Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis - SAfety & EffectiveneSS of Drug-ElUting Stents & Anti-platelet REgimen (HOST-ASSURE)

Seoul National University

Status and phase: Unknown; Phase 4

Conditions: Coronary Heart Disease

Treatments: Device: Zotarolimus-eluting coronary stenting system (ZECSS, Endeavor Resolute); Device: Everolimus-eluting coronary stenting system (EECSS, Promus Element); Drug: Triple anti-platelet therapy (TAT); Drug: Double-dose clopidogrel anti-platelet therapy (DDAT)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01267734

HOST-ASSURE

Details and patient eligibility

About

Objectives

1. To compare the safety and long-term effectiveness of coronary stenting with the new platform Everolimus-Eluting coronary stenting system (EECSS, Promus Element) compared with the Zotarolimus-Eluting coronary stenting system (ZECSS, Endeavor Resolute) in patients with coronary heart disease (CHD)
2. To determine the short-term efficacy and safety of triple anti-platelet therapy (TAT, Aspirin 100mg qd, Clopidogrel 75mg qd and Cilostazol 100mg bid) compared with double-dose clopidogrel dual anti-platelet therapy (DDAT, Aspirin 100mg qd and Clopidogrel 150mg qd) in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES)

Study design Prospective, open-label, 2-by-2 multifactorial, randomized, multicenter trial to test the following in CHD patients

1. Non-inferiority of Promus Element stent compared with Endeavor Resolute stent in reducing target lesion failure (TLF)
2. Non-inferiority of TAT compared with DDAT in reducing net clinical outcome Patients will be randomized in a 2-by-2 factorial manner according to the type of drug eluting stent (EECSS vs. ZECSS) and the type anti-platelet regimen (TAT vs. DDAT). Randomization will also be stratified per presence of DM.

Patient enrollment 3750 patients enrolled at 50 centers in Republic of Korea

Patient follow-up Clinical follow-up will occur at 1, 3, 12, 24, 36 months after the procedure. Angiographical follow-up will be recommended to all participants at 13 months after the procedure. Investigator or designee may conduct follow-up as telephone contacts or office visits.

Primary endpoint

1. Target lesion failure (TLF), defined as a composite of cardiac death, target vessel-related myocardial infarction (MI) and ischemia-driven target lesion revascularization (TLR) up to 12 months for the stent arm
2. Net clinical outcome, defined as a composite of cardiac death, nonfatal MI, CVA and major bleeding by PLATO criteria at 1 month for the anti-platelet arm

Full description

Secondary endpoint

1. Clinical and laboratory endpoint at 1 month All death and cardiac death Myocardial infarction (q wave and non-q wave) Stent thrombosis (definite and possible) CVA (hemorrhagic and non-hemorrhagic) Bleeding (major and minor) VerifyNow ASA and VerifyNow P2Y12
2. Clinical endpoint at 12 months All death and cardiac death Target vessel-related MI and all MI (q wave and non-q wave) Target vessel/lesion revascularization (ischemia-driven and all) Stent thrombosis (definite/possible/probable) Net clinical outcome including bleeding (major and minor) Acute success of procedure (device, lesion and procedure)
3. Angiographic (including IVUS or OCT) endpoint at 13 months In-stent & In-segment late loss In-stent & In-segment % diameter stenosis Angiographic pattern of restenosis Neointimal volume, % neointimal volume and % volume obstruction on IVUS or OCT Degree of stent strut endothelialization on OCT

Enrollment: 3,750 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

General Inclusion Criteria

• Subject must be at least 18 years of age.
• Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving the Promus Element or Endeavor Resolute stents, and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure.
• Subject must have significant lesion (>50% by visual estimate) in any of the coronary arteries, venous or arterial bypass grafts.
• Subject must have evidence of myocardial ischemia (e.g., stable, unstable angina, recent infarction, silent ischemia, positive functional study or a reversible changes in the electrocardiogram (ECG) consistent with ischemia). In subjects with diameter stenosis > 70%, evidence of myocardial ischemia does not have to be documented.

Angiographic Inclusion Criteria

• Target lesion(s) must be located in coronary artery, venous or arterial bypass graft with diameter of ≥ 2.5 mm and ≤ 4.00 mm.
• Target lesion(s) must be amenable for percutaneous coronary intervention.

Exclusion criteria

• The patient has a known hypersensitivity or contraindication to any of the following medications: Heparin, Aspirin, Clopidogrel, Cilostazol, Everolimus, Zotarolimus, Contrast media (Patients with documented sensitivity to contrast media which can be effectively premedicated with steroids and diphenhydramine [e.g. rash] may be enrolled. Those with true anaphylaxis to prior contrast media, however, should not be enrolled.)
• Systemic (intravenous) Everolimus or Zotarolimus use within 12 months.
• Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plan to become pregnant any time after enrollment into this study.
• History of bleeding diathesis, known coagulopathy (including heparin-induced thrombocytopenia), abnormal hemogram (Hb<10g/dL or PLT count <100,000/μL) or will refuse blood transfusions
• Patients with severe LV systolic dysfunction (LVEF<25%) or cardiogenic shock
• Gastrointestinal or genitourinary bleeding within the prior 3 months, or major surgery within 2 months.
• Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance (per site investigator's medical judgment).
• Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period.
• Symptomatic heart failure

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3,750 participants in 4 patient groups

EECSS + DDAT

Experimental group

Description:

Promus Element stent + double-dose clopidogrel anti-platelet therapy

Treatment:

Device: Everolimus-eluting coronary stenting system (EECSS, Promus Element)

Drug: Double-dose clopidogrel anti-platelet therapy (DDAT)

ZECSS + DDAT

Active Comparator group

Description:

Endeavor Resolute stent + double-dose clopidogrel anti-platelet therapy

Treatment:

Drug: Double-dose clopidogrel anti-platelet therapy (DDAT)

Device: Zotarolimus-eluting coronary stenting system (ZECSS, Endeavor Resolute)

EECSS + TAT

Experimental group

Description:

Promus Element stent + triple anti-platelet therapy

Treatment:

Device: Everolimus-eluting coronary stenting system (EECSS, Promus Element)

Drug: Triple anti-platelet therapy (TAT)

ZECSS + TAT

Active Comparator group

Description:

Endeavor Resolute stent + triple anti-platele therapy

Treatment:

Device: Zotarolimus-eluting coronary stenting system (ZECSS, Endeavor Resolute)

Drug: Triple anti-platelet therapy (TAT)