BIOTRONIK Orsiro Pre-Marketing Registration

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02870985

Acronym

BIOFLOW-VI

Enrollment

440

Registered

2016-08-18

Start date

2015-07-14

Completion date

2021-12-31

Last updated

2024-03-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Coronary Artery Disease

Brief summary

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.

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.

Interventions

DEVICECoronary Stent

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
In-stent Late Lumen Loss at 9 Months as Assessed by the Core Laboratory QCA Analysis	At 9 months post procedure	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.

Secondary

Measure	Time frame	Description
Number of Participants With All-cause Death	At 5 years post-procedure	The MACEs in the test group included 6 cases of all-cause death.Among them: 1. One subject died from upper gastrointestinal hemorrhage, which had no obvious relation to the operation and device. 2. Two subjects died from gastric cancer and COVID-19 complicated with respiratory failure respectively, which was unrelated to the operation and device. 3. One subject died suddenly at home on Day 192 after the baseline operation, with the cause of death unknown. 4. 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. 5. 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.
Number of Participants With Cardiac Death	At 5 years post-procedure	Two subjects with Cardica death in test group: 1. 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. 2. 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.
Number of Participants With Myocardial Infarction	At 5 years post-procedure	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.
Number of Participants With Main Adverse Cardiac Event (MACE)	At 5 years post-procedure	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.
In-stent Thrombus	At 5 years post-procedure	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.
Number of Participants With TLR	At 5 years post-procedure	Target lesion revascularization
Number of Participants With TVR Myocardial Infarction	At 5 years post-procedure	Target vessel-related myocardial infarction

Countries

China

Participant flow

Recruitment details

recruitment period: July 2015 - September 2016 totally 11 investigational sites(hospitals) in China

Participants by arm

Arm	Count
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™).	220
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).	220
Total	440

Baseline characteristics

Characteristic	BIOTRONIK Orsiro SES	Total	Abbott Xience Prime™ EES
Age, Continuous	59.05 years STANDARD_DEVIATION 8.48	58.715 years STANDARD_DEVIATION 8.56	58.38 years STANDARD_DEVIATION 8.62
Race and Ethnicity Not Collected	—	0 Participants	—
Region of Enrollment China	220 participants	440 participants	220 participants
Sex: Female, Male Female	60 Participants	138 Participants	78 Participants
Sex: Female, Male Male	160 Participants	302 Participants	142 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	6 / 216	6 / 216
other Total, other adverse events	148 / 216	141 / 216
serious Total, serious adverse events	82 / 216	79 / 216

Outcome results

Primary

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.

Time frame: At 9 months post procedure

Population: There were 220 subjects who conducted the procedure in each group.

Arm	Measure	Value (MEAN)	Dispersion
BIOTRONIK Orsiro SES	In-stent Late Lumen Loss at 9 Months as Assessed by the Core Laboratory QCA Analysis	0.05 mm	Standard Deviation 0.21
Abbott Xience Prime™ EES	In-stent Late Lumen Loss at 9 Months as Assessed by the Core Laboratory QCA Analysis	0.07 mm	Standard Deviation 0.22

Secondary

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.