Tailored Anti-platelet Therapy After DES Implantation in High-risk Patients

A Randomized Comparison of TAILOReD Anti-Platelet Therapy According to Platelet Reactivity Versus Uniform Clopidogrel Monotherapy Beyond 12 Months After Drug-eluting Stent Implantation in High-risk Patients: TAILOR-DAPT

Clopidogrel monotherapy has been found effective in reducing ischaemic cardiovascular and haemorrhagic complications in patients with drug-eluting stent (DES) placement. However, concerns remain about the safety of long-term clopidogrel monotherapy in high-risk patients with HPR (high platelet reactivity) who do not respond adequately to clopidogrel. This study aims to evaluate the effectiveness of a patient-tailored antiplatelet therapy strategy that considers platelet aggregation in high-risk patients with DES placement beyond 12 months after stenting.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Clopidogrel monotherapy; Drug: Tailored anti-platelet therapy

Detailed Description

This study will randomly assign eligible participants who underwent drug-eluting stent placement and have maintained the standard antiplatelet therapy for 12 months to either a control group or an intervention group. The control group will continue receiving clopidogrel monotherapy for 24 months regardless of their PRU (platelet reactivity unit) values. The intervention group will receive personalized antiplatelet therapy based on their PRU values: for non-HPR patients (PRU<208), clopidogrel monotherapy will be continued; for HPR patients (PRU≥208), dual antiplatelet therapy will be prescribed based on clinical diagnosis at the time of stent implantation and individual patients' ischemic/bleeding risk profiles. Patients (≥50 years) who presented with acute myocardial infarction at the time of coronary intervention, and have high-risk characteristics (① ≥65 years ② multi-vessel disease ③ diabetes mellitus ④ chronic kidney disease ⑤ recurrent myocardial infarction) will receive ticagrelor 60 mg twice daily with aspirin, whereas the remainder will receive clopidogrel with aspirin. For high-bleeding-risk patients with two or more major bleeding risk factors according to ARC-HBR, the investigator may consider early discontinuation of dual antiplatelet therapy or de-escalation therapy like aspirin monotherapy based on the patient's risk profile. The treatment assignment ratio is 1:1. The study period will be up to 24 months from the time of randomization.

• Study Type: Interventional
• Enrollment (Estimated): 3434
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Byeong-Keuk Kim; Phone Number: 02-2228-8465; Email: kimbk@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Severance Hospital
    • Contact: Byeong-Keuk Kim; Phone Number: 02-2228-8465; Email: kimbk@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients > 18 years old
2. Patients who previously underwent percutaneous coronary intervention with drug-eluting stent implantation 12 months (± 3 months) ago.
3. At least one high risk characteristics of ischemic events

High risk patients

1. Acute coronary syndrome
2. Previous history of cerebrovascular accidents
3. Previous history of peripheral artery intervention
4. Heart failure
5. Diabetes mellitus requiring medication
6. Chronic kidney disease (regardless of requirement of renal replacement therapy)

High risk lesions

1. Left main disease
2. Multivessel disease, 2- or 3- vessels
3. Bifurcation lesions requiring 2 or more stents
4. Chronic total occlusion
5. In-stent restenosis
6. Graft lesions
7. Diffuse long lesion requiring stent(s) with total stent length ≥28 mm
8. Lesion at small sized vessel requiring stent(s) with stent diameter ≤2.5 mm
9. Calcified lesions requiring atherectomy

Exclusion Criteria:

1. Patients > 80 years old
2. Pregnant women or women with potential childbearing
3. Life expectancy < 1 year
4. Refusal or inability to understand of informed consent
5. Patients eligible to long-term anticoagulation therapy
6. Patients with major bleeding events in previous 3 months before randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Uniform Therapy; Patients will continue clopidogrel monotherapy for 24 months from randomization, irrespective of their PRU measurement.	Drug: Clopidogrel monotherapy; Patients will receive clopidogrel monotherapy (75 mg qd) for 24 months after randomization, irrespective of PRU value or bleeding risk.
Experimental: Tailored Therapy; Patients in the intervention arm will receive tailored anti-platelet therapy according to PRU and bleeding risk	Drug: Tailored anti-platelet therapy; In the tailored therapy arm, non-HPR (PRU<208) patients will continue clopidogrel monotherapy until the end of the study at 24 months from randomization, while HPR (PRU≥208) patients will receive dual anti-platelet therapy according to the clinical diagnosis at the time of drug-eluting stent placement: High-risk patients with prior myocardial infarction will receive ticagrelor 60 mg twice daily wiht aspirin 100 mg daily, while the remainder will receive clopidogrel 75 mg daily with aspirin 100 mg daily. For HBR patietns, early cessation of dual antiplatelet therapy or aspirin monotherapy could be considered at the investigator's discretion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net Clinical Adverse Clinical Events (NACE) for 24 months	A composite of all-cause of death, myocardial infarction (MI), stent thrombosis, stroke, or BARC type 2, 3, or 5 bleeding	upto 2 years after randomization

Secondary Outcome Measures

Outcome Measure	Time Frame
All-cause death	upto 2 years after randomization
Cardiovascular death	upto 2 years after randomization
Myocardial infarction	upto 2 years after randomization
Stent thrombosis	upto 2 years after randomization
Ischemia-driven target vessel revascularization	upto 2 years after randomization
Any revascularization	upto 2 years after randomization
Stroke	upto 2 years after randomization
Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding	upto 2 years after randomization
Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding	upto 2 years after randomization
Bleeding Academic Research Consortium (BARC) type 2 bleeding	upto 2 years after randomization
Bleeding Academic Research Consortium (BARC) type 3 bleeding	upto 2 years after randomization
Bleeding Academic Research Consortium (BARC) type 5 bleeding	upto 2 years after randomization
All-cause death, myocardial infarction, or stroke	upto 2 years after randomization
Cardiovascular death, myocardial infarction, stent thrombosis, or stroke	upto 2 years after randomization
All-cause death, myocardial infarction, stent thrombosis, stroke, or BARC type 3 or 5 bleeding	upto 2 years after randomization

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Byeong-Keuk Kim, Severance Cardiovascular Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2023
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: May 22, 2023
• First Submitted That Met QC Criteria: July 3, 2023
• First Posted (Actual): July 10, 2023

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 27, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Coronary artery disease; platelet reactivity; antiplatelet therapy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: 4-2023-0175

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