A First-in-Man Study of IBS

Study Overview
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Brief Summary
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The study is a pilot clinical trial for Sirolimus-eluting Iron Bioresorbable Coronary Scaffold System（IBS）. The main purpose of this study is to evaluate the feasibility, preliminary safety and efficacy of IBS. To provide the basis for subsequent large-scale, multi-center, randomized controlled clinical trials of IBS.

Detailed Description
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A prospective, single-center, First-in-Man trial; Study population: 45 subjects. 45 subjects will be randomly assigned into two cohorts: cohort 1(n=30), cohort 2(n=15) The clinical follow up will be performed in all subjects at 1 month, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years post procedure; The Angiographic, Intra-Vascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT) will be performed at 6 months and 2 years post procedure in cohort 1. The Angiographic, IVUS and OCT will be performed at 1 year and 3 years post procedure in cohort 2. The primary study endpoints: Target lesion failure (TLF) at 6 months post procedure Late Lumen Loss at 6 months post procedure

Official Title
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A First-in-Man Study of Sirolimus-eluting Iron Bioresorbable Coronary Scaffold System (IBS)

Conditions
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Single Coronary Vessel Disease

Intervention / Treatment
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* Device: Sirolimus-eluting Iron Bioresorbable Coronary Scaffold System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients participating in this clinical trial must meet the following criteria: Age of 18-75, males or non pregnancy females; Subject must have evidence of myocardial ischemia (e.g., stable, unstable angina, post-infarct angina or silent ischemia) suitable for elective PCI; One target lesion, and target lesion can be completely covered by a single stent; Target lesion length ≤ 18 mm, target lesion diameter between 3.0 mm to 3.5 mm (visual); Visual assessment of target lesion stenosis ≥70%, TIMI blood flow≥ 1; Subject who understand the purpose of testing, voluntary and informed consent, patients undergoing invasive imaging follow-up. Exclusion Criteria: Patients will be excluded if any of the following conditions apply: General: Within 1 week of any acute myocardial infarction or myocardial enzymes did not return to normal; Implantation of stent in target vessel within 1 year, patients with planned intervention again within six months; Patients who had coronary artery bypass (coronary artery bypass grafting); Patients with contraindications for coronary artery bypass graft surgery; Severe heart failure (NYHA class III and above) or left ventricular ejection fraction<40% (ultrasonic or left ventricular angiography); Preoperative renal function: serum creatinine > 2.0 mg/dl or 177 mu mol/L; receiving hemodialysis; Patients had ischemic stroke half a year before implantation, patients had transient ischemic attack 3 months before implantation, patients have high coagulation tendency judged by investigator or laboratory examination; Bleeding, active gastrointestinal ulcers, brain hemorrhage or subarachnoid hemorrhage, contraindications on antiplatelet agents and anticoagulant therapy; patients would not allow to undergoing antithrombotic therapy; Aspirin, clopidogrel, heparin, contrast agent, poly lactic acid polymer, rapamycin and metal allergies; Patients who have a history of disease related to iron overload or iron disorder, such as hereditary hemochromatosis, etc; The patient's life expectancy is less than 12 months; Patient participated in other drug or medical device study and does not meet the primary study endpoint in clinical trials time frame; Poor compliance and patients unable to complete the study in accordance with the requirements; Patient with heart transplant; The unstable arrhythmia, such as high risk ventricular extra systole and ventricular tachycardia; Cancer needs chemotherapy; Patients of immune suppression, autoimmune diseases, planned or undergoing immunosuppressive therapy; Planning or being receiving long-term anticoagulant therapy, such as heparin, warfarin, etc; With six months for elective surgery requires stop using aspirin and clopidogrel; Blood test prompted platelet count < 100 x 10^9/L, or > 700 x 10^9/L, white blood cells < 3 x 10^9/L, or abnormal liver function (ALT, AST 3 times greater than normal range); Patients with diffuse peripheral vascular disease; cannot use 6F catheter; Patients with valvular surgery in the past. Exclusion criteria by angiography: Chronic total occlusion (TIMI blood flow=0 before implantation) , left main coronary artery lesion, ostial lesion, multiple vessel lesion, branch lesion and bridge lesion which branch vessel diameter ≥ 2.0 mm (if the ostium of branch vessel stenosis >40% or needs balloon predilation); visible thrombus in target vessels; Severe calcified lesions and distorted disease which unable to predilation, lesion not suitable for stent delivery and expansion; In-stent restenosis; Myocardial bridge is involved in target lesion; In order to reach the target lesion, study stent has to go through the previous implanted stent; Predilation balloon can't expand completely in target lesion site, judgment standard for fully expansion as below, patients are excluded when do not meet any item: A.DS% < 40% (visual), highly recommend DS% ≤20% B.TIMI blood flow= class 3 (visual) C.No angiography complications (e.g., distal embolization, lateral branch closed) D.No interlining level NHLBI type D - F E.No continuous chest pain (> 5 minutes), and F.No lower or higher ST segment >5 minutes. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBS implantation<br>Implantation of IBS in patients with coronary artery lesions. All the subjects will be assigned to cohort 1 (n=30) and cohort 2 (n=15). | Device: Sirolimus-eluting Iron Bioresorbable Coronary Scaffold System<br>* Implantation of Sirolimus-eluting Iron Bioresorbable Coronary Scaffold System (IBS)<br>* Other names: IBS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study Device related Composite Endpoint (Target Lesion Failure) | Target Lesion Failure is defined as the composited endpoints of including cardiac death, Target vessel related myocardial infarction (TV-MI) and clinical indicated target lesion revascularization (CI-TLR), also known as MACE (major adverse cardiac events). | 6 months after implantation | 
| Late Lumen Loss | Late Lumen Loss | 6 months after implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immediate Success Rate | Device Success: Successfully transit and release the IBS at target lesion, then withdraw the delivery system. Immediate residual stenosis < 30% and TIMI blood flow is class 3 (visual). Lesion Success: Any method of intervention therapy, the residual stenosis of the target lesion < 30% and TIMI blood flow is class 3(visual). | Immediate post procedure | 
| Clinical Success | Defined as based on lesion success, there is no major adverse cardiac events in the hospitalization period. | Hospitalized period post procedure within 7 days | 
| Performance Evaluation of IBS | 4 class (Excellent, good, general, bad) to evaluate the push ability, performance of through the lesions, performance of cover the lesions, support force, withdraw ability. | Immediate post procedure | 
| Device related Composite Endpoint (DoCE) | Target Lesion Failure, defined as the composited endpoints of including cardiac death, target vessel related myocardial infarction (TV-MI) and clinical indicated target lesion revascularization (CI-TLR). | 1 Month, 1 Year, 2 Years, 3 Years, 4 Years, 5 Years post procedure | 
| Patient related Clinical Composite Endpoint (PoCE) | Including all-cause mortality, all myocardial infarction and any revascularization. | 1 Month, 6 Months, 1 Year, 2 Years, 3 Years, 4 Years, 5 Years post procedure | 
| Stent Thrombosis defined by ARC | Timing (acute, sub-acute, late and very late) Evidence (definite and probable) | Acute (0-24 hours), Subacute (24 hours-30 days), Late (30 days-1 year), Very late (after 1 year) | 
| Thickness of acute stent recoil (mm) | Angiographic Endpoint | Immediate post procedure | 
| In-stent, in-segment, proximal and distal minimum lumen diameter (MLD) | Angiographic Endpoint | Immediate post procedure, 6 months, 1 year, 2 years, 3 years | 
| In-stent, in-segment, proximal and distal percent of diameter stenosis (DS, %) | Angiographic Endpoint | Immediate post procedure, 6 months, 1 year, 2 years, 3 years | 
| In-stent, in-segment, proximal and distal late lumen loss (LLL) | Angiographic Endpoint | 1 year, 2 years, 3 years | 
| In-stent, in-segment, proximal and distal angiographic defined restenosis (ABR) | Angiographic Endpoint | 6 months, 1 year, 2 years, 3 years | 
| Vasomotion | Defined as the average diameter change of lumen diameter before and after using nitroglycerin. | 6 months,1 year, 2 years, 3 years | 
| Analysis of neointimal thickness by OCT | Optical Coherence Tomography Endpoint | Immediate post procedure, 6 months, 1 year, 2 years, 3 years | 
| Analysis of proportion of strut coverage by OCT | Optical Coherence Tomography Endpoint | Immediate post procedure, 6 months, 1 year, 2 years, 3 years | 
| Analysis of incomplete strut apposition by OCT | Optical Coherence Tomography Endpoint | Immediate post procedure, 6 months, 1 year, 2 years, 3 years | 
| Analysis of percentage area obstruction by OCT | Optical Coherence Tomography Endpoint | Immediate post procedure, 6 months, 1 year, 2 years, 3 years | 
| Analysis of healing score by OCT | Optical Coherence Tomography Endpoint | Immediate post procedure, 6 months, 1 year, 2 years, 3 years | 
| Analysis of late recoil by OCT | Optical Coherence Tomography Endpoint | Immediate post procedure, 6 months, 1 year, 2 years, 3 years | 
| Analysis of vessel area by IVUS | Intra-Vascular Ultrasound Endpoint | Immediate post procedure, 6 months, 1 year, 2 years, 3 years | 
| Analysis of lumen area by IVUS | Intra-Vascular Ultrasound Endpoint | Immediate post procedure, 6 months, 1 year, 2 years, 3 years | 
| Analysis of scaffold area by IVUS | Intra-Vascular Ultrasound Endpoint | Immediate post procedure, 6 months, 1 year, 2 years, 3 years | 
| Analysis of neointimal area by IVUS | Intra-Vascular Ultrasound Endpoint | Immediate post procedure, 6 months, 1 year, 2 years, 3 years | 
| Analysis of percentage area obstruction by IVUS | Intra-Vascular Ultrasound Endpoint | Immediate post procedure, 6 months, 1 year, 2 years, 3 years | 
| Analysis of volumetric obstruction by IVUS | Intra-Vascular Ultrasound Endpoint | Immediate post procedure, 6 months, 1 year, 2 years, 3 years | 
| Analysis of late recoil area by IVUS | Intra-Vascular Ultrasound Endpoint | Immediate post procedure, 6 months, 1 year, 2 years, 3 years |