Clinical trial NCT04175626: Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in Subjects With Coronary Artery Lesions
Official title: 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
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Coronary Artery Disease
Atherosclerosis, Coronary
Myocardial Ischemia
Ischemic Heart Disease
Acute Coronary Syndrome
Angina Pectoris
Keywords: Drug eluting coronary stents
Sirolimus
Bioabsorbable polymer
DES
Lead sponsor: Biotronik, Inc.
Sponsor class: INDUSTRY
First posted: 2019-11-25
Enrollment: 556
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Target Lesion Failure (TLF) at 12 Months Post-Index Procedure
timeFrame: 12-Months
Secondary outcomes:
measure: All-cause Death
timeFrame: at Hospital Discharge an average of 1 day, at 1 Month, at 1 Year
measure: Protocol-defined Any-vessel Myocardial Infarction
timeFrame: at Hospital Discharge an average of 1 day, at 1 Month, at 1 Year
measure: Target Lesion Revascularization (TLR)
timeFrame: at Hospital Discharge an average of 1 day, at 1 Month, at 1 Year
measure: Target Vessel Revascularization (TVR)
timeFrame: at Hospital Discharge an average of 1 day, at 1 Month, at 1 Year
measure: Cardiac Death or Protocol-defined Any-vessel MI
timeFrame: at Hospital Discharge an average of 1 day, at 1 Month, at 1 Year
measure: Target Lesion Failure (Cardiac Death, Protocol-defined Target Vessel MI, Clinically-driven TLR)
timeFrame: at Hospital Discharge an average of 1 day, at 1 Month, at 1 Year
measure: Target Vessel Failure (Cardiac Death, Protocol-defined Target Vessel MI, Clinically-driven TVR)
timeFrame: at Hospital Discharge an average of 1 day, at 1 Month, at 1 Year
measure: MACE (Death, Protocol-defined Any Vessel Q Wave or Non-Q Wave MI, Clinically-driven TLR
timeFrame: at Hospital Discharge an average of 1 day, at 1 Month, at 1 Year
measure: Stent Thrombosis
timeFrame: at 24 Hours, at 1 Month, at 1 Year
measure: Number of Lesions With Device Success
timeFrame: at Hospital Discharge an average of 1 day
measure: Number of Lesions With Lesion Success
timeFrame: at Hospital Discharge an average of 1 day
measure: Number of Participants With Procedure Success
timeFrame: at Hospital Discharge an average of 1 day
Other outcomes:
Locations:
city: Fairhope
country: United States
facility: Cardiology Associates of Mobile
state: Alabama
city: Concord
country: United States
facility: John Muir Medical Center
state: California
city: Orange
country: United States
facility: St. Joseph Hospital Orange
state: California
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Tampa
country: United States
facility: AdventHealth Tampa
state: Florida
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Ascension St. Vincent Medical Group
state: Indiana
city: Wichita
country: United States
facility: Ascension Via Christi Hospitals
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Bangor
country: United States
facility: Northern Light Cardiology
state: Maine
city: Baltimore
country: United States
facility: MedStar Union Memorial Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Toledo
country: United States
facility: Mercy Health - St Vincent Medical Center
state: Ohio
city: Camp Hill
country: United States
facility: Penn State Health Holy Spirit Medical Center
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Health
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Seton Medical Center Austin
state: Texas
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Dallas
country: United States
facility: Baylor Heart and Vascular Hospital
state: Texas
city: Houston
country: United States
facility: UT Health Science Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Charleston
country: United States
facility: Charleston Area Medical Center Memorial Hospital
state: West Virginia
Study officials:
affiliation: Piedmont Heart Institute
name: David Kandzari, MD
role: PRINCIPAL_INVESTIGATOR
References: