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

• ClinicalTrials.gov Identifier: NCT03462498
• Recruitment Status: Active, not recruiting
• First Posted: March 12, 2018
• Last Update Posted: April 4, 2023
• Sponsor: Kyoto University, Graduate School of Medicine
• Information provided by (Responsible Party): Takeshi Morimoto, Kyoto University, Graduate School of Medicine

Tracking Information

• First Submitted Date: March 6, 2018
• First Posted Date: March 12, 2018
• Last Update Posted Date: April 4, 2023
• Actual Study Start Date: April 2, 2018
• Actual Primary Completion Date: December 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 6, 2018)

• 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 [ Time Frame: 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 [ Time Frame: 60 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 18, 2021)

• Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke [ Time Frame: 12 months ]
• Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke [ Time Frame: 60 months ]
• Bleeding defined as major or minor under the definition of Thrombolysis in Myocardial Infarction (TIMI) Study group [ Time Frame: 12 months ]
• Bleeding defined as major or minor under the definition of Thrombolysis in Myocardial Infarction (TIMI) Study group [ Time Frame: 60 months ]
• Upper gastrointestinal endoscopic examination or treatment [ Time Frame: 60 months ]
• Composite event of all-cause death/myocardial infarction [ Time Frame: 12 months ]
• Composite event of all-cause death/myocardial infarction [ Time Frame: 60 months ]
• All-cause death [ Time Frame: 12 months ]
• All-cause death [ Time Frame: 60 months ]
• Composite event of cardiovascular death/myocardial infarction [ Time Frame: 12 months ]
• Composite event of cardiovascular death/myocardial infarction [ Time Frame: 60 months ]
• Cardiovascular death [ Time Frame: 12 months ]
• Cardiovascular death [ Time Frame: 60 months ]
• Myocardial infarction [ Time Frame: 12 months ]
• Myocardial infarction [ Time Frame: 60 months ]
• Stroke [ Time Frame: 12 months ]
• Stroke [ Time Frame: 60 months ]
• Definite stent thrombosis [ Time Frame: 12 months ]
  Academic Research Consortium definition
• Definite stent thrombosis [ Time Frame: 60 months ]
  Academic Research Consortium definition
• Target lesion failure [ Time Frame: 12 months ]
• Target lesion failure [ Time Frame: 60 months ]
• Target vessel failure [ Time Frame: 12 months ]
• Target vessel failure [ Time Frame: 60 months ]
• Major adverse cardiac event [ Time Frame: 12 months ]
  Composite of cardiac death, myocardial infarction, and clinically-driven TLR
• Major adverse cardiac event [ Time Frame: 60 months ]
  Composite of cardiac death, myocardial infarction, and clinically-driven TLR
• Target lesion revascularization [ Time Frame: 12 months ]
• Target lesion revascularization [ Time Frame: 60 months ]
• Clinically-driven target lesion revascularization [ Time Frame: 12 months ]
• Clinically-driven target lesion revascularization [ Time Frame: 60 months ]
• Non target lesion revascularization [ Time Frame: 12 months ]
• Non target lesion revascularization [ Time Frame: 60 months ]
• Coronary artery bypass graft [ Time Frame: 12 months ]
• Coronary artery bypass graft [ Time Frame: 60 months ]
• Target vessel revascularization [ Time Frame: 12 months ]
• Target vessel revascularization [ Time Frame: 60 months ]
• Any coronary revascularization [ Time Frame: 12 months ]
• Any coronary revascularization [ Time Frame: 60 months ]
• Bleeding complications [ Time Frame: 12 months ]
• Bleeding complications [ Time Frame: 60 months ]
• Gastrointestinal bleeding [ Time Frame: 12 months ]
• Gastrointestinal bleeding [ Time Frame: 60 months ]
• Gastrointestinal complaints requiring upper gastrointestinal endoscopy [ Time Frame: 12 months ]
• Gastrointestinal complaints requiring upper gastrointestinal endoscopy [ Time Frame: 60 months ]
• Newly diagnosed cancer [ Time Frame: 60 months ]
  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.

Original Secondary Outcome Measures (submitted: March 6, 2018)

• Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke [ Time Frame: 12 months ]
• Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke [ Time Frame: 60 months ]
• Bleeding defined as major or minor under the definition of Thrombolysis in Myocardial Infarction (TIMI) Study group [ Time Frame: 12 months ]
• Bleeding defined as major or minor under the definition of Thrombolysis in Myocardial Infarction (TIMI) Study group [ Time Frame: 60 months ]
• Upper gastrointestinal endoscopic examination or treatment [ Time Frame: 60 months ]
• Composite event of all-cause death/myocardial infarction [ Time Frame: 12 months ]
• Composite event of all-cause death/myocardial infarction [ Time Frame: 60 months ]
• All-cause death [ Time Frame: 12 months ]
• All-cause death [ Time Frame: 60 months ]
• Composite event of cardiovascular death/myocardial infarction [ Time Frame: 12 months ]
• Composite event of cardiovascular death/myocardial infarction [ Time Frame: 60 months ]
• Cardiovascular death [ Time Frame: 12 months ]
• Cardiovascular death [ Time Frame: 60 months ]
• Myocardial infarction [ Time Frame: 12 months ]
• Myocardial infarction [ Time Frame: 60 months ]
• Stroke [ Time Frame: 12 months ]
• Stroke [ Time Frame: 60 months ]
• Definite stent thrombosis [ Time Frame: 12 months ]
  Academic Research Consortium definition
• Definite stent thrombosis [ Time Frame: 60 months ]
  Academic Research Consortium definition
• Target lesion failure [ Time Frame: 12 months ]
• Target lesion failure [ Time Frame: 60 months ]
• Target vessel failure [ Time Frame: 12 months ]
• Target vessel failure [ Time Frame: 60 months ]
• Major adverse cardiac event [ Time Frame: 12 months ]
  Composite of cardiac death, myocardial infarction, and clinically-driven TLR
• Major adverse cardiac event [ Time Frame: 60 months ]
  Composite of cardiac death, myocardial infarction, and clinically-driven TLR
• Target lesion revascularization [ Time Frame: 12 months ]
• Target lesion revascularization [ Time Frame: 60 months ]
• Clinically-driven target lesion revascularization [ Time Frame: 12 months ]
• Clinically-driven target lesion revascularization [ Time Frame: 60 months ]
• Non target lesion revascularization [ Time Frame: 12 months ]
• Non target lesion revascularization [ Time Frame: 60 months ]
• Coronary artery bypass graft [ Time Frame: 12 months ]
• Coronary artery bypass graft [ Time Frame: 60 months ]
• Target vessel revascularization [ Time Frame: 12 months ]
• Target vessel revascularization [ Time Frame: 60 months ]
• Any coronary revascularization [ Time Frame: 12 months ]
• Any coronary revascularization [ Time Frame: 60 months ]
• Bleeding complications [ Time Frame: 12 months ]
• Bleeding complications [ Time Frame: 60 months ]
• Gastrointestinal bleeding [ Time Frame: 12 months ]
• Gastrointestinal bleeding [ Time Frame: 60 months ]
• Gastrointestinal complaints requiring upper gastrointestinal endoscopy [ Time Frame: 12 months ]
• Gastrointestinal complaints requiring upper gastrointestinal endoscopy [ Time Frame: 60 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-2 Study for the Patients With ACS
• Official Title: 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
• Brief Summary: 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).
• 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
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

• Acute Coronary Syndrome
• Acute Myocardial Infarction
• Coronary Artery Disease
• Percutaneous Coronary Intervention
• Platelet Aggregation Inhibitors

Intervention

• Drug: 1-months DAPT
  1-month DAPT followed by 59-month monotherapy
• Drug: 12-month DAPT
  12-month DAPT followed by 48-month monotherapy

Study Arms

• Active Comparator: 1-month DAPT
  1-month dual antiplatelet therapy (DAPT) composed of aspirin and P2Y12 receptor antagonists and clopidogrel monotherapy for 59 months
  Intervention: Drug: 1-months DAPT
• 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
  Intervention: Drug: 12-month DAPT

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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 11, 2020): 3008
• Original Estimated Enrollment (submitted: March 6, 2018): 3000
• Estimated Study Completion Date: March 31, 2026
• Actual Primary Completion Date: December 31, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT03462498
• Other Study ID Numbers: C1348
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Takeshi Morimoto, Kyoto University, Graduate School of Medicine
• Original Responsible Party: Same as current
• Current Study Sponsor: Kyoto University, Graduate School of Medicine
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Kyoto University, Graduate School of Medicine
• Verification Date: April 2023