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

• ClinicalTrials.gov Identifier: NCT03119012
• Recruitment Status: Recruiting
• First Posted: April 18, 2017
• Last Update Posted: April 9, 2019
• Sponsor: Samsung Medical Center
• Information provided by (Responsible Party): Joo-Yong Hahn, Samsung Medical Center

Study Description

Brief Summary:

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)

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease; Stents; Atherosclerosis	Drug: Clopidogrel; Drug: Ticagrelor; Drug: Aspirin	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1520 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Prospective, open label, two-arm, randomized controlled trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: April 19, 2017
• Estimated Primary Completion Date: April 2022
• Estimated Study Completion Date: April 2022

Arms and Interventions

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 Name: Clopidogrel or its generic; Drug: Ticagrelor; 120mg/day; Other Name: 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 Name: Clopidogrel or its generic; Drug: Ticagrelor; 120mg/day; Other Name: Brillinta; Drug: Aspirin; 100mg/day; Other Name: Any commercially available aspirin

Outcome Measures

Primary Outcome Measures :

1. A composite of death, myocardial infarction, and cerebrovascular events [ Time Frame: 36 months after the index procedure ]
   defined as MACCE

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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).

Contacts and Locations

Contacts

Contact: Joo-Yong Hahn, MD, PhD; 82-2-3410-6653; ichjy1@gmail.com

Contact: Joo Myung Lee, MD, MPH; 82-2-3410-1246; drone80@hanmail.net

Locations

Korea, Republic of

Samsung Medical Center; Recruiting

Seoul, Korea, Republic of, 06351

Contact: Joo-Yong Hahn, MD, PhD 82-2-3410-6653 ichjy1@gmail.com

Contact: Joo Myung Lee, MD, MPH 82-2-3410-1246 drone80@hanmail.net

Sponsors and Collaborators

Samsung Medical Center

Investigators

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

More Information

• Responsible Party: Joo-Yong Hahn, Professor, Samsung Medical Center
• ClinicalTrials.gov Identifier: NCT03119012 History of Changes
• Other Study ID Numbers: CHOICEII16453143
• First Posted: April 18, 2017
• Last Update Posted: April 9, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Joo-Yong Hahn, Samsung Medical Center:

Bioresorbable scaffold; Dual antiplatelet therapy; P2Y12 receptor inhibitor; Coronary artery disease

Additional relevant MeSH terms:

Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Atherosclerosis; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Aspirin; Clopidogrel; Ticagrelor; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists