ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-2 Study for the Patients With ACS (STOPDAPT-2 ACS)

Study to Evaluate the Safety of Reducing Dual Antiplatelet Therapy (DAPT) Duration to 1 Month for Patients With Acute Coronary Syndrome (ACS) After Implantation of Everolimus-eluting Cobalt-chromium Stent

The purpose of this study is to evaluate the safety of reducing dual antiplatelet therapy (DAPT) duration to 1 month after implantation of the everolimus-eluting cobalt-chromium stent (CoCr-EES) under the setting of acute coronary syndrome (ACS).

Study Overview

• Status: Active, not recruiting
• Conditions: Coronary Artery Disease; Acute Coronary Syndrome; Percutaneous Coronary Intervention; Acute Myocardial Infarction; Platelet Aggregation Inhibitors
• Intervention / Treatment: Drug: 1-months DAPT; Drug: 12-month DAPT

Detailed Description

The drug-eluting stents (DESs) are currently used in the majority of percutaneous coronary intervention (PCI) procedures. On the other hand, the problems of the first-generation DES (late adverse events, such as very late stent thrombosis) have been pointed out. Dual antiplatelet therapy (DAPT) has become a standard regimen after DES implantation and for fear of very late stent thrombosis, DAPT is frequently performed for 1 year or longer in clinical practice. Especially guidelines recommend 1-year DAPT for patients with acute coronary syndrome (ACS), though its rational is based on the study more than 15 years old. However, serious hemorrhagic complications associated with prolonged DAPT duration can bring disadvantages to patients, and it is extremely important to clarify an optimal DAPT duration after DES procedure. Currently, 1-month DAPT regimen after bare metal stent (BMS) implantation is commonly used in clinical practice, producing no major problems. Based on a meta-analysis of recent clinical studies, it has also been reported that the use of Cobalt-Chromium Everolimus-Eluting Stent (CoCr-EES) reduces the risk of early stent thrombosis by half compared to the use of BMS. There is no necessity to extend antiplatelet therapy after CoCr-EES implantation longer than after BMS implantation, and it is considered possible to use the same 1-month DAPT duration as after BMS implantation. The investigators already planned and started a multicenter, randomized, open-label, controlled study, in which the subjects who have undergone CoCr-EES procedure will be divided into the 1-month DAPT and clopidogrel monotherapy group and the 12-month DAPT and aspirin monotherapy group (STOPDAPT-2; NCT02619760), where primary endpoint is the incidence of composite events including cardiovascular death, myocardial infarction, stent thrombosis, stroke, and bleeding defined by TIMI major or minor bleeding. In STOPDAPT-2, the non-inferiority about primary endpoint of 1-month DAPT group will be evaluated at 12 months after index procedure and secondarily, the superiority about primary endpoint of 1-month DAPT group will be evaluated at 5 years after index procedure. The proportion of patients with ACS is about 30-40% in STOPDAPT-2 and the power is insufficient to evaluate the safety and efficacy of 1-month DAPT regimen specifically for patients with ACS. Therefore the investigators planned the current study to enroll patients of ACS with the same protocol as STOPDAPT-2.

• Study Type: Interventional
• Enrollment (Actual): 3008
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Kyoto, Japan, 606-8507
    • Kyoto University Graduate School of Medicine

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients received percutaneous coronary intervention with cobalt-chromium everolimus-eluting stent under the setting of acute coronary syndrome
• Patients who are capable of oral dual antiplatelet therapy consisting of aspirin and P2Y12 receptor antagonist

Exclusion Criteria:

• Patients requiring oral anticoagulants
• Patients with medical history of intracranial hemorrhage
• Patients who have experienced serious complications (myocardial infarction, stroke, and major bleeding) during hospital stay after percutaneous coronary intervention
• Patients with drug eluting stents other than Cobalt chromium everolimus eluting stents implanted at the time of enrollment
• Patients confirmed to have no tolerability to clopidogrel before enrollment
• Patients requiring continuous administration of antiplatelet drugs other than aspirin and P2Y12 receptor antagonists at the time of enrollment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1-month DAPT; 1-month dual antiplatelet therapy (DAPT) composed of aspirin and P2Y12 receptor antagonists and clopidogrel monotherapy for 59 months	Drug: 1-months DAPT; 1-month DAPT followed by 59-month monotherapy
Active Comparator: 12-month DAPT; 1-month dual antiplatelet therapy (DAPT) composed of aspirin and P2Y12 receptor antagonists; 11-month DAPT composed of aspirin and clopidogrel and aspirin monotherapy for 48 months	Drug: 12-month DAPT; 12-month DAPT followed by 48-month monotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke/bleeding defined as major or minor under the definition of Thrombolysis in Myocardial Infarction (TIMI) Study group	12 months
Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke/bleeding defined as major or minor under the definition of Thrombolysis in Myocardial Infarction (TIMI) Study group	60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular death		12 months
Stroke		12 months
Clinically-driven target lesion revascularization		60 months
Target vessel revascularization		12 months
Myocardial infarction		12 months
Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke		12 months
Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke		60 months
Bleeding defined as major or minor under the definition of Thrombolysis in Myocardial Infarction (TIMI) Study group		12 months
Bleeding defined as major or minor under the definition of Thrombolysis in Myocardial Infarction (TIMI) Study group		60 months
Upper gastrointestinal endoscopic examination or treatment		60 months
Composite event of all-cause death/myocardial infarction		12 months
Composite event of all-cause death/myocardial infarction		60 months
All-cause death		12 months
All-cause death		60 months
Composite event of cardiovascular death/myocardial infarction		12 months
Composite event of cardiovascular death/myocardial infarction		60 months
Cardiovascular death		60 months
Myocardial infarction		60 months
Stroke		60 months
Definite stent thrombosis	Academic Research Consortium definition	12 months
Definite stent thrombosis	Academic Research Consortium definition	60 months
Target lesion failure		12 months
Target lesion failure		60 months
Target vessel failure		12 months
Target vessel failure		60 months
Major adverse cardiac event	Composite of cardiac death, myocardial infarction, and clinically-driven TLR	12 months
Major adverse cardiac event	Composite of cardiac death, myocardial infarction, and clinically-driven TLR	60 months
Target lesion revascularization		12 months
Target lesion revascularization		60 months
Clinically-driven target lesion revascularization		12 months
Non target lesion revascularization		12 months
Non target lesion revascularization		60 months
Coronary artery bypass graft		12 months
Coronary artery bypass graft		60 months
Target vessel revascularization		60 months
Any coronary revascularization		12 months
Any coronary revascularization		60 months
Bleeding complications		12 months
Bleeding complications		60 months
Gastrointestinal bleeding		12 months
Gastrointestinal bleeding		60 months
Gastrointestinal complaints requiring upper gastrointestinal endoscopy		12 months
Gastrointestinal complaints requiring upper gastrointestinal endoscopy		60 months
Newly diagnosed cancer	The endpoint is a newly diagnosed malignancy during the follow-up period that has not been previously diagnosed before enrollment. This does not include recurrent tumor after remission, includes early-stage cancer eligible for endoscopic treatment, and includes the tumors which are not diagnosed by tissue biopsy but are judged to be clinically malignant on imaging.	60 months

Collaborators and Investigators

• Sponsor: Kyoto University, Graduate School of Medicine
• Investigators: Principal Investigator: Takeshi Kimura, MD, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine

Publications and helpful links

General Publications

• Obayashi Y, Watanabe H, Morimoto T, Yamamoto K, Natsuaki M, Domei T, Yamaji K, Suwa S, Isawa T, Watanabe H, Yoshida R, Sakamoto H, Akao M, Hata Y, Morishima I, Tokuyama H, Yagi M, Suzuki H, Wakabayashi K, Suematsu N, Inada T, Tamura T, Okayama H, Abe M, Kawai K, Nakao K, Ando K, Tanabe K, Ikari Y, Morino Y, Kadota K, Furukawa Y, Nakagawa Y, Kimura T; STOPDAPT-2 and STOPDAPT-2 ACS Investigators. Clopidogrel Monotherapy After 1-Month Dual Antiplatelet Therapy in Percutaneous Coronary Intervention: From the STOPDAPT-2 Total Cohort. Circ Cardiovasc Interv. 2022 Aug;15(8):e012004. doi: 10.1161/CIRCINTERVENTIONS.122.012004. Epub 2022 Aug 1.
• Watanabe H, Morimoto T, Natsuaki M, Yamamoto K, Obayashi Y, Ogita M, Suwa S, Isawa T, Domei T, Yamaji K, Tatsushima S, Watanabe H, Ohya M, Tokuyama H, Tada T, Sakamoto H, Mori H, Suzuki H, Nishikura T, Wakabayashi K, Hibi K, Abe M, Kawai K, Nakao K, Ando K, Tanabe K, Ikari Y, Morino Y, Kadota K, Furukawa Y, Nakagawa Y, Kimura T; STOPDAPT-2 ACS Investigators. Comparison of Clopidogrel Monotherapy After 1 to 2 Months of Dual Antiplatelet Therapy With 12 Months of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome: The STOPDAPT-2 ACS Randomized Clinical Trial. JAMA Cardiol. 2022 Apr 1;7(4):407-417. doi: 10.1001/jamacardio.2021.5244.

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2018
• Primary Completion (Actual): December 31, 2021
• Study Completion (Anticipated): March 31, 2026

Study Registration Dates

• First Submitted: March 6, 2018
• First Submitted That Met QC Criteria: March 6, 2018
• First Posted (Actual): March 12, 2018

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: April 1, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Acute Myocardial Infarction; Coronary Artery Disease; Percutaneous Coronary Intervention; Acute Coronary Syndrome; Platelet Aggregation Inhibitors
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Disease; Myocardial Infarction; Infarction; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Syndrome; Acute Coronary Syndrome
• Other Study ID Numbers: C1348

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