Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis- EXtended Antiplatelet Monotherapy (HOST-EXAM)

Sponsor

Seoul National University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02044250

Collaborator

Chong Kun Dang Pharmaceutical (Industry), Samjin Pharmaceutical Co., Ltd. (Industry), Daewoong Pharmaceutical Co. LTD. (Industry), Hanmi Pharmaceutical co., ltd. (Other)

5,530

Enrollment

Location

Arms

84.9

Actual Duration (Months)

65.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Objectives :

To compare the efficacy and safety of clopidogrel monotherapy with aspirin monotherapy in patients who received dual or triple antiplatelet therapy for 1 year (± 6 months) after drug-eluting stent implantation for coronary artery disease

Patient Enrollment :

5530 patients enrolled at 55 centers in Korea

Patient Follow-up :

Clinical follow-up will occur at 1, 12 and 24 months.

Primary Endpoint :

Composite endpoint of MACE and major bleeding

Secondary Endpoint :

Device-oriented composite outcome including TLR (target lesion revascularization), TVR (target vessel revascularization), stent thrombosis, and minor GI (gastrointestinal) complications

Condition or Disease	Intervention/Treatment	Phase
Coronary Heart Disease	Drug: Clopidogrel Drug: Aspirin	Phase 4

Detailed Description

The primary purpose of this study is to compare the efficacy and safety of antiplatelet monotherapy with aspirin or clopidogrel for 2 years in patients who have not experienced MACE (major adverse cardiac events) including all-cause death, acute coronary syndrome including non-fatal MI (myocardial infarction), or urgent revascularization under combined antiplatelet therapy for 12 ± 6 months after PCI (percutaneous coronary intervention) with DES (drug-eluting stents). The trial tests the hypothesis that clopidogrel is superior to aspirin in preventing clinical events and device-oriented outcomes. Clinical events are defined as a composite of all-cause death, non-fatal MI, stroke, readmission due to acute coronary syndrome (ACS), or Bleeding Academic Research Consortium (BARC) class ≥ 3.29 Device-oriented outcomes include target lesion/vessel revascularization (TLR/TVR) and Academic Research Consortium (ARC)-defined stent thrombosis.

The primary endpoint of this study is the rate of clinical events defined as a composite of MACE and major bleeding complications. MACE includes all-cause death, non-fatal MI, stroke, and readmission due to ACS (acute coronary syndrome). Major bleeding is defined as bleeding (BARC class ≥ 3) at 24 months. Non-fatal MI is defined as any confirmed evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia without resulting in death, which is supported by electrocardiography, cardiac enzymes, or cardiac imaging according to the third Universal Definition of MI.37, 38 A readmission due to ACS is defined as any re-hospitalization definitely originating from an ACS event, which satisfies the definition of the American College of Cardiology Foundation and the American Heart Association.37, 39 A stroke is defined as any abrupt-onset, non-convulsive, focal, or global neurological deficit lasting more than 24 hours, which is caused by ischemia or hemorrhage in the brain.39 Secondary endpoints are the rate of device-oriented outcomes including TLR/TVR and stent thrombosis at 24 months, and minor gastrointestinal (GI) complications with the related cost-effectiveness. TLR is defined as any repeat revascularization procedure at the original lesion of the index procedure any time during the follow-up period.40 TVR is defined as any repeat revascularization procedure involving at least one of the target vessels that were treated in the index procedure.40 Stent thrombosis is defined according to the ARC.41, 42 Minor GI complications are assessed on the basis of newly developed GI symptoms, newly added GI medications, or symptom-driven GI endoscopy. At each visit, clinicians will question the patient regarding GI symptoms from intermittent epigastric soreness or bloating due to melena/hematochezia. Any additional GI medications, including H2-blockers and proton pump inhibitors, will be documented for each patient. If a patient undergoes endoscopy, the type of endoscopy, test results, and further interventions will be recorded. Additional medical costs related to these minor GI complications (South Korean won/year) will be calculated to assess the cost effectiveness of each drug based on average Korean expenses. All endpoints will be assessed primarily by the investigator and adjudicated secondarily by the independent clinical event committee.

Study Design

Study Type:

Interventional

Actual Enrollment :

5530 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Comparison of Clopidogrel vs. Aspirin Monotherapy Beyond Two Year After Drug-eluting Stent Implantation

Actual Study Start Date :

Feb 1, 2014

Actual Primary Completion Date :

Aug 1, 2020

Actual Study Completion Date :

Mar 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Clopidogrel Antiplatelet monotherapy : Clopidogrel 75mg P.O. daily	Drug: Clopidogrel Clopidogrel 75mg 1tab P.O. daily Other Names: Copregrel, Plateless, Cloart, Pidogul
Placebo Comparator: Aspirin Antiplatelet monotherapy : Aspirin 100~200mg P.O. daily	Drug: Aspirin Aspirin 100~200mg 1~2tab P.O. daily

Arm

Intervention/Treatment

Active Comparator: Clopidogrel

Antiplatelet monotherapy : Clopidogrel 75mg P.O. daily

Drug: Clopidogrel

Clopidogrel 75mg 1tab P.O. daily

Other Names:

Copregrel, Plateless, Cloart, Pidogul

Placebo Comparator: Aspirin

Antiplatelet monotherapy : Aspirin 100~200mg P.O. daily

Drug: Aspirin

Aspirin 100~200mg 1~2tab P.O. daily

Outcome Measures

Primary Outcome Measures

Composite of major adverse cardiovascular events (MACE) and major bleeding complications [2 years]
MACE, composite of all-cause death, non-fatal MI, stroke, and readmission due to ACS; major bleeding, bleeding of BARC class ≥3

Secondary Outcome Measures

Target vessel revascularization (TVR), target lesion revascularization (TLR) [2 years]
TVR, any repeat revascularization procedure involving at least one of the target vessels that were treated in the index procedure; TLR, any repeat revascularization procedure at the original lesion of the index procedure
Stent thrombosis (acute, sub-acute, late, very late) [2 years]
defined according to the ARC
Minor gastrointestinal (GI) complications [2 years]
newly developed GI symptoms, newly added GI medications, or symptom-driven GI endoscopy

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and female aged ≥20 years
Maintenance of dual or triple antiplatelet therapy at least 12 ± 6 months after PCI with DES
No history of further clinical event after PCI with DES
Plan to change to antiplatelet monotherapy
Agreement to give written informed consent

Exclusion Criteria:

History of hypersensitivity to aspirin or clopidogrel
History of contraindication to aspirin or clopidogrel
Active pathologic bleeding, such as peptic ulcer, tumor bleeding or intracranial hemorrhage
History of major bleeding, BARC class ≥3, resulting in stop of antiplatelet agents within 3 months
Bleeding diathesis
Known coagulopathy or refusal of blood transfusion
Presence of non-cardiac comorbidity with life expectancy <2 years from randomization
Plan to surgery or intervention which needs to stop antiplatelet agents ≥3 months
Females with childbearing potential or breast-feeding
Conditions that may result in protocol non-compliance by the committees
Co-administration of contraindicated medications as follows: other P2Y 12 inhibitors (prasugrel or ticagrelor); anticoagulants (warfarin, new oral anticoagulants, or chronic therapy of heparin); cytochrome P450 2C19 inhibitors (fluoxetine, moclobemid or voriconazole); probenecid; high dose of methotrexate (≥15 mg/week); lithium
Refusal to give written informed consent