ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-2 Study (STOPDAPT-2)

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).

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: 1-month 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. However, serious hemorrhagic complications associated with a 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 therefore planned 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. 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. At first, 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.

• Study Type: Interventional
• Enrollment (Actual): 3045
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Kyoto, Japan, 606-8507
    • Division of Cardiology, Kyoto University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients received percutaneous coronary intervention with cobalt-chromium everolimus-eluting stent
• Patients who are capable of oral dual antiplatelet therapy consisting of asprin 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 (Xience) implanted at the time of enrollment
• Patients comfirmed to have no tolerability to clopidgorel before enrollment
• Patients requiring continuous administration of antiplaelet drugs other than aspirin and P2Y12 receptor antagonists at the time of enrollment
• Patients with coronary bioabsorbable vascular scaffolds (BVS) implanted prior to or at the time of enrollment

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: 1-month DAPT; 1-month dual antiplatelet therapy (DAPT) composed of aspirin and P2Y12 receptor antagonists , followed by 59-month clopidogrel monotherapy	Drug: 1-month DAPT; 1-month dual antiplatelet therapy (DAPT) composed of aspirin and P2Y12 receptor antagonists
Active Comparator: 12-month DAPT; 1-month dual antiplatelet therapy (DAPT) composed of aspirin and P2Y12 receptor antagonists with 11-month DAPT composed of aspirin and clopidogrel, followed by 48-month aspirin monotherapy	Drug: 12-month DAPT; 12-month dual antiplatelet therapy (DAPT) composed of aspirin and P2Y12 receptor antagonists

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke/bleeding	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-month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial infarction		12-month
Target vessel revascularization		12-month
Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke		12-month
Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke		60-month
Bleeding defined as major or minor under the definition of Thrombolysis in Myocardial Infarction (TIMI) Study group		12-month
Bleeding defined as major or minor under the definition of Thrombolysis in Myocardial Infarction (TIMI) Study group		60-month
Upper gastrointestinal endoscopic examination or treatment		60-month
Composite event of all-cause death/myocardial infarction		12-month
Composite event of all-cause death/myocardial infarction		60-month
All-cause death		12-month
All-cause death		60-month
Composite event of cardiovascular death/myocardial infarction		12-month
Composite event of cardiovascular death/myocardial infarction		60-month
Cardiovascular death		12-month
Cardiovascular death		60-month
Myocardial infarction		60-month
Stroke	a neurological deficit with acute onset that persists for at least 24 hours caused by a disturbance of the cerebral circulation due to ischemia or hemorrhage	12-month
Stroke	a neurological deficit with acute onset that persists for at least 24 hours caused by a disturbance of the cerebral circulation due to ischemia or hemorrhage	60-month
MACE (Major Adverse Cardiac Events)	Composite event of cardiac death, myocardial infarction and clinically-indicated target vesion revascularization	12-month
MACE (Major Adverse Cardiac Events)	Composite event of cardiac death, myocardial infarction and clinically-indicated target vesion revascularization	60-month
Definite stent thrombosis		12-month
Definite stent thrombosis		60-month
Target lesion failure	Composite event of cardiac death, myocardial infarction (MI) of target vessels, and Clinically-indicated TLR	12-month
Target lesion failure	Composite event of cardiac death, myocardial infarction (MI) of target vessels, and Clinically-indicated TLR	60-month
Target vessel failure		12-month
Target vessel failure		60-month
Target lesion revasucularization	PCI performed in the target lesion (within 5 mm of the stent edges), or CABG performed for restenosis of the target lesion or for treatment of other complications	12-month
Target lesion revasucularization	PCI performed in the target lesion (within 5 mm of the stent edges), or CABG performed for restenosis of the target lesion or for treatment of other complications	60-month
Clinically-driven target lesion revascularization	the revascularization that meets the following criteria; (1) recurrence of angina pectoris, presumably related to the target vessel, (2) objective signs of ischemia at rest or during exercise test (or equivalent), presumably related to the target vessel, (3) Signs of functional ischemia revealed by any invasive diagnostic test (e.g., Doppler flow velocity reserve [FVR], fractional flow reserve [FFR]), and (4) revascularization for ≥ 70% diameter stenosis even in the absence of the above-mentioned ischemic signs or symptoms. Presence/absence of clinical findings is judged by the operator of the procedure before the revascularization.	12-month
Clinically-driven target lesion revascularization	the revascularization that meets the following criteria; (1) recurrence of angina pectoris, presumably related to the target vessel, (2) objective signs of ischemia at rest or during exercise test (or equivalent), presumably related to the target vessel, (3) Signs of functional ischemia revealed by any invasive diagnostic test (e.g., Doppler flow velocity reserve [FVR], fractional flow reserve [FFR]), and (4) revascularization for ≥ 70% diameter stenosis even in the absence of the above-mentioned ischemic signs or symptoms. Presence/absence of clinical findings is judged by the operator of the procedure before the revascularization.	60-month
Non target lesion revascularization		12-month
Non target lesion revascularization		60-month
Coronary artery bypass graft		12-month
Coronary artery bypass graft		60-month
Target vessel revascularization		60-month
Any coronary reascluarization		12-month
Any coronary reascluarization		60-month
Bleeding complications	Evaluated with TIMI (major/minor/minimal), GUSTO (severe/moderate) and BARC (Type 1, 2, 3a, 3b, 3c, 4, 5a, 5b)	12-month
Bleeding complications	Evaluated with TIMI (major/minor/minimal), GUSTO (severe/moderate) and BARC (Type 1, 2, 3a, 3b, 3c, 4, 5a, 5b)	60-month
Gastrointestinal bleeding	Bleeding events requiring upper gastrointestinal endoscopic study or treatment.	12-month
Gastrointestinal bleeding	Bleeding events requiring upper gastrointestinal endoscopic study or treatment.	60-month
Gastrointestinal complaints	Symptoms requiring upper gastrointestinal endoscopic study or treatment	12-month
Gastrointestinal complaints	Symptoms requiring upper gastrointestinal endoscopic study or treatment	60-month
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-month

Collaborators and Investigators

• Sponsor: Kyoto University, Graduate School of Medicine
• Investigators: Study Chair: Takeshi Kimura, MD, PhD, Professor of Medicine, 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.
• Yamamoto K, Watanabe H, Morimoto T, Domei T, Ohya M, Ogita M, Takagi K, Suzuki H, Nikaido A, Ishii M, Fujii S, Natsuaki M, Yasuda S, Kaneko T, Tamura T, Tamura T, Abe M, Kawai K, Nakao K, Ando K, Tanabe K, Ikari Y, Igarashi Hanaoka K, Morino Y, Kozuma K, Kadota K, Furukawa Y, Nakagawa Y, Kimura T; STOPDAPT-2 Investigators. Very Short Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Patients Who Underwent Complex Percutaneous Coronary Intervention: Insight From the STOPDAPT-2 Trial. Circ Cardiovasc Interv. 2021 May;14(5):e010384. doi: 10.1161/CIRCINTERVENTIONS.120.010384. Epub 2021 May 18.
• Watanabe H, Morimoto T, Ogita M, Suwa S, Natsuaki M, Suematsu N, Koeda Y, Morino Y, Nikaido A, Hata Y, Doi M, Hibi K, Kimura K, Yoda S, Kaneko T, Nishida K, Kawai K, Yamaguchi K, Wakatsuki T, Tonoike N, Yamamoto M, Shimizu S, Shimohama T, Ako J, Kimura T; STOPDAPT-2 Investigators. Influence of CYP2C19 genotypes for the effect of 1-month dual antiplatelet therapy followed by clopidogrel monotherapy relative to 12-month dual antiplatelet therapy on clinical outcomes after percutaneous coronary intervention: a genetic substudy from the STOPDAPT-2. Cardiovasc Interv Ther. 2021 Oct;36(4):403-415. doi: 10.1007/s12928-020-00719-6. Epub 2020 Nov 12. Erratum In: Cardiovasc Interv Ther. 2021 Feb 12;:
• Watanabe H, Domei T, Morimoto T, Natsuaki M, Shiomi H, Toyota T, Ohya M, Suwa S, Takagi K, Nanasato M, Hata Y, Yagi M, Suematsu N, Yokomatsu T, Takamisawa I, Doi M, Noda T, Okayama H, Seino Y, Tada T, Sakamoto H, Hibi K, Abe M, Kawai K, Nakao K, Ando K, Tanabe K, Ikari Y, Hanaoka KI, Morino Y, Kozuma K, Kadota K, Furukawa Y, Nakagawa Y, Kimura T; STOPDAPT-2 investigators. Details on the effect of very short dual antiplatelet therapy after drug-eluting stent implantation in patients with high bleeding risk: insight from the STOPDAPT-2 trial. Cardiovasc Interv Ther. 2021 Jan;36(1):91-103. doi: 10.1007/s12928-020-00651-9. Epub 2020 Feb 21.
• Watanabe H, Domei T, Morimoto T, Natsuaki M, Shiomi H, Toyota T, Ohya M, Suwa S, Takagi K, Nanasato M, Hata Y, Yagi M, Suematsu N, Yokomatsu T, Takamisawa I, Doi M, Noda T, Okayama H, Seino Y, Tada T, Sakamoto H, Hibi K, Abe M, Kawai K, Nakao K, Ando K, Tanabe K, Ikari Y, Hanaoka KI, Morino Y, Kozuma K, Kadota K, Furukawa Y, Nakagawa Y, Kimura T; STOPDAPT-2 Investigators. Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCI: The STOPDAPT-2 Randomized Clinical Trial. JAMA. 2019 Jun 25;321(24):2414-2427. doi: 10.1001/jama.2019.8145.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): December 8, 2018
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: November 29, 2015
• First Submitted That Met QC Criteria: November 29, 2015
• First Posted (Estimated): December 2, 2015

Study Record Updates

• Last Update Posted (Actual): June 14, 2024
• Last Update Submitted That Met QC Criteria: June 12, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: C1114; UMIN000019948 (Other Identifier: UMIN)