Clinical trial NCT03431142: Optimal antiPlatelet Therapy for High Bleeding and Ischemic RISK Patients Trial
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Prolonged DAPT in ACS Patients With Hisk of Both Ischemic and Hemorrhage
Lead sponsor: Shenyang Northern Hospital
Sponsor class: OTHER
First posted: 2018-02-13
Enrollment: 7700
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical relevant bleeding events
timeFrame: During 9-month follow up
Secondary outcomes:
measure: All bleeding events
timeFrame: During 9-month follow up
measure: Major adverse cardiovascular and cerebrovascular events(MACCE)
timeFrame: During 9-month follow up
Other outcomes:
Locations:
city: Shenyang
country: China
facility: General Hospital of Shenyang Military Region
state: Liaoning
Study officials:
References:
citation: 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.