Clinical trial NCT03284255: Bioheart Rapamycin Drug-Eluting Bioresorbable Coronary Stent System Clinical Study
Official title: A Randomized Controlled Trial of the Bioheart Rapamycin Drug-Eluting Bioresorbable Coronary Stent System in Patients With Coronary Artery Disease: BIOHEART-II
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Coronary Artery Disease
Antineoplastic Agents
Keywords: Bioresorbable Vascular Scaffold System
Percutaneous Coronary Intervention
Cardiac Catheterization
Tomography, Optical Coherence
Lead sponsor: Shanghai Bio-heart Biological Technology Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: CCRF Inc., Beijing, China
First posted: 2017-09-15
Enrollment: 431
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The Bioheart Randomized Controlled Trial is a prospective multicentred paralleled study, which will enroll 430 patients and randomized 1:1 to study group and control group. Aim to assess the efficacy and safety of Rapamycin Drug-Eluting Bioresorbable Coronary Stent System compare with XIENCE stent in the treatment of patients with up to two coronary lesions.

Detailed description: This study is a prospective, multicentred randomized controlled trial, planning to enroll 430 subjects and randomize 1:1 to study group and control group.

All subjects will accept clinical evaluation at 1 month, 6 month, 9 month and 1, 2, 3, 4, 5 year post procedure.

All subjects will accept angiographic evaluation at 1 year post procedure, and simutaneously 80 subjects (40 in study group and 40 in control group) will accepted OCT evaluation.

To assess the efficacy and safety, the primary endpoint will be in segment late luminal loss at 1 year post procedure, the secondary endpoint is neointima coverage percentage of stent strut (%) at 1 year post procedure.

Eligibility criteria: Inclusion Criteria:

subjects that participate in this study must fulfill all the following criteria:

general inclusion criteria:

1. Age from 18 to 75 years old, man or non-pregnant woman;
2. Subjects with asymptomatic ischemic evidence, stable or unstable angina, or old myocardial infarction, suitable for selective PCI;
3. Subjects without contraindications of coronary artery bypass grafting (CABG);
4. Subjects are able to understand the purpose of this study, volunteer to participate and sign informed consent, willing to accept invasive imaging follow-up.

Angiographic inclusion criteria:

1. One or two de novo target lesions

   1. If subject has only one target lesion, the second non-target lesion can be treated but this non-target lesion must locate in a different epicardial vessel, and must be treated first and be treated successfully prior to the subjects' randomization.
   2. If there are two target lesions, they must locate in different epicardial vessels and both satisfy the angiographic eligibility criteria.
   3. The definition of epicardial vessels means the left anterior descending artery (LAD), the left circumflex artery (LCX), and the right coronary artery (RCA) and their branches. Thus, for example, the subject must not have lesions requiring treatment in both the LAD and a diagonal branch
2. Target lesion diameter stenosis ≥ 70% (or ≥ 50% simultaneously shall have clinical evidence of myocardial ischemia), and TIMI flow grade ≥1; Target lesion length ≤24mm (visually); target lesion diameter between ≥ 2.5 mm to ≤ 4.00 mm.
3. Each target lesion can be fully covered by one stent.

Exclusion Criteria:

If subjects fulfill any of below criterias, this subject shall be exclude from this study.

general exclusion criteria:

1. Any newly onset acute myocardial infarction within 1 week or, myocardial enzymes does not return to normal level after myocardial infarction;
2. Target lesion has any stents implant history within 1 year or subjects planning to receive percutaneous artery intervention within half one year;
3. Subjects with severe heart failure (≥ grade III NYHA) or left ventricular ejection fraction \<35% (accessed by ultrasound or left ventricular angiography)
4. Preprocedure severe kidney functional damaged: serum creatinine\> 2.0mg /dl (176.8μmol / L) or subject is receiving hemodialysis;
5. Subjects with bleeding tendency, active gastrointestinal ulcers, history of cerebral hemorrhage or history of subarachnoid hemorrhage, history within six months of ischemic stroke, contraindications of anti-platelet agents and anticoagulants treatment, and subjects cannot receive anti-thrombolytic therapy;
6. Hypersensitive or allergic to aspirin, clopidogrel, heparin, contrast agent, polylactic acid polymer， rapamycin;
7. The subject's life expectancy is less than 24 months;
8. Subjects participated in other drug or medical device clinical trial and have not reach the primary endpoint;
9. Investigators determine the subjects' compliance is poor, cannot complete the study as required;
10. Subjects have accepted substantial organ transplant or ready to undergo organ transplant;
11. Subjects have unstable arrhythmia, such as high-risk ventricular premature beats, and ventricular tachycardia;
12. Subjects need to receive chemotherapy because of tumor;
13. Subjects have received or planning to receive coronary or chest radiotherapy;
14. Subjects with Immunosuppressive, autoimmune diseases, are planned or undergoing immunosuppressive therapy;
15. Subjects are planning to receive or are receiving long-term anticoagulation therapy, such as heparin, warfarin and so on;
16. Subjects are planning to accept selective surgery within 6 months, need to discontinue aspirin or clopidogrel;
17. Blood tests showed that the platelet count is less than 100 × 109 / L, or over than 700 × 109 / L, the white blood cells count is less than 3 × 109 / L;
18. Diagnosed or suspected liver disease (such as hepatic cirrhosis);
19. Subjects with diffuse peripheral vascular disease, cannot use 6F catheter.

angiographic exclusion criteria

these exclusion criteria apply to the target or non-target lesion(s), target or non-target vessel(s)

1. Target or non-target lesion(s) located in left main;
2. Subjects with coronary artery triple vessel lesion in LAD, LCX or RCA, all need to be treated.

these exclusion criteria apply to the target lesion(s) or target vessel(s)

1. Target lesion located in left main;
2. Target lesion located in the aorto-ostial of RCA (within 3 mm of the origin of the RCA);
3. Target lesion located within 3 mm of the origin of the LAD and LCX;
4. Lesion involving a bifurcation with a:

   1. Side branch ≥ 2.5 mm in diameter, or
   2. Side branch with diameter stenosis ≥ 50%, or
   3. Side branch requiring protection guide wire, or
   4. Side branch requiring pre-dilatation.
5. Anatomy proximal to or within the lesion that may affect delivery of the Bioheart or XIENCE stent, including:

   1. Extreme angulation (≥ 90°) proximal to or within the target lesion, or
   2. Excessive tortuosity (≥ two 45° angles) proximal to or within the target lesion, or
   3. Moderate or heavy calcification proximal to or within the target lesion
6. Target lesion involves a myocardial bridge.
7. Target vessel contains thrombus as indicated in the angiographic images or IVUS.
8. Prior to the index procedure target vessel has been previously treated with a stent at any time such that the Bioheart or XIENCE stent would need to cross the stent to reach the target lesion.
9. Target vessel has been previously treated with a stent and the target lesion is within 5 mm proximal to a previously treated lesion.
10. Target lesion cannot reach the following outcomes, after the complete balloon pre-dilatation:

    1. Residual (DS %) is \< 40% (per visual estimation), ≤ 20% is strongly recommended;
    2. TIMI Grade-3 flow (per visual estimation);
    3. No angiographic complications (e.g., no-reflow, distal embolization, side branch closure)
    4. No dissections NHLBI grade D-F;
    5. No chest pain lasting \> 5 minutes, and;
    6. No ST depression or elevation lasting \> 5 minutes.

Primary outcomes:
measure: in segment late luminal loss
timeFrame: 1 year post procedure
measure: neointima coverage percentage of stent strut (%)
timeFrame: 1 year post procedure
Secondary outcomes:
measure: device success
timeFrame: immediately post procedure
measure: lesion success
timeFrame: immediately post procedure
measure: clinical success
timeFrame: at 1 month post procedure
measure: Device oriented composite endpoint (DoCE)/target lesion failure (TLF)
timeFrame: at 1, 6, 9 month and1, 2, 3, 4, 5 year post procedure
measure: Patient oriented composite endpoint (PoCE)
timeFrame: at 1, 6, 9 month and1, 2, 3, 4, 5 year post procedure
measure: death
timeFrame: at 1, 6, 9 month and1, 2, 3, 4, 5 year post procedure
measure: myocardial infarction (MI)
timeFrame: at 1, 6, 9 month and1, 2, 3, 4, 5 year post procedure
measure: target lesion revascularization
timeFrame: at 1, 6, 9 month and1, 2, 3, 4, 5 year post procedure
measure: target vessel revascularization
timeFrame: at 1, 6, 9 month and1, 2, 3, 4, 5 year post procedure
measure: any coronary revascularization
timeFrame: at 1, 6, 9 month and1, 2, 3, 4, 5 year post procedure
measure: ARC--defined stent thrombosis
timeFrame: at 1, 6, 9 month and1, 2, 3, 4, 5 year post procedure
Other outcomes:
measure: angiographic endpoints-acute stent recoil
timeFrame: immediately post procedure
measure: angiographic endpoints-late lumen loss (LLL)
timeFrame: immediately and 1 year post procedure
measure: angiographic endpoints-minimal lumen diameter (MLD)
timeFrame: immediately and 1 year post procedure
measure: angiographic endpoints-diameter stenosis (DS),
timeFrame: immediately and 1 year post procedure
measure: angiographic endpoints-angiographic binary restenosis (ABR),
timeFrame: 1 year post procedure
measure: OCT imaging endpoints-Neointimal tissue thickness
timeFrame: 1 year post procedure
measure: OCT imaging endpoints-late acquired stent malapposition
timeFrame: 1 year post procedure
measure: OCT imaging endpoints-Volume obstruction percentage
timeFrame: 1 year post procedure
measure: OCT imaging endpoints-Late stent recoil
timeFrame: 1 year post procedure
measure: OCT imaging endpoints-Neointimal Healing Score
timeFrame: 1 year post procedure
Locations:
city: Beijing
country: China
facility: Beijing Anzhen Hospital Capital Medical University
state: Beijing
city: Beijing
country: China
facility: BeijingChao-YangHospital
state: Beijing
city: Beijing
country: China
facility: Fuwai Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Fuzhou
country: China
facility: Fujian Provincial Hospital
state: Fujian
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The Frist Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Nanning
country: China
facility: The People's Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Zhongshan
country: China
facility: Zhongshan People's Hospital
state: Gunagdong
city: Cangzhou
country: China
facility: Cangzhou Central Hospital
state: Hebei
city: Tangshan
country: China
facility: Tangshan Gongren Hospital
state: Hebei
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Changchun
country: China
facility: The Second Hospital of Jilin University
state: Jilin
city: Dalian
country: China
facility: The First Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Dongfang Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital
state: Shanghai
city: Xi'an
country: China
facility: Tangdu Hospital-Fourth Military Medical University
state: Shanxi
city: Hohhot
country: China
facility: Inner Mongolia Autonomous Region People's Hospital
state: The Inner Mongolia Autonomous Region
city: Tianjin
country: China
facility: Taida International Cardioascular Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital (SRRSH), affiliated with the Zhejiang University School of Medicine
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: Fuwai Hospital Chinese Academy of Medical Sciences (CAMS)
name: Shubin Qiao, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Fuwai Hospital Chinese Academy of Medical Sciences (CAMS)
name: Bo Xu, professor
role: STUDY_CHAIR
References: