BIOTRONIK Orsiro Pre-Marketing Registration (BIOFLOW-VI)

BIOTRONIK-Safety and Clinical PerFormance of the Drug ELuting Orsiro Stent in the Treatment of Subjects With de Novo Coronary Artery Lesions-VI

The clinical investigation is a non-inferiority, multicenter, blinding evaluation, randomized, parallel controlled clinical study enrolling up to 440 subjects. All subjects will be randomized 1:1 to receive the BIOTRONIK Orsiro SES or the Abbott Xience Prime™ EES, in order to evaluate the efficacy and safety of the SES drug eluting stent in the treatment of coronary artery disease.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: Coronary Stent

Detailed Description

Clinical or call follow up visits will take place at 1, 6, 12, 24, 36, 48 and 60 months post procedure. At 9 months (+ 30 days) all subjects will undergo a standard quantitative coronary angiography (QCA) follow up to assess the in-stent LLL as the main efficacious evaluation. Use the major adverse cardiac event (death, myocardial infarction and stent thrombosis) within one year post procedure as the main safety indicators to evaluate the investigational product's safety. The clinical and angiographic data sorting, calculation and statistical analysis will be conducted by an independent data management center and angiographic core laboratory.

• Study Type: Interventional
• Enrollment (Actual): 440
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100032
      • Fuwai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria-Clinical

1. Subject who can understand the investigation's goal has provided written informed consent, and is willing to comply with the study's follow-up requirements.
2. Subject is ≥ 18 years and ≤ 75 years old, male or female without pregnant.
3. Subject is an acceptable candidate for PCI.
4. Subject has clinical evidence of asymptomatic ischemia, stable or unstable angina pectoris or old myocardial infarction.
5. Subject has no contraindication for dual anti-platelet therapy treatment.

Inclusion Criteria-Angiographic

1. Target lesion must be in the major coronary artery or a branch (target vessel).
2. Target lesion must have angiographic evidence of ≥ 70% and < 100% stenosis (by operator's visual estimate).
3. Subject has up to two target lesions (two target lesions in one target vessel, or for each target vessel, it has one target lesion).
4. Target lesion is suitable for drug-eluting stent PCI treatment.
5. Target lesion must be ≤ 36 mm in length by operator's visual estimate, and can be completely covered by one stent.
6. Target vessel must have a reference vessel diameter of 2.25-4.0 mm by operator's visual estimate.
7. Target vessel must have a Thrombolysis In Myocardial Infarction (TIMI) flow ≥ 2.

Exclusion Criteria-Clinical

1. Subject is pregnant and/or breastfeeding or intends to become pregnant during the duration of the study.
2. Subject has clinical symptoms and/or ECG changes consistent with acute ST elevation MI (STEMI) within 7 days prior to the index procedure, including hemodynamically unstable non-STEMI (NSTEMI) subjects.
3. Subject is hemodynamically unstable.
4. Subject is an unacceptable candidate for CABG.
5. Subject has a known allergy to contrast medium that cannot be adequately pre-medicated, or any known allergy to thienopyridine, aspirin, both heparin and bivalirudin, L-605 cobalt-chromium (Co-Cr) alloy or one of its major elements (cobalt, chromium, tungsten and nickel), acrylic, fluoropolymers, silicon carbide, PLLA, sirolimus or everolimus.
6. Previous revascularization of any target or non-target vessel 9 months prior to the index procedure.
7. Planned surgery within 6 months of the index procedure.
8. Planned staged treatment during the index procedure or within 30 days after the index procedure.
9. History of a stroke or transient ischemic attack (TIA) within 12 months prior to the index procedure.
10. Subjects with active bleeding disorders, active coagulopathy, or any other reason, who are ineligible for DAPT.
11. Subject will refuse blood transfusions.
12. Subject has documented severe cardiac failure (over III level of NYHA) or left ventricular ejection fraction (LVEF) ≤ 40% as evaluated by echocardiogram, left ventricular angiography, radionuclide ventriculography or any non-invasive imaging method within 90 days prior to the index procedure.
13. Subject is dialysis-dependent.
14. Subject has impaired renal function (i.e., creatinine > 2.0 mg/dL or 175 μmol/L determined) within 7 days prior to the index procedure.
15. Subject has leukopenia (i.e. WBC < 3.5*10*9/L), thrombocytopenia (plt<100*10*9/L) or thrombocytosis (PLT>350*10*9/L).
16. Subject is receiving chronic anticoagulation (e.g. coumadin, dabigatran, apixaban, rivaroxaban or any other agent).
17. Subject is receiving oral or intravenous immunosuppressive therapy (inhaled steroids are excluded), or has known life-limiting immunosuppressive or autoimmune disease (e.g., human immunodeficiency virus, systemic lupus erythematosus; diabetes mellitus is excluded).
18. Subject has a life expectancy of < 3 years.
19. In the investigator's opinion, subject will not be able to comply with the follow-up requirements.
20. Subject is participating in another (medical device or drug) clinical study. Subjects may be concurrently enrolled in a post-market study, as long as the post-market study device, drug or protocol does not interfere with the investigational treatment or protocol of this study.

Exclusion Criteria-Angiographic

1. Target lesion is located within a saphenous vein graft or arterial graft.

2. Target lesion has any of the following characteristics:

   1. Lesion location is within the left main coronary artery, or within 3 mm of the origin of the left anterior descending (LAD) or left circumflex (LCX).
   2. Involves a side branch of > 2.5 mm in diameter. Note: Lesions within 3 mm of the origin of the right coronary artery may be treated.
3. Target lesion is totally occluded (100% stenosis).
4. Target vessel has angiographic evidence of thrombus.
5. Target vessel/lesion is excessively tortuous/angulated or is severely calcified, preventing complete inflation of an angioplasty balloon.
6. Target vessel was treated with brachytherapy at any time prior to the index procedure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIOTRONIK Orsiro SES; Preparation and percutaneous access should be performed according to the standard hospital practice. Both femoral and radial accesses are accepted. The procedure begins once percutaneous access has been made.Following intracoronary injection of nitroglycerin or isosorbide dinitrate, a baseline angiography of the target vessel must be performed according to the QCA corelab guidelines.The subjects randomized to the experimental arm will be implanted with BIOTRONIK sirolimus eluting coronary stent(Orsiro).	Device: Coronary Stent; Other Names: percutaneous coronary intervention
Active Comparator: Abbott Xience Prime™ EES; Preparation and percutaneous access should be performed according to the standard hospital practice. Both femoral and radial accesses are accepted. The procedure begins once percutaneous access has been made.Following intracoronary injection of nitroglycerin or isosorbide dinitrate, a baseline angiography of the target vessel must be performed according to the QCA corelab guidelines.The subjects randomized to the comparator arm will be implanted with Abbott everolimus eluting coronary stent(Xience Prime™).	Device: Coronary Stent; Other Names: percutaneous coronary intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-stent Late Lumen Loss at 9 Months as Assessed by the Core Laboratory QCA Analysis	QCA data will be provided by an independent core laboratory. A separate report with descriptive statistics will be provided by the core laboratory in accordance with their guidelines. For the primary endpoint, both the lesion and patient level analysis will be done for 9-month in-stent LLL. The analysis on patient level for FAS is considered as main analysis. Other analysis based on lesion level and/or PPS is only for supportive purposes.	At 9 months post procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Main Adverse Cardiac Event (MACE)	Main adverse cardiac event include all-cause death, Q wave or non-Q wave myocardial infarction and clinically driven TLR. The comparison between the two treatment groups for the secondary endpoints will be presented by the same anaysis method as baseline characteristics. The normally distributed quantitative variables will be compared by Student's t-test and the qualititative vairiables which are not normally distributed will be compared by using Wilcoxon sum-rank test.	At 5 years post-procedure
Number of Participants With All-cause Death	The MACEs in the test group included 6 cases of all-cause death.Among them: One subject died from upper gastrointestinal hemorrhage, which had no obvious relation to the operation and device.; Two subjects died from gastric cancer and COVID-19 complicated with respiratory failure respectively, which was unrelated to the operation and device.; One subject died suddenly at home on Day 192 after the baseline operation, with the cause of death unknown.; During the 3-year follow-up, subject family member told that he/she had ever been hospitalized for cardiac failure, but died after invalid rescue. The event was determined as cardiac death, of which the relationship with the operation and device cannot be determined.; During the 3-year follow-up of another subject, his/her family member told that he/she had died. For which his/her family member was reluctant to provide relevant supporting documents, the relationship with the operation and device cannot be determined.	At 5 years post-procedure
Number of Participants With Cardiac Death	Two subjects with Cardica death in test group: One of the patient died of sudden death at home, with the cause of death unknown.The patient participated in the trial on April 15, 2016. He/She was treated in local hospital for chest tightness and syncope in September 2016. He was considered to have rheumatic heart disease, heart failure and cardiogenic syncope. After treatment, he was improved and discharged from hospital and died in October 2016. The possibility of sudden cardiac death caused by ventricular arrhythmia cannot be excluded.; During the 3-year follow-up of a subject, his/her family member told that he/she had ever been hospitalized for cardiac failure, but the subject eventually died after invalid rescue of cardiac failure. As the hospital did not have definite basis for acute myocardial infarction during the event. Therefore, the event was determined as cardiac death, of which the relationship with the operation and device cannot be determined.	At 5 years post-procedure
Number of Participants With Myocardial Infarction	Including Q-wave and Non Q-wave myocardial infarction. The comparison between the two treatment groups for the secondary endpoints will be presented by the same anaysis method as baseline characteristics. The normally distributed quantitative variables will be compared by Student's t-test and the qualititative vairiables which are not normally distributed will be compared by using Wilcoxon sum-rank test.	At 5 years post-procedure
Number of Participants With TVR Myocardial Infarction	Target vessel-related myocardial infarction	At 5 years post-procedure
In-stent Thrombus	During the 5-year clinical follow-up after baseline operation, one stent thrombosis event occurred in the test group. On July 21, 2016, the subject was implanted with the Orsiro Sirolimus-Eluting Coronary Stent System due to coronary heart disease. As the subject developed chest pain again, the coronary angiography reexamination was performed on March 22, 2019. During the operation, the OCT (optical coherence tomography) showed stent thrombosis in the right coronary artery, and then thrombus aspiration was performed. Investigators in the clinical trial center where the subject was enrolled believed that the stent thrombosis identified 972 days after the baseline operation belonged to very late stent thrombosis (VLST). The causes of its occurrence were considered to be related to the stent malapposition caused by insufficient stent expansion during the baseline operation and the possible platelet resistance of the subject.	At 5 years post-procedure
Number of Participants With TLR	Target lesion revascularization	At 5 years post-procedure

Collaborators and Investigators

• Sponsor: Biotronik (Beijing) Medical Device Ltd.
• Investigators: Principal Investigator: Yuejin Yang, Fuwai Hospital; Principal Investigator: Jing Xu, Tianjin Chest Hospital; Principal Investigator: Yaling Han, General Hospital of Shenyang Military Region; Principal Investigator: Bo Yu, The Second Affiliated Hospital of Harbin Medical University; Principal Investigator: Dan Song, Wuhan Asian Heart Hospital; Principal Investigator: Hui Li, Daqing Oilfield General Hospital; Principal Investigator: Ye Zhu, West China Hospital; Principal Investigator: Biao Xu, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School; Principal Investigator: Guosheng Fu, Sir Run Run Shaw Hospital; Principal Investigator: Jian Zhang, TEDA International Cardiovascular Hospital; Principal Investigator: Wen Xie, Teaching Hospital of Chengdu University of T.C.M.

Publications and helpful links

General Publications

• Urban P, Gershlick AH, Guagliumi G, Guyon P, Lotan C, Schofer J, Seth A, Sousa JE, Wijns W, Berge C, Deme M, Stoll HP; e-Cypher Investigators. Safety of coronary sirolimus-eluting stents in daily clinical practice: one-year follow-up of the e-Cypher registry. Circulation. 2006 Mar 21;113(11):1434-41. doi: 10.1161/CIRCULATIONAHA.104.532242. Epub 2006 Mar 13.
• Li C, Yang Y, Han Y, Song D, Xu J, Guan C, Gao R, Garcia-Garcia HM, Waksman R, Xu B; BIOFLOW VI Trial Investigators. Comparison of the Ultrathin Strut, Biodegradable Polymer Sirolimus-eluting Stent With a Durable Polymer Everolimus-eluting Stent in a Chinese Population: The Randomized BIOFLOW VI Trial. Clin Ther. 2020 Apr;42(4):649-660.e9. doi: 10.1016/j.clinthera.2020.02.014. Epub 2020 Apr 5.

Helpful Links

• This link is a PubMed URL that allows you to view an article about the efficacy and safety of high-frequency stimulation in patients with atrial fibrillation: a randomized controlled trial. PubMed is a free resource that supports the search and retrieval

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2015
• Primary Completion (Actual): April 6, 2017
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: August 5, 2016
• First Submitted That Met QC Criteria: August 12, 2016
• First Posted (Estimated): August 18, 2016

Study Record Updates

• Last Update Posted (Actual): March 4, 2024
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: C1207

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No