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

• Sponsor: Kyoto University, Graduate School of Medicine
• Information provided by (Responsible Party): Takeshi Morimoto, Kyoto University, Graduate School of Medicine

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease	Drug: 1-month DAPT; Drug: 12-month DAPT	Phase 4

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. We therefore planned a multicenter, randomized, open-label, controlled study, in which the subjects who have undergone CoCr-EES procedure will be diveded 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-inferiorty 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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3045 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-2 Study
• Actual Study Start Date: December 2015
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke/bleeding [ Time Frame: 12-month ]
   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

Secondary Outcome Measures :

1. Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke [ Time Frame: 12-month ]
2. Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke [ Time Frame: 60-month ]
3. Bleeding defined as major or minor under the definition of Thrombolysis in Myocardial Infarction (TIMI) Study group [ Time Frame: 12-month ]
4. Bleeding defined as major or minor under the definition of Thrombolysis in Myocardial Infarction (TIMI) Study group [ Time Frame: 60-month ]
5. Upper gastrointestinal endoscopic examination or treatment [ Time Frame: 60-month ]
6. Composite event of all-cause death/myocardial infarction [ Time Frame: 12-month ]
7. Composite event of all-cause death/myocardial infarction [ Time Frame: 60-month ]
8. All-cause death [ Time Frame: 12-month ]
9. All-cause death [ Time Frame: 60-month ]
10. Composite event of cardiovascular death/myocardial infarction [ Time Frame: 12-month ]
11. Composite event of cardiovascular death/myocardial infarction [ Time Frame: 60-month ]
12. Cardiovascular death [ Time Frame: 12-month ]
13. Cardiovascular death [ Time Frame: 60-month ]
14. Myocardial infarction [ Time Frame: 12-month ]
15. Myocardial infarction [ Time Frame: 60-month ]
16. Stroke [ Time Frame: 12-month ]
    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
17. Stroke [ Time Frame: 60-month ]
    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
18. MACE (Major Adverse Cardiac Events) [ Time Frame: 12-month ]
    Composite event of cardiac death, myocardial infarction and clinically-indicated target vesion revascularization
19. MACE (Major Adverse Cardiac Events) [ Time Frame: 60-month ]
    Composite event of cardiac death, myocardial infarction and clinically-indicated target vesion revascularization
20. Definite stent thrombosis [ Time Frame: 12-month ]
21. Definite stent thrombosis [ Time Frame: 60-month ]
22. Target lesion failure [ Time Frame: 12-month ]
    Composite event of cardiac death, myocardial infarction (MI) of target vessels, and Clinically-indicated TLR
23. Target lesion failure [ Time Frame: 60-month ]
    Composite event of cardiac death, myocardial infarction (MI) of target vessels, and Clinically-indicated TLR
24. Target vessel failure [ Time Frame: 12-month ]
25. Target vessel failure [ Time Frame: 60-month ]
26. Target lesion revasucularization [ Time Frame: 12-month ]
    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
27. Target lesion revasucularization [ Time Frame: 60-month ]
    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
28. Clinically-driven target lesion revascularization [ Time Frame: 12-month ]
    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.
29. Clinically-driven target lesion revascularization [ Time Frame: 60-month ]
    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.
30. Non target lesion revascularization [ Time Frame: 12-month ]
31. Non target lesion revascularization [ Time Frame: 60-month ]
32. Coronary artery bypass graft [ Time Frame: 12-month ]
33. Coronary artery bypass graft [ Time Frame: 60-month ]
34. Target vessel revascularization [ Time Frame: 12-month ]
35. Target vessel revascularization [ Time Frame: 60-month ]
36. Any coronary reascluarization [ Time Frame: 12-month ]
37. Any coronary reascluarization [ Time Frame: 60-month ]
38. Bleeding complications [ Time Frame: 12-month ]
    Evaluated with TIMI (major/minor/minimal), GUSTO (severe/moderate) and BARC (Type 1, 2, 3a, 3b, 3c, 4, 5a, 5b)
39. Bleeding complications [ Time Frame: 60-month ]
    Evaluated with TIMI (major/minor/minimal), GUSTO (severe/moderate) and BARC (Type 1, 2, 3a, 3b, 3c, 4, 5a, 5b)
40. Gastrointestinal bleeding [ Time Frame: 12-month ]
    Bleeding events requiring upper gastrointestinal endoscopic study or treatment.
41. Gastrointestinal bleeding [ Time Frame: 60-month ]
    Bleeding events requiring upper gastrointestinal endoscopic study or treatment.
42. Gastrointestinal complaints [ Time Frame: 12-month ]
    Symptoms requiring upper gastrointestinal endoscopic study or treatment
43. Gastrointestinal complaints [ Time Frame: 60-month ]
    Symptoms requiring upper gastrointestinal endoscopic study or treatment

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Japan

Division of Cardiology, Kyoto University Hospital

Kyoto, Japan, 606-8507

Sponsors and Collaborators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Takeshi Morimoto, Professor of Medicine, Kyoto University, Graduate School of Medicine
• ClinicalTrials.gov Identifier: NCT02619760 History of Changes
• Other Study ID Numbers: C1114; UMIN000019948 ( Other Identifier: UMIN )
• First Posted: December 2, 2015
• Last Update Posted: March 1, 2019
• Last Verified: February 2019

Keywords provided by Takeshi Morimoto, Kyoto University, Graduate School of Medicine:

Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors

Additional relevant MeSH terms:

Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Aspirin; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; 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; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents