Optimal antiPlatelet Therapy for High Bleeding and Ischemic RISK Patients Trial (OPT-BIRISK)

Extended Antiplatelet Therapy With Clopidogrel Alone Versus Clopidogrel Plus Aspirin After Completion of 9- to 12-month Dual Antiplatelet Therapy for ACS Patients With Both High Bleeding and Ischemic Risk.

Current guidelines recommend that patients with ACS undergoing stent implantation might be offered extended DAPT treatment for up to 30 months if necessary.

Therefore, we designed a prospective, multicenter, randomized, placebo-controlled trial among ACS patients with high-risk on ischemic and bleeding who received a new generation of DES and received 9 to 12 months of DAPT, and evaluated whether clopidogrel monotherapy reduce the risk of bleeding compared with clopidogrel plus ASA in the following 9 months and achieved non-inferior outcomes in preventing ischemic risk.

Study Overview

• Status: Unknown
• Conditions: Prolonged DAPT in ACS Patients With Hisk of Both Ischemic and Hemorrhage
• Intervention / Treatment: Drug: Clopidogrel; Drug: Clopidogrel+aspirin

Detailed Description

Current guidelines recommend that patients with ACS undergoing stent implantation might be offered extended DAPT treatment for up to 30 months if necessary. For patients with high risk of both ischemic and hemorrhage, despite prolonged use of DAPT may bring antithrombotic benefit, it may also increase the risk of bleeding. There is an urgent need for specific guiding on intensive antiplatelet therapy in this population of patients to reduce the risk of ischemia and to avoid the risk of bleeding.

Previous studies have shown that, after 12 months of DAPT treatment, continuation of clopidogrel monotherapy may further reduce the risk of ischemia and bleeding compared with aspirin. Therefore, we designed a prospective, multicenter, randomized, placebo-controlled trial among ACS patients with high-risk on ischemic and bleeding who received a new generation of DES and received 9 to 12 months of DAPT, and evaluated whether clopidogrel monotherapy reduce the risk of bleeding compared with clopidogrel plus ASA in the following 9 months and achieved non-inferior outcomes in preventing ischemic risk.

• Study Type: Interventional
• Enrollment (Anticipated): 7700
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110016
      • Recruiting
      • General Hospital of Shenyang Military Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ACS patients undergoing PCI (New-Generation DES) and finishing 9-12 months of DAPT
• 18 ~ 85 years old adult patients
• Patients under the age of 65 must meet at least one of the following clinical criteria of high bleeding risk and at least one of the following clinical criteria of high ischemic risk; Patients aged 65-75 must meet one of the following clinical criteria of either high bleeding risk or high ischemic risk.

Clinical criteria of high bleeding risk:

• ≥75 years old
• female
• Iron deficiency anemia
• history of stroke (hemorrhagic or ischemic)
• ongoing medical treatment of diabetes (oral hypoglycemic agents or subcutaneous insulin)
• Chronic kidney disease (eGFR <60mL/min or creatinine clearance<60mL/min)

Clinical criteria of high ischemic risk:

• ≥75 years old
• Multiple coronary lesions
• target lesions required for stent of total length> 30mm
• Thrombotic target lesions
• Bifurcation lesions are Medina 0, 1, 1 or 1, 1, and 1, with stents implanted in both main branch and side branch
• Left main coronary artery (≥50%) or proximal LAD (≥70%) lesions
• Calcified plaques requiring endovascular excision
• acute coronary syndrome with troponin positive
• Previous myocardial infarction, ischemic stroke, diagnosed peripheral arterial disease (PAD), or revascularization due to coronary artery disease (CAD) / PAD
• recurrent myocardial infarction, revascularization, stent thrombosis, stroke in the last 9 months
• ongoing medical treatment of diabetes (oral hypoglycemic agents or subcutaneous insulin)
• Chronic kidney disease (eGFR<60 mL/min or creatinine clearance <60 mL/min)

Exclusion Criteria:

• Discontinuation or termination of DAPT treatment during the past 6 months due to adverse events (bleeding or ischemia) or other conditions
• Surgery plan within 90 days
• Coronary Revascularization (Surgical or Intervention) Program within 90 days
• Dialysis-dependent renal failure
• Moderate or severe hepatic insufficiency (2 times the upper limit of normal for ALT or AST)
• Life expectancy <1 year
• Unable or unwilling to provide informed consent
• Women with childbearing potential
• Platelet count <100000/mm3
• Subjects undergoing warfarin or similar anticoagulant therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Clopidogrel monotherapy; On the basis of 9-12 months of DAPT(aspirin+clopidogrel), continue clopidogrel monotherapy in the following 9 months.	Drug: Clopidogrel; Additional 9 months of clopidogrel monotherapy after 9-12 months of DAPT (aspirin+clopidogrel)
ACTIVE_COMPARATOR: Clopidogrel plus aspirin; On the basis of 9-12 months of DAPT(aspirin+clopidogrel), continue DAPT (aspirin+clopidogrel) in the following 9 months.	Drug: Clopidogrel+aspirin; Additional 9 months of clopidogrel plus aspirin after 9-12 months of DAPT (aspirin+clopidogrel)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical relevant bleeding events	defined as BARC type 2-5 bleeding events	During 9-month follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All bleeding events	defined all BARC type 1-5 bleeding events	During 9-month follow up
Major adverse cardiovascular and cerebrovascular events(MACCE)	defined as a composite endpoints of all-cause death, myofarction, stroke and clinically indicated revascularization	During 9-month follow up

Collaborators and Investigators

• Sponsor: Shenyang Northern Hospital

Publications and helpful links

General Publications

• Li Y, Jing Q, Wang B, Wang X, Li J, Qiao S, Chen S, Angiolillo DJ, Han Y. Extended antiplatelet therapy with clopidogrel alone versus clopidogrel plus aspirin after completion of 9- to 12-month dual antiplatelet therapy for acute coronary syndrome patients with both high bleeding and ischemic risk. Rationale and design of the OPT-BIRISK double-blinded, placebo-controlled randomized trial. Am Heart J. 2020 Oct;228:1-7. doi: 10.1016/j.ahj.2020.07.005. Epub 2020 Jul 9.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 12, 2018
• Primary Completion (ANTICIPATED): September 30, 2021
• Study Completion (ANTICIPATED): September 30, 2021

Study Registration Dates

• First Submitted: February 7, 2018
• First Submitted That Met QC Criteria: February 7, 2018
• First Posted (ACTUAL): February 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 15, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia; Hemorrhage; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Clopidogrel
• Other Study ID Numbers: CLOPIL08732

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No