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

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

Tracking Information
First Submitted Date  ICMJE July 25, 2017
First Posted Date  ICMJE July 31, 2017
Last Update Posted Date August 24, 2020
Actual Study Start Date  ICMJE February 3, 2018
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 20, 2020)
  • 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
  • Primary safety endpoint of OPTIMA-4 [ Time Frame: Up to 12 months (± 7 days) after inclusion ]
    ISTH major bleeding or CRNMB
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: July 26, 2017)
incidence of all-cause death, non-fatal myocardial infarction, ischemic stroke, major bleeding (BARC criteria ≥ 3a) from baseline to 12 months(± 30 days) after PCI [ Time Frame: from baseline to 12 months (± 30 days) after PCI ]
including all-cause death, non-fatal myocardial infarction, ischemic stroke, major bleeding (BARC criteria ≥ 3a)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2020)
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2017)
incidence of stent thrombosis (ST), target vessel revascularization (TVR), re-hospitalization and minor bleeding from baseline to 12 months(± 30 days) after PCI [ Time Frame: from baseline to 12 months (± 30 days) after PCI ]
stent thrombosis (ST), target vessel revascularization (TVR), re-hospitalization and minor bleeding
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Optimal Antithrombotic Therapy for ACS Patients Concomitant With AF and Implanted With New-generation DES (OPTIMA-3, 4)
Official Title  ICMJE 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)
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Coronary Syndrome (ACS)
  • Non-valvular Atrial Fibrillation (NVAF)
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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
    Intervention: Drug: Triple antithrombotic therapy
  • 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
    Intervention: Drug: Triple antithrombotic therapy
  • 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
    Intervention: Drug: Dual antithrombotc therapy
  • 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
    Intervention: Drug: Dual antithrombotc therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 7, 2020)
3746
Original Estimated Enrollment  ICMJE
 (submitted: July 26, 2017)
930
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Chunjian Li, Dr, PhD +86-13701465229 drcjli@hotmail.com
Contact: Xiaoxuan Gong, MD +86-18851727059 xiaoxuangong@sina.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03234114
Other Study ID Numbers  ICMJE 007
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Chunjian Li, The First Affiliated Hospital with Nanjing Medical University
Study Sponsor  ICMJE The First Affiliated Hospital with Nanjing Medical University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Chunjian Li, Dr, PhD The First Affiliated Hospital with Nanjing Medical University
PRS Account The First Affiliated Hospital with Nanjing Medical University
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP