel 75 mg qd for 12 months after PCI	Drug: Dual antithrombotc therapy; Including dabigatran 110 mg b.i.d. (Boehringer Ingelheim, Germany) plus ticagrelor 90 mg b.i.d. (AstraZeneca, Britain) or clopidogrel 75 mg per day (Sanofi, France); Other Name: DT
Experimental: 12-month DT-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	Drug: Dual antithrombotc therapy; Including dabigatran 110 mg b.i.d. (Boehringer Ingelheim, Germany) plus ticagrelor 90 mg b.i.d. (AstraZeneca, Britain) or clopidogrel 75 mg per day (Sanofi, France); Other Name: DT

Outcome Measures

Primary Outcome Measures :

1. Primary endpoint of OPTIMA-3 [ Time Frame: Up to 12 months (± 7 days) after inclusion ]
   A composite of cardiovascular death, myocardial infarction, ischemic stroke, systemic thromboembolism and unplanned revascularization
2. Primary safety endpoint of OPTIMA-4 [ Time Frame: Up to 12 months (± 7 days) after inclusion ]
   ISTH major bleeding or CRNMB
3. Primary efficacy endpoint of OPTIMA-4 [ Time Frame: Up to 12 months (± 7 days) after inclusion ]
   A composite of cardiovascular death, myocardial infarction, ischemic stroke, systemic thromboembolism and unplanned revascularization

Secondary Outcome Measures :

1. Major secondary endpoint of OPTIMA-3 [ Time Frame: Up to 12 months (± 7 days) after inclusion ]
   Major bleeding or clinically relevant non-major bleeding assessed by the ISTH definition
2. Other secondary endpoints of OPTIMA-3/4 [ Time Frame: Up to 12 months (± 7 days) after inclusion ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Chunjian Li, Dr, PhD; +86-13701465229; drcjli@hotmail.com

Contact: Xiaoxuan Gong, MD; +86-18851727059; xiaoxuangong@sina.com

Locations

China, Jiangsu

First Affiliated Hospital of Nanjing Medical University; Recruiting

Nanjing, Jiangsu, China, 210029

Contact: Fuming Zhang, M.D. +86-25-83718836 ext 6360 jsphkj@163.com

Contact: Yi Chai, M.D. +86-25-83718836 ext 6360 jsphkj@163.com

Principal Investigator: Chunjian Li, Ph.D

Sub-Investigator: Xiaoxuan Gong, MD

Sponsors and Collaborators

The First Affiliated Hospital with Nanjing Medical University

Investigators

• Principal Investigator: Chunjian Li, Dr, PhD; The First Affiliated Hospital with Nanjing Medical University

More Information

• Responsible Party: Chunjian Li, Dr., MD, Ph.D, Director of CCU Ward, The First Affiliated Hospital with Nanjing Medical University
• ClinicalTrials.gov Identifier: NCT03234114
• Other Study ID Numbers: 007
• First Posted: July 31, 2017
• Last Update Posted: August 24, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Chunjian Li, The First Affiliated Hospital with Nanjing Medical University:

new generation drug eluting stent (DES); antithrombotic therapy; randomized clinical trial (RCT)

Additional relevant MeSH terms:

Atrial Fibrillation; Acute Coronary Syndrome; Syndrome; Disease; Pathologic Processes; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Myocardial Ischemia; Vascular Diseases