Clinical trial NCT02044250: Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis- EXtended Antiplatelet Monotherapy (HOST-EXAM)
Official title: Comparison of Clopidogrel vs. Aspirin Monotherapy Beyond Two Year After Drug-eluting Stent Implantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Heart Disease
Keywords: Aspirin
Clopidogrel
Antiplatelet monotherapy
Drug-eluting stent
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Chong Kun Dang Pharmaceutical
name: Samjin Pharmaceutical Co., Ltd.
name: Daewoong Pharmaceutical Co. LTD.
name: Hanmi Pharmaceutical co., ltd.
First posted: 2014-01-23
Enrollment: 5530
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. History of hypersensitivity to aspirin or clopidogrel
2. History of contraindication to aspirin or clopidogrel
3. Active pathologic bleeding, such as peptic ulcer, tumor bleeding or intracranial hemorrhage
4. History of major bleeding, BARC class ≥3, resulting in stop of antiplatelet agents within 3 months
5. Bleeding diathesis
6. Known coagulopathy or refusal of blood transfusion
7. Presence of non-cardiac comorbidity with life expectancy \&lt;2 years from randomization
8. Plan to surgery or intervention which needs to stop antiplatelet agents ≥3 months
9. Females with childbearing potential or breast-feeding
10. Conditions that may result in protocol non-compliance by the committees
11. 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
12. Refusal to give written informed consent

Primary outcomes:
measure: Composite of major adverse cardiovascular events (MACE) and major bleeding complications
timeFrame: 2 years
Secondary outcomes:
measure: Target vessel revascularization (TVR), target lesion revascularization (TLR)
timeFrame: 2 years
measure: Stent thrombosis (acute, sub-acute, late, very late)
timeFrame: 2 years
measure: Minor gastrointestinal (GI) complications
timeFrame: 2 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Hyo-Soo Kim, MD, PhD
role: STUDY_CHAIR
References:
citation: Koo BK, Kang J, Park KW, Rhee TM, Yang HM, Won KB, Rha SW, Bae JW, Lee NH, Hur SH, Yoon J, Park TH, Kim BS, Lim SW, Cho YH, Jeon DW, Kim SH, Han JK, Shin ES, Kim HS; HOST-EXAM investigators. Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial. Lancet. 2021 Jun 26;397(10293):2487-2496. doi: 10.1016/S0140-6736(21)01063-1. Epub 2021 May 16.