A Randomized Comparison of CLOpidogrel Monotherapy Versus Extended Dual-antiplatelet Therapy Beyond 12 Months After Implantation of Drug-eluting StEnts in High-risk Lesions or Patients; A-CLOSE Trial

• ClinicalTrials.gov Identifier: NCT03947229
• Recruitment Status: Recruiting
• First Posted: May 13, 2019
• Last Update Posted: August 22, 2019
• Sponsor: Yonsei University
• Information provided by (Responsible Party): Yonsei University

Study Description

Brief Summary:

The investigators hypothesized that clopidogrel mono-therapy will not be inferior to the extended DAPT in terms of the occurrence of both ischemic and bleeding events, for lesions or patients at high risk for either ischemic or bleeding complications 12 months after drug-eluting stent (DES) implantation.

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease; DES	Drug: Clopidogrel mono-therapy; Drug: Dual-antiplatelet therapy	Phase 4

Detailed Description:

Patients at high risk for either ischemic or bleeding complications, but who were stable without clinical events for 12 months after DES implantation will be included in this study. Eligible patients will be randomized to continue DAPT (aspirin plus clopidogrel) for further 24 months or to change to single antiplatelet therapy with clopidogrel (clopidogrel-alone). Randomization will be stratified according to 1) clinical presentation (acute coronary syndrome or stable coronary artery disease) and 2) age (≥75 or <75). Baseline clinical and angiographic characteristics, laboratory findings will be assessed at the time of randomization. All patients will provide informed consent on their own initiative. All of study subjects will be have an outpatient visit as scheduled in outpatient clinic. Occurrence of study endpoints will be documented at clinical visit or telephone interview every 6 months since randomization. Antiplatelet drugs will be open-label and prescribed by attending physician.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 3200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients will be assigned to continue DAPT (aspirin plus clopidogrel) or to change to single antiplatelet therapy with clopidogrel (clopidogrel-alone) for further 24 months.
• Masking: None (Open Label)
• Masking Description: Antiplatelet drugs will be open-label and prescribed by attending physician.
• Primary Purpose: Treatment
• Official Title: A Randomized Comparison of CLOpidogrel Monotherapy Versus Extended Dual-antiplatelet Therapy Beyond 12 Months After Implantation of Drug-eluting StEnts in High-risk Lesions or Patients; A-CLOSE Trial
• Actual Study Start Date: August 14, 2019
• Estimated Primary Completion Date: April 2022
• Estimated Study Completion Date: April 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Clopidogrel mono-therapy; After randomization, patients will receive clopidogrel monotherapy after DES implantation for 24 months.	Drug: Clopidogrel mono-therapy; Patients will receive clopidogrel (75 mg once daily) monotherapy without co-administration of aspirin for 24 months after randomization.
Active Comparator: Dual-antiplatelet therapy; Patients will receive dual antiplatelet consisting of aspirin and clopidogrel.	Drug: Dual-antiplatelet therapy; Patients will receive co-administration of aspirin (100 mg/day) and clopidogrel (75 mg/day) for 24 months after randomization.

Outcome Measures

Primary Outcome Measures :

1. Net Adverse Clinical Events (NACE) [ Time Frame: 24 months ]
   The composite of all-cause of death, myocardial infarction (MI), stent thrombosis, stroke, or bleeding (BARC type 2, 3, or 5)

Secondary Outcome Measures :

1. Each component of net adverse clinical events [ Time Frame: 24 months ]
2. All-cause or cardiovascular mortality [ Time Frame: 24 months ]
3. Major or minor bleeding [ Time Frame: 24 months ]
   Major or minor bleeding would be defined by BARC and TIMI criteria
4. Major adverse cardiac event [ Time Frame: 24 months ]
   Major Adverse Cardiac events includes all-cause of death, myocardial infarctions, stent thrombosis, or stroke.

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patients >19 years old
2. Patients who underwent DES implantation 12 months (+5 months) previously.
3. High risk characteristics (clinical or lesion) for ischemic events (must at least one)

High risk patients; clinical criteria

1. Acute coronary syndrome
2. Previous history of cerebrovascular accidents
3. History of peripheral artery intervention
4. Heart failure (left ventricular ejection fraction ≤40%)
5. Diabetes treated with medication
6. Chronic renal insufficiency including end-stage renal diseases

High risk lesions; angiographic or procedural criteria

1. Left main diseases
2. Bifurcation lesions
3. Chronic total occlusion
4. In-stent restenotic lesions
5. Graft lesions
6. Diffuse long lesions requiring total stent length ≥28 mm
7. Calcified lesions requiring atherectomy
8. Multivessel coronary artery disease with multiple stents
9. Small vessel disease requiring stent diameter of ≤2.5 mm

Exclusion Criteria:

1. Age> 80 years
2. Pregnant women or women with potential childbearing
3. Life expectancy < 1 year
4. Refusal or inability to understand of informed consent

Contacts and Locations

Locations

Korea, Republic of

Division of Cardiology, Severance Cardiovascular Hospital Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu 120-752 Seoul, South Korea; Recruiting

Seoul, Korea, Republic of

Contact: Byeong-Keuk Kim, PhD 82-2-2228-8460 kimbk@yuhs.ac

Sponsors and Collaborators

Yonsei University

More Information

• Responsible Party: Yonsei University
• ClinicalTrials.gov Identifier: NCT03947229 History of Changes
• Other Study ID Numbers: 4-2019-0234
• First Posted: May 13, 2019
• Last Update Posted: August 22, 2019
• Last Verified: August 2019

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

Keywords provided by Yonsei University:

Patients who underwent percutaneous coronary intervention with DES implantation carrying high risks for the recurrent major adverse events.; anti platelet therapy; bleeding

Additional relevant MeSH terms:

Myocardial Ischemia; Aspirin; Clopidogrel; Coronary Artery Disease; Coronary Disease; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; 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; Purinergic Agents; Neurotransmitter Agents