Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in Subjects With Coronary Artery Lesions (BIOFLOW-VII)

BIOTRONIK - A Prospective Multicenter Study to Confirm the SaFety and Effectiveness of the Orsiro SiroLimus Eluting Coronary Stent System in the Treatment Of Subjects With up to Three De Novo or Restenotic Coronary Artery Lesions - VII

The objective of this post-approval study is to confirm that the clinical performance of the Orsiro stent in a real-world setting is similar to the clinical performance observed for Orsiro in the BIOFLOW-V Investigational Device Exemption pivotal trial, as a condition of the US Food and Drug Administration (FDA) approval (P170030).

Study Overview

• Status: Active, not recruiting
• Conditions: Myocardial Ischemia; Coronary Artery Disease; Angina Pectoris; Acute Coronary Syndrome; Ischemic Heart Disease; Atherosclerosis, Coronary
• Intervention / Treatment: Device: Orsiro DES

Detailed Description

BIOFLOW-VII is a prospective, multicenter, single-arm study. Subjects with coronary artery disease (CAD) who undergo an on-label percutaneous coronary intervention (PCI) with a placed Orsiro stent within the prior 24 hours will be screened post-index procedure per the protocol inclusion and exclusion criteria.

Following the index procedure and study enrollment, subjects will be followed for 5 years. The follow-up schedule will include an intermediate study visit at 1 month, a primary endpoint study visit at 12 months, and long-term study visits at 2, 3, 4, and 5 years.

• Study Type: Observational
• Enrollment (Actual): 556

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Fairhope, Alabama, United States, 36532
      • Cardiology Associates of Mobile
  • California
    • Concord, California, United States, 94520
      • John Muir Medical Center
    • Orange, California, United States, 92868
      • St. Joseph Hospital Orange
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
  • Florida
    • Tampa, Florida, United States, 33613
      • AdventHealth Tampa
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Heart Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Park Ridge, Illinois, United States, 60068
      • Advocate Lutheran General Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46920
      • Ascension St. Vincent Medical Group
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Ascension Via Christi Hospitals
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University Of Kentucky
  • Maine
    • Bangor, Maine, United States, 04401
      • Northern Light Cardiology
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • MedStar Union Memorial Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Saint Michael's Medical Center
  • New York
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
  • Ohio
    • Toledo, Ohio, United States, 43608
      • Mercy Health - St Vincent Medical Center
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • Penn State Health Holy Spirit Medical Center
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Austin, Texas, United States, 78705
      • Seton Medical Center Austin
    • Austin, Texas, United States, 78756
      • Austin Heart
    • Dallas, Texas, United States, 75226
      • Baylor Heart and Vascular Hospital
    • Houston, Texas, United States, 77030
      • UT Health Science Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • Charleston Area Medical Center Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects with coronary artery disease (CAD), including those with diabetes mellitus, with symptomatic heart disease, stable angina, unstable angina, non-ST elevation myocardial infarction or documented silent ischemia due to atherosclerotic lesions in the native coronary arteries with a reference vessel diameter of 2.25 mm to 4.0 mm and a lesion length of ≤ 36 mm.

Description

Inclusion Criteria:

1. Subject is ≥18 years of age.
2. Subject was an acceptable candidate for treatment with a drug eluting stent at the qualifying index procedure, in accordance with the applicable guidelines on percutaneous coronary interventions and manufacturer's Instructions for Use.
3. Subject received at least one Orsiro stent during an index procedure occurring within 24 hours prior to informed consent, as assessed by the end time of procedure. If more than one stent was implanted during the index procedure, all stents were Orsiro stents.
4. Subject is eligible for dual antiplatelet therapy (DAPT) treatment with aspirin plus either clopidogrel, prasugrel, ticagrelor or ticlopidine.
5. Subject is willing to comply with study follow-up requirements.
6. Subject has provided written informed consent as approved by the Institutional Review Board (IRB) of the respective clinical site. Legally authorized representatives are not allowed to consent on a subject's behalf.

Each target lesion/vessel must have met all of the following angiographic criteria from the index procedure for the subject to be eligible for the trial:

1. Subject has up to three target lesions in up to two separate target vessels (two target lesions in one vessel and one target lesion in a separate vessel).
2. Target lesion must be de novo or restenotic lesion in native coronary artery; restenotic lesion must have been treated with a standard PTCA only.
3. Target lesion must be in major coronary artery or branch (target vessel).
4. Target lesion must have angiographic evidence of ≥ 50% and < 100% stenosis (by operator visual estimate). If the target lesion is < 70% stenosed, there should be clinical evidence of ischemia.
5. Target vessel must have a Thrombolysis In Myocardial Infarction (TIMI) flow > 1.
6. Target lesion must be ≤ 36 mm in length by operator visual estimate.
7. Target vessel must have a reference vessel diameter of 2.25-4.0 mm by operator visual estimate.
8. Target lesion must have been treated with a maximum of two overlapping stents.

Exclusion Criteria:

1. Subject had clinical symptoms and/or electrocardiogram (ECG) changes consistent with acute ST elevation MI (STEMI) within 72 hours prior to the index procedure.
2. Subject is pregnant and/or breastfeeding or intends to become pregnant during the duration of the study.
3. 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), silicon carbide, PLLA, sirolimus.
4. Revascularization of any target vessel within 9 months prior to the index procedure or previous PCI of any non-target vessel within 30 days prior to the index procedure or any PCI planned within the next 1 year.
5. Presence of an untreated clinically significant stenosis post-procedure whether treatment is planned or not.
6. Planned surgery within 6 months of index procedure unless DAPT can be maintained throughout the peri-surgical period.
7. History of a stroke or transient ischemic attack (TIA) within 6 months prior to the index procedure.
8. Subject has documented LVEF < 30% prior to consent.
9. Subject is dialysis-dependent.
10. Subject has impaired renal function (blood creatinine > 2.5 mg/dL or 221 μmol/L prior to the index procedure).
11. Subject has leukopenia (i.e. < 3,000 white blood cells/mm3), thrombocytopenia (i.e. < 100,000 platelets/mm3) or thrombocytosis (i.e. > 700,000 platelet/mm3).
12. Any significant concurrent medical diagnosis that would potentially impact DAPT effectiveness or increase thrombotic risk.
13. Subject is receiving chronic anticoagulation (e.g. coumadin, dabigatran, apixaban, rivaroxaban or any other agent).
14. Subject has life expectancy of < 1 year.
15. Subject is participating in an investigational (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 follow-up requirements of this study or does not involve a drug that may confound the interpretation of any relevant clinical events of interest (e.g. investigational DAPT therapy).
16. In the investigator's opinion, subject will not be able to comply with the follow-up requirements.

Subjects will be excluded from the trial if any of the target lesions/vessels met any of the following angiographic criteria during the index procedure:

1. Target lesion was located within or treated through a saphenous vein graft or arterial graft.
2. Target lesion was a restenotic lesion that was previously treated with a bare metal or drug-eluting stent (in-stent restenosis).

3. Target lesion had 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 > 2.0 mm in diameter.
4. Target vessel/lesion was excessively tortuous/angulated or is severely calcified, that would prevent complete inflation of an angioplasty balloon. This assessment should be based on visual estimation.
5. Target vessel had angiographic evidence of thrombus.
6. Target lesion was totally occluded (100% stenosis).
7. Target vessel was treated with brachytherapy any time prior to the index procedure.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Orsiro sirolimus coronary stent system; Intervention with a Orsiro DES.	Device: Orsiro DES; Orsiro is a device/drug combination product composed of two components, a device (coronary stent system including a cobalt chromium stent platform), and a drug product (a formulation of sirolimus) contained in a bioabsorbable polymer coating.; Other Names: Orsiro sirolimus coronary stent system

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Target Lesion Failure (TLF) at 12 Months Post-Index Procedure	TLF is defined as all cardiac death, target vessel Q-wave or non-Q-wave myocardial infarction (MI), or clinically driven target lesion revascularization (TLR).	12-Months

Collaborators and Investigators

• Sponsor: Biotronik, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2020
• Primary Completion (Actual): January 12, 2022
• Study Completion (Anticipated): January 1, 2026

Study Registration Dates

• First Submitted: November 21, 2019
• First Submitted That Met QC Criteria: November 21, 2019
• First Posted (Actual): November 25, 2019

Study Record Updates

• Last Update Posted (Actual): March 3, 2022
• Last Update Submitted That Met QC Criteria: March 1, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Sirolimus; DES; Drug eluting coronary stents; Bioabsorbable polymer
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Coronary Disease; Chest Pain; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Ischemia; Atherosclerosis; Acute Coronary Syndrome; Angina Pectoris; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: BIOFLOW-VII

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Applicable de-identified individual participant data will be made available to achieve aims in approved proposals, including but not limited to sub-analysis or meta-analysis.
• IPD Sharing Time Frame: Beginning no later than 12 months and ending no earlier than 3 years following initial publication of clinical study results.

IPD Sharing Access Criteria

Researchers who provide a methodologically sound proposal for analysis that is not pre-planned or already approved with another researcher. Proposals must be approved by BIOTRONIK and Study Principal Investigator.

Proposals should be directed to BIOTRONIK Clinical Studies (BIOTRONIK Inc., Attn: Clinical Studies, 6024 Jean Road, Lake Oswego, OR 97035; 1-800-547-0394). To gain access, data requesters will need to sign a data use/access agreement.

• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No