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

NCT03234114 | Unknown Phase 4 DMC

• 1 other identifier: 007
• Study Type: interventional
• Target: 3,746
• Locations: 1 country
• Sites: 1

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)

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Primary endpoint of OPTIMA-3

  A composite of cardiovascular death, myocardial infarction, ischemic stroke, systemic thromboembolism and unplanned revascularization

  Up to 12 months (± 7 days) after inclusion

• Primary safety endpoint of OPTIMA-4

  ISTH major bleeding or CRNMB

  Up to 12 months (± 7 days) after inclusion

• Primary efficacy endpoint of OPTIMA-4

  A composite of cardiovascular death, myocardial infarction, ischemic stroke, systemic thromboembolism and unplanned revascularization

  Up to 12 months (± 7 days) after inclusion

Secondary Outcomes (2)

• Major secondary endpoint of OPTIMA-3

  Up to 12 months (± 7 days) after inclusion

• Other secondary endpoints of OPTIMA-3/4

  Up to 12 months (± 7 days) after inclusion

Other Outcomes (4)

• Adenosine diphosphate (ADP, final concentration 5 μmol/L) induced platelet aggregation (PLADP)

  The venous blood will be collected at 7:30 a.m. on the day of discharge and tested within 2 hours.

• Arachidonic acid (AA, final concentration 1 mmol/L) induced platelet aggregation (PLAA)

  The venous blood will be collected at 7:30 a.m. on the day of discharge and tested within 2 hours.

• Trough concentration of dabigatran (Cmin)

  The venous blood will be collected at 0.5 hour before dosing after the patients taking at least 3 days of dabigatran and detected after stored below -80℃ for at most 2 months.

Study Arms (4)

1-month TAT

EXPERIMENTAL

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

Drug: Triple antithrombotic therapy

6-month TAT

EXPERIMENTAL

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

Drug: Triple antithrombotic therapy

12-month DAT-1

EXPERIMENTAL

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

Drug: Dual antithrombotc therapy-1

12-month DAT-2

EXPERIMENTAL

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-2

Interventions

Triple antithrombotic therapy 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)

Also known as: TAT

1-month TAT; 6-month TAT

Dual antithrombotc therapy-1 DRUG

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

Also known as: DAT-1

12-month DAT-1

Dual antithrombotc therapy-2 DRUG

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

Also known as: DAT-2

12-month DAT-2

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210029, China

RECRUITING

MeSH Terms

Conditions

Acute Coronary Syndrome

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Study Officials

• Chunjian Li, Dr, PhD

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chunjian Li, Dr, PhD

CONTACT

+86-13701465229; drcjli@hotmail.com

Xiaoxuan Gong, MD

CONTACT

+86-18851727059; xiaoxuangong@sina.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr., MD, Ph.D, Director of CCU Ward

Study Record Dates

• First Submitted: July 25, 2017
• First Posted: July 31, 2017
• Study Start: February 3, 2018
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: April 24, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)