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

Primary Purpose

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

Status
Recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Triple antithrombotic therapy
Dual antithrombotc therapy-1
Dual antithrombotc therapy-2
Sponsored by
The First Affiliated Hospital with Nanjing Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Coronary Syndrome (ACS) focused on measuring new generation drug eluting stent (DES), antithrombotic therapy, randomized clinical trial (RCT)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • First Affiliated Hospital of Nanjing Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

1-month TAT

6-month TAT

12-month DAT-1

12-month DAT-2

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

Primary endpoint of OPTIMA-3
A composite of cardiovascular death, myocardial infarction, ischemic stroke, systemic thromboembolism and unplanned revascularization
Primary safety endpoint of OPTIMA-4
ISTH major bleeding or CRNMB
Primary efficacy endpoint of OPTIMA-4
A composite of cardiovascular death, myocardial infarction, ischemic stroke, systemic thromboembolism and unplanned revascularization

Secondary Outcome Measures

Major secondary endpoint of OPTIMA-3
Major bleeding or clinically relevant non-major bleeding assessed by the ISTH definition
Other secondary endpoints of OPTIMA-3/4
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

Full Information

First Posted
July 25, 2017
Last Updated
April 20, 2023
Sponsor
The First Affiliated Hospital with Nanjing Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT03234114
Brief Title
Optimal Antithrombotic Therapy for ACS Patients Concomitant With AF and Implanted With New-generation DES (OPTIMA-3, 4)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 3, 2018 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The First Affiliated Hospital with Nanjing Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Coronary Syndrome (ACS), Non-valvular Atrial Fibrillation (NVAF)
Keywords
new generation drug eluting stent (DES), antithrombotic therapy, randomized clinical trial (RCT)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3746 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1-month TAT
Arm Type
Experimental
Arm Description
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
Arm Title
6-month TAT
Arm Type
Experimental
Arm Description
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
Arm Title
12-month DAT-1
Arm Type
Experimental
Arm Description
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
Arm Title
12-month DAT-2
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Triple antithrombotic therapy
Other Intervention Name(s)
TAT
Intervention Description
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
Intervention Name(s)
Dual antithrombotc therapy-1
Other Intervention Name(s)
DAT-1
Intervention Description
Including dabigatran 110 mg b.i.d. (Boehringer Ingelheim, Germany) plus clopidogrel 75 mg q.d. (Sanofi, France)
Intervention Type
Drug
Intervention Name(s)
Dual antithrombotc therapy-2
Other Intervention Name(s)
DAT-2
Intervention Description
Including dabigatran 110 mg b.i.d. (Boehringer Ingelheim, Germany) plus ticagrelor 90 mg b.i.d. (AstraZeneca, Britain)
Primary Outcome Measure Information:
Title
Primary endpoint of OPTIMA-3
Description
A composite of cardiovascular death, myocardial infarction, ischemic stroke, systemic thromboembolism and unplanned revascularization
Time Frame
Up to 12 months (± 7 days) after inclusion
Title
Primary safety endpoint of OPTIMA-4
Description
ISTH major bleeding or CRNMB
Time Frame
Up to 12 months (± 7 days) after inclusion
Title
Primary efficacy endpoint of OPTIMA-4
Description
A composite of cardiovascular death, myocardial infarction, ischemic stroke, systemic thromboembolism and unplanned revascularization
Time Frame
Up to 12 months (± 7 days) after inclusion
Secondary Outcome Measure Information:
Title
Major secondary endpoint of OPTIMA-3
Description
Major bleeding or clinically relevant non-major bleeding assessed by the ISTH definition
Time Frame
Up to 12 months (± 7 days) after inclusion
Title
Other secondary endpoints of OPTIMA-3/4
Description
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
Time Frame
Up to 12 months (± 7 days) after inclusion
Other Pre-specified Outcome Measures:
Title
Adenosine diphosphate (ADP, final concentration 5 μmol/L) induced platelet aggregation (PLADP)
Description
The PLADP will be detected by light transmission aggregometry (LTA) to reflect platelet function under the treatment of clopidogrel or ticagrelor.
Time Frame
The venous blood will be collected at 7:30 a.m. on the day of discharge and tested within 2 hours.
Title
Arachidonic acid (AA, final concentration 1 mmol/L) induced platelet aggregation (PLAA)
Description
The PLAA will be detected by light transmission aggregometry (LTA) to reflect platelet function under the treatment of aspirin.
Time Frame
The venous blood will be collected at 7:30 a.m. on the day of discharge and tested within 2 hours.
Title
Trough concentration of dabigatran (Cmin)
Description
The trough concentration of dabigatran (Cmin) of dabigatran is to be detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) in OPTIMA-4 trial.
Time Frame
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.
Title
Single nucleotide polymorphisms (SNPs)
Description
The single nucleotide polymorphisms (SNPs) related to the antithrombotic agents used in different groups will be detected as follows: (1) clopidogrel-related SNPs: CYP2C19 (rs12248560, rs28399504, rs41291556, rs4244285, rs4986893, rs5633701, rs72552267, rs72558186); (2) ticagrelor-related SNPs: SLCO1B1 (rs113681054), OATP1B1 (rs4149056), CYP3A4 (rs62471956, rs56324128), UGT2B7 (rs61361928); (3) dabigatran-related SNP: ABCB1 (rs4148738, rs1045642), CES1 (rs8192935).
Time Frame
The venous blood will be collected at any time during hospitalization and detected after stored below -80℃ for at most 5 years.

10. Eligibility

Sex
All
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chunjian Li, Dr, PhD
Phone
+86-13701465229
Email
drcjli@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaoxuan Gong, MD
Phone
+86-18851727059
Email
xiaoxuangong@sina.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chunjian Li, Dr, PhD
Organizational Affiliation
The First Affiliated Hospital with Nanjing Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
First Affiliated Hospital of Nanjing Medical University
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fuming Zhang, M.D.
Phone
+86-25-83718836
Ext
6360
Email
jsphkj@163.com
First Name & Middle Initial & Last Name & Degree
Yi Chai, M.D.
Phone
+86-25-83718836
Ext
6360
Email
jsphkj@163.com
First Name & Middle Initial & Last Name & Degree
Chunjian Li, Ph.D
First Name & Middle Initial & Last Name & Degree
Xiaoxuan Gong, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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