P2Y12 Inhibitor Monotherapy Versus Extended DAPT in Patients Treated With Bioresorbable Scaffold (SMART-CHOICEII)

SMart Angioplasty Research Team: Comparison Between P2Y12 Inhibitor MonotHerapy and Dual Antiplatelet Therapy in Patients UndergOing Implantation of Coronary BiorEsorbable Scaffold II: (SMART-CHOICE II) Trial

This study aimed to compare the efficacy and safety of P2Y12 inhibitor monotherapy versus extended dual antiplatelet therapy (DAPT) following 12-month of DAPT in patients undergoing percutaneous coronary intervention (PCI) with bioresorbable scaffold (BRS)

Study Overview

• Status: Terminated
• Conditions: Coronary Artery Disease; Atherosclerosis; Stents
• Intervention / Treatment: Drug: Clopidogrel; Drug: Ticagrelor; Drug: Aspirin

Detailed Description

After the development of second generation drug-eluting stent (DES), clinical outcomes including in-stent restenosis have been dramatically improved in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) compared with bare metal stent or first generation DES era. However, interventional cardiologist still concern about late adverse cardiac events including stent thrombosis (ST) in patients who received implantation of permanent metallic stent. Bioresorbable scaffold (BRS) have been developed to provide mechanical support and drug-delivery function similar to those of DES for approximately 1 year, followed by complete bioresorption over several years. It has the advantages of reducing the risk of late ST and maintaining of normal vascular function because these novel devices are expected to leave no permanent materials within the vessel. Although there was no significant difference from previous randomized controlled studies for evaluating the clinical outcomes at 1-year between BRS and DES, recently documented ARSORB II trial, which compared 3-year outcomes between BRS and DES, show that patients treated with BRS had a higher risk of device-oriented composite endpoint mainly driven by target vessel myocardial infarction (MI) compared to those with DES. In addition, in several case reports, the late ST after discontinuation of dual anti-platelet therapy (DAPT) was reported in patients who underwent BRS implantation. Therefore, the efficacy of extended DAPT and needs for optimal DAPT duration in patients treated with BRS have been emerged. In the DAPT study, randomized controlled trial including approximately 10,000 patients, DAPT beyond 1 year after placement of a DES, as compared with aspirin therapy alone, significantly reduced the risks of major adverse cardiovascular and cerebrovascular events (MACCE) and ST. However, extend use of DAPT increases bleeding risk and cost. Endoscopic, dental, and surgical procedures are often delayed due to extended DAPT, which may affect the patient's quality of life. In addition, there was no significant difference in all-cause mortality between extended DAPT and aspirin monotherapy in the DAPT study because of increased bleeding risk in extended DAPT group. Therefore, to determine the optimal or minimal necessary duration of DAPT is very important. The other important issue is that which antiplatelet agent is more appropriate after DAPT. In CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events) trial, clopidogrel showed a superior efficacy in preventing ischemic events compared with aspirin and the incidence of gastrointestinal bleeding was significantly lower with clopidogrel than with aspirin. Moreover, clopidogrel monotherapy was associated with a reduced risk of ischemic events without increased bleeding risk compared with aspirin monotherapy in patients receiving DES after 12-month DAPT. However, current guidelines still recommend aspirin monotherapy after 6-12 months of DAPT in patients treated with DES, there were no data for evaluating the optimal duration of DAPT and preferred choice of monotherapy in patients treated with BRS. Through results of previous studies, the authors postulated that P2Y12 antagonist monotherapy, which might have superior ability to prevent ischemic event compared to aspirin monotherapy, had similar risk of ischemic events with lower risk of bleeding complication compared with extended DAPT in patients who received BRS implantation with 12-month DAPT. Therefore, in the SMART-CHOICE II trial, we will test noninferiority of P2Y12 antagonist monotherapy compared with aspirin plus P2Y12 antagonist after 12-month of DAPT in patients treated with BRS.

Stratification: presence of diabetes mellitus, clinical presentation (acute coronary syndrome), type of P2Y12 inhibitor (clopidogrel or ticagrelor), and investigational center.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject must be at least 19 years of age.
• Patients who do not occur a major adverse cardiac and cerebral events (MACCE) at 12-month after BRS implantation
• Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving P2Y12 antagonist monotherapy or aspirin plus P2Y12 antagonist and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure.

Exclusion Criteria:

• Active bleeding
• Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plan to become pregnant any time after enrollment into this study
• Non-cardiac co-morbid conditions are present with life expectancy <2 year or that may result in protocol non-compliance (per site investigator's medical judgment).

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: P2Y12 receptor inhibitor monotherapy arm; In patients who do not occur a MACCE until 12-month after BRS implantation, P2Y12 receptor inhibitor monotherapy arm will be received clopidogrel 75mg qd or ticagrelor 60mg bid during follow-up period (24 months after randomization).	Drug: Clopidogrel; 75mg/day; Other Names: Clopidogrel or its generic; Drug: Ticagrelor; 120mg/day; Other Names: Brillinta
Active Comparator: Extended DAPT arm; In patients who do not occur a MACCE until 12-month after BRS implantation, Extended DAPT arm will be received aspirin 100mg qd plus P2Y12 receptor inhibitor (clopidogrel 75mg qd or ticagrelor 60mg bid) during follow-up period (24 months after randomization).	Drug: Clopidogrel; 75mg/day; Other Names: Clopidogrel or its generic; Drug: Ticagrelor; 120mg/day; Other Names: Brillinta; Drug: Aspirin; 100mg/day; Other Names: Any commercially available aspirin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A composite of death, myocardial infarction, and cerebrovascular events	defined as MACCE	36 months after the index procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause death	Any death	36 months after the index procedure
Cardiac death	ARC definition	36 months after the index procedure
Myocardial infarction	ARC definition	36 months after the index procedure
Cerebrovascular accident	ischemic and hemorrhagic	36 months after the index procedure
target lesion revascularization (TLR)	ischemic driven or all	36 months after the index procedure
Target vessel revascularization (TVR)	ischemic driven or all	36 months after the index procedure
Any revascularization	ischemic driven or all	36 months after the index procedure
Stent thrombosis (ST)	definite or probable ST by Academic Research Consortium (ARC) definition	36 months after the index procedure
Bleeding Academic Research Consortium (BARC) bleeding 2,3, or 5	Safety Endpoints, defined as actionable, overt, and fatal bleeding by BARC definition	36 months after the index procedure

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Study Chair: Joo-Yong Hahn, MD, PhD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2017
• Primary Completion (Actual): December 18, 2017
• Study Completion (Actual): February 9, 2018

Study Registration Dates

• First Submitted: April 1, 2017
• First Submitted That Met QC Criteria: April 13, 2017
• First Posted (Actual): April 18, 2017

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Coronary artery disease; Dual antiplatelet therapy; Bioresorbable scaffold; P2Y12 receptor inhibitor
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Atherosclerosis; 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; Ticagrelor; Clopidogrel
• Other Study ID Numbers: CHOICEII16453143

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked

Drug and device information, study documents

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