A First-in-Man Study to Evaluate the Feasibility and Safety of Sirolimus-eluting Iron Bioresorbable Coronary Scaffold System

Study Overview
=================
Brief Summary
-----------------
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
-----------------
A prospective, non-randomized trial Study population: 15 patients Clinical follow up will be required at postoperative, 1 month, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years; All the subjects perform the angiography, Intra-vascular ultrasound (IVUS) and Optical coherence tomography (OCT) at 1 year and 3 years. The primary study endpoint is target lesion failure (TLF) at 1 month post procedure; and imaging findings as the secondary study endpoint. To evaluate the feasibility, safety and performance of IBS.

Official Title
-----------------
A Prospective, Non-randomized, Open-label, Non-comparative, First-in-Man Study to Evaluate the Feasibility and Safety of Sirolimus-eluting Iron Bioresorbable Coronary Scaffold System

Conditions
-----------------
Single Coronary Vessel Disease

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


Participation Criteria
=================
Eligibility Criteria
-----------------
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 performed 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 have ischemic stroke half a year before implantation, patients have 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 109/L, or > 700 x 109/L, white blood cells < 3 x 109/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
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: 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. | Device: Device: Sirolimus-eluting Iron Bioresorbable Coronary Scaffold System<br>* Implantation of Sirolimus-eluting Iron Bioresorbable Coronary Scaffold System (IBS)<br>|

What is the study measuring?
-----------------
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). | 1 month 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 postoperative | 
| Clinical Success | Defined as based on lesion success, there is no major adverse cardiac events in the hospitalization period. | Hospitalized period postoperative 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 postoperative | 
| 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), also known as MACE (major adverse cardiac events). | 6 Month, 1 Year, 2 Years, 3 Years, 4 Years, 5 Years postprocedure | 
| Patient related Clinical Composite Endpoint (PoCE) | Including all-cause mortality, all myocardial infarction and target lesion revascularization. | 30 Days, 6 Months, 1 Year, 2 Years, 3 Years, 4 Years, 5 Years postprocedure | 
| 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) | 
| Acute stent retraction | Angiographic Endpoint | Immediate postoperative | 
| In-stent, in-segment, proximal and distal minimum lumen diameter (MLD) | Angiographic Endpoint | Immediate postoperative, 1 year, 3 years | 
| In-stent, in-segment, proximal and distal Diameter stenosis(DS) | Angiographic Endpoint | 1 year, 3 years | 
| In-stent, in-segment, proximal and distal Late lumen loss (LLL) | Angiographic Endpoint | 1 year, 3 years | 
| In-stent, in-segment, proximal and distal Angiographic defined restenosis (ABR) | Angiographic Endpoint | 1 year, 3 years | 
| Vasomotion | Defined as the average diameter change of lumen diameter before and after using nitroglycerin. | 1 year, 3 years | 
| Analysis of Morphometric, lesion composition and scaffold strut data obtained with OCT | Optical Coherence Tomography Endpoint | : Immediate postoperative, 1 year, 3 years | 
| Analysis of Vascular and scaffold morphology obtained with IVUS | Intra-Vascular Ultrasound Endpoint | Immediate postoperative,1 year, 3 years |