Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in Subjects With Coronary Artery Lesions

NCT02389946 | Completed Results DMC

• 1 other identifier: BIOFLOW-V
• Study Type: interventional
• Target: 1,334
• Locations: 13 countries
• Sites: 92

Brief Summary

The objective of this study is to assess the safety and efficacy of the Orsiro Sirolimus Eluting Coronary Stent System in the treatment of subjects with up to three native de novo or restenotic (standard PTCA only) coronary artery lesions compared to the Xience coronary stent system.

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Target Lesion Failure (TLF) at 12 Months Post-Index Procedure by Bayesian Estimation

  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

Secondary Outcomes (9)

• Number of Lesions With Device Success

  Hospital Discharge (6-24 hours post-index procedure)

• Number of Lesions With Lesion Success

  Hospital Discharge (6-24 hours post-index procedure)

• Number of Participants With Procedure Success

  Hospital Discharge (6-24 hours post-index procedure)

• Number of Participants With Myocardial Infarction

  Hospital Discharge (6-24 hours post-index procedure), 1, 6, 12 months, 2, 3, 4 and 5 years

• Number of Participants With Myocardial Infarction or Cardiac Death

  Hospital Discharge (6-24 hours post-index procedure), 1, 6, 12 months, 2, 3, 4 and 5 years

Study Arms (2)

Orsiro sirolimus coronary stent system

EXPERIMENTAL

Intervention with a Orsiro DES.

Device: Orsiro DES

Xience everolimus coronary stent system

ACTIVE COMPARATOR

Intervention with a Xience DES.

Device: Xience DES

Interventions

Orsiro DES DEVICE

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.

Also known as: Orsiro sirolimus coronary stent system

Orsiro sirolimus coronary stent system

Xience DES DEVICE

Also known as: Xience everolimus coronary stent system

Xience everolimus coronary stent system

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is ≥18 years or the minimum age required for legal adult consent in the country of enrollment.
• Subject is an acceptable candidate for PCI.
• Subject is an acceptable candidate for CABG.
• Subject has clinical evidence of ischemic heart disease, stable or unstable angina pectoris or documented silent ischemia.
• Subject is eligible for dual anti-platelet therapy treatment with aspirin plus either, clopidogrel, prasugrel, ticagrelor or ticlopidine.
• Subject has provided written informed consent.
• Subject is willing to comply with study follow-up requirements.
• Each target lesion/vessel must meet all of the following angiographic criteria for the subject to be eligible for the trial:
• 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).
• Target lesion must be de novo or restenotic lesion in native coronary artery; restenotic lesion must have been treated with a standard PTCA only.
• Target lesion must be in major coronary artery or branch (target vessel).
• Target lesion must have angiographic evidence of ≥ 50% and \< 100% stenosis (by operator visual estimate). If the target lesion is \< 70% stenosed, clinical evidence of ischemia by positive functional study, CT, electrocardiography, FFR, or post infarct angina.
• TIMI flow \> 1.
• Target lesion must be ≤ 36 mm in length by operator visual estimate.
• Target vessel RVD of 2.25-4.0 mm by operator visual estimate.

You may not qualify if:

• Subject has clinical symptoms and/or electrocardiogram (ECG) changes consistent with acute ST elevation myocardial infarction (STEMI) within 72 hours prior to the index procedure. Hemodynamically stable non-STEMI (NSTEMI) subjects are eligible for study enrollment.
• Subject is hemodynamically unstable.
• Subject is pregnant and/or breastfeeding or intends to become pregnant during the duration of the study.
• 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.
• 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.
• Planned surgery within 6 months of index procedure unless dual antiplatelet therapy can be maintained throughout the peri-surgical period.
• History of a stroke or transient ischemic attack (TIA) within 6 months prior to the index procedure.
• Subjects with active bleeding disorders, active coagulopathy, or any other reason, who are ineligible for DAPT.
• Subject will refuse blood transfusions.
• Subject has documented left ventricular ejection fraction (LVEF) \< 30% within 90 days prior to the index procedure.
• Subject is dialysis-dependent.
• Subject has impaired renal function (i.e., blood creatinine \> 2.5 mg/dL or 221 μmol/L determined within 7 days prior to the index procedure).
• 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).
• Subject is receiving oral or intravenous immunosuppressive therapy (inhaled steroids are permitted), or has known life-limiting immunosuppressive or autoimmune disease (e.g., human immunodeficiency virus, systemic lupus erythematosus; diabetes mellitus is permitted).
• Subject is receiving chronic anticoagulation (e.g. coumadin, dabigatran, apixaban, rivaroxaban or any other agent).

Sponsors & Collaborators

• Biotronik, Inc.: lead
• Biotronik AG: collaborator
• Baim Institute for Clinical Research: collaborator
• Medstar Health Research Institute: collaborator

Study Sites (92)

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Fairhope, Alabama, 36535, United States

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Concord, California, 94520, United States

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La Mesa, California, 91942, United States

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Laguna Hills, California, 92653, United States

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Mission Viejo, California, 92691, United States

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Washington D.C., District of Columbia, 20010, United States

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Clearwater, Florida, 33756, United States

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Hollywood, Florida, 33021, United States

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Orlando, Florida, 32803, United States

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Tampa, Florida, 33613, United States

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Atlanta, Georgia, 30309, United States

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Urbana, Illinois, 61801, United States

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Fort Wayne, Indiana, 46845, United States

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Baltimore, Maryland, 21218, United States

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Boston, Massachusetts, 02120, United States

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Bay City, Michigan, 48708, United States

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Detroit, Michigan, 48236, United States

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Lansing, Michigan, 48912, United States

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Pontiac, Michigan, 48341, United States

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Rochester, Michigan, 48307, United States

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Troy, Michigan, 48085, United States

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Ypsilanti, Michigan, 48197, United States

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Minneapolis, Minnesota, 55407, United States

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Omaha, Nebraska, 68124, United States

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Hackensack, New Jersey, 07601, United States

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Neptune City, New Jersey, 07753, United States

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Newark, New Jersey, 07102, United States

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New York, New York, 10021, United States

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New York, New York, 10029, United States

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New York, New York, 10032, United States

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Asheville, North Carolina, 28803, United States

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Greensboro, North Carolina, 27401, United States

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Fargo, North Dakota, 58102, United States

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Cincinnati, Ohio, 45219, United States

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Cleveland, Ohio, 44111, United States

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Columbus, Ohio, 43210, United States

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Elyria, Ohio, 44035, United States

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Toledo, Ohio, 43606, United States

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Toledo, Ohio, 43608, United States

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Portland, Oregon, 97225, United States

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Butler, Pennsylvania, 16001, United States

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Mechanicsburg, Pennsylvania, 17050, United States

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Wynnewood, Pennsylvania, 19096, United States

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York, Pennsylvania, 17403, United States

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Providence, Rhode Island, 02906, United States

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Greenville, South Carolina, 29605, United States

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Rock Hill, South Carolina, 29732, United States

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Knoxville, Tennessee, 37934, United States

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Dallas, Texas, 75226, United States

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Houston, Texas, 77030, United States

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McKinney, Texas, 75069, United States

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Tyler, Texas, 75701, United States

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Charlottesville, Virginia, 22908, United States

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Virginia Beach, Virginia, 23454, United States

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Charleston, West Virginia, 25304, United States

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Adelaide, SA 5011, Australia

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Genk, 3600, Belgium

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Leuven, 3000, Belgium

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Roeselare, 8800, Belgium

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Calgary, Alberta, T2N 4Z6, Canada

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Aarhus, 8200, Denmark

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Bad Segeberg, 23795, Germany

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Berlin, 10249, Germany

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Berlin, 10967, Germany

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Hamburg, 20246, Germany

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Minden, 32429, Germany

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Neuss, 41464, Germany

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Budapest, 1085, Hungary

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Pécs, 7624, Hungary

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Szeged, 6720, Hungary

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Haifa, 31096, Israel

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Jerusalem, 91120, Israel

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Petah Tikva, 49101, Israel

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Rehovot, 76100, Israel

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Tel Aviv, 64239, Israel

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Breda, 4818 CK, Netherlands

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Eindhoven, 5623 EJ, Netherlands

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Nieuwegein, 3435 CM, Netherlands

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Auckland, 1142, New Zealand

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Daegu, 705-718, South Korea

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Gwangju, 501-757, South Korea

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Seoul, 110-744, South Korea

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Seoul, 135-720, South Korea

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Seoul, 137-701, South Korea

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Barcelona, 08036, Spain

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Barcelona, 08907, Spain

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Madrid, 28222, Spain

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Málaga, 29010, Spain

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Seville, 41071, Spain

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Lausanne, 1011, Switzerland

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Zurich, 8063, Switzerland

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Zurich, 8091, Switzerland

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Related Publications (13)

• Doros G, Massaro JM, Kandzari DE, Waksman R, Koolen JJ, Cutlip DE, Mauri L. Rationale of a novel study design for the BIOFLOW V study, a prospective, randomized multicenter study to assess the safety and efficacy of the Orsiro sirolimus-eluting coronary stent system using a Bayesian approach. Am Heart J. 2017 Nov;193:35-45. doi: 10.1016/j.ahj.2017.08.001. Epub 2017 Aug 5.

  PMID: 29129253 BACKGROUND

• Kandzari DE, Mauri L, Koolen JJ, Massaro JM, Doros G, Garcia-Garcia HM, Bennett J, Roguin A, Gharib EG, Cutlip DE, Waksman R; BIOFLOW V Investigators. Ultrathin, bioresorbable polymer sirolimus-eluting stents versus thin, durable polymer everolimus-eluting stents in patients undergoing coronary revascularisation (BIOFLOW V): a randomised trial. Lancet. 2017 Oct 21;390(10105):1843-1852. doi: 10.1016/S0140-6736(17)32249-3. Epub 2017 Aug 26.

  PMID: 28851504 RESULT

• Kandzari DE, Koolen JJ, Doros G, Massaro JJ, Garcia-Garcia HM, Bennett J, Roguin A, Gharib EG, Cutlip DE, Waksman R; BIOFLOW V Investigators. Ultrathin Bioresorbable Polymer Sirolimus-Eluting Stents Versus Thin Durable Polymer Everolimus-Eluting Stents. J Am Coll Cardiol. 2018 Dec 25;72(25):3287-3297. doi: 10.1016/j.jacc.2018.09.019. Epub 2018 Sep 23.

  PMID: 30257191 RESULT

• Roguin A, Kandzari DE, Marcusohn E, Koolen JJ, Doros G, Massaro JM, Garcia-Garcia HM, Bennett J, Gharib EG, Cutlip DE, Waksman R. Subgroup Analysis Comparing Ultrathin, Bioresorbable Polymer Sirolimus-Eluting Stents Versus Thin, Durable Polymer Everolimus-Eluting Stents in Acute Coronary Syndrome Patients. Circ Cardiovasc Interv. 2018 Oct;11(10):e007331. doi: 10.1161/CIRCINTERVENTIONS.118.007331.

  PMID: 30354631 RESULT

• Mankerious N, Toelg R, Abdelghani M, Garcia-Garcia HM, Farhan S, Allali A, Windecker S, Lefevre T, Saito S, Kandzari DE, Waksman R, Richardt G, Hemetsberger R. Impact of coronary artery tortuosity on outcomes following stenting with newer-generation drug-eluting stents. An analysis of the randomized BIOFLOW trials. Rev Esp Cardiol (Engl Ed). 2025 Aug;78(8):682-691. doi: 10.1016/j.rec.2024.12.009. Epub 2025 Jan 4. English, Spanish.

  PMID: 39761745 DERIVED

• Hemetsberger R, Mankerious N, Toelg R, Abdelghani M, Farhan S, Garcia-Garica HM, Allali A, Windecker S, Lefevre T, Saito S, Kandzari D, Waksman R, Richardt G. Patients with higher-atherothrombotic risk vs. lower-atherothrombotic risk undergoing coronary intervention with newer-generation drug-eluting stents: an analysis from the randomized BIOFLOW trials. Clin Res Cardiol. 2023 Sep;112(9):1278-1287. doi: 10.1007/s00392-023-02205-4. Epub 2023 Apr 16.

  PMID: 37062047 DERIVED

• Hemetsberger R, Abdelghani M, Toelg R, Garcia-Garcia HM, Farhan S, Mankerious N, Elbasha K, Allali A, Windecker S, Lefevre T, Saito S, Kandzari D, Waksman R, Richardt G. Complex vs. non-complex percutaneous coronary intervention with newer-generation drug-eluting stents: an analysis from the randomized BIOFLOW trials. Clin Res Cardiol. 2022 Jul;111(7):795-805. doi: 10.1007/s00392-022-01994-4. Epub 2022 Feb 25.

  PMID: 35212802 DERIVED

• Hemetsberger R, Abdelghani M, Toelg R, Mankerious N, Allali A, Garcia-Garcia HM, Windecker S, Lefevre T, Saito S, Slagboom T, Kandzari D, Koolen J, Waksman R, Richardt G. Impact of Coronary Calcification on Clinical Outcomes After Implantation of Newer-Generation Drug-Eluting Stents. J Am Heart Assoc. 2021 Jun 15;10(12):e019815. doi: 10.1161/JAHA.120.019815. Epub 2021 May 29.

  PMID: 34056911 DERIVED

• Dan K, Garcia-Garcia HM, Kolm P, Windecker S, Saito S, Kandzari DE, Waksman R. Comparison of Ultrathin, Bioresorbable-Polymer Sirolimus-Eluting Stents and Thin, Durable-Polymer Everolimus-Eluting Stents in Calcified or Small Vessel Lesions. Circ Cardiovasc Interv. 2020 Sep;13(9):e009189. doi: 10.1161/CIRCINTERVENTIONS.120.009189. Epub 2020 Sep 8.

  PMID: 32895004 DERIVED

• Toelg R, Slagboom T, Waltenberger J, Lefevre T, Saito S, Kandzari DE, Koolen J, Richardt G. Individual patient data analysis of the BIOFLOW study program comparing safety and efficacy of a bioresorbable polymer sirolimus eluting stent to a durable polymer everolimus eluting stent. Catheter Cardiovasc Interv. 2021 Nov 1;98(5):848-856. doi: 10.1002/ccd.29254. Epub 2020 Sep 5.

  PMID: 32890442 DERIVED

• Kandzari DE, Koolen JJ, Doros G, Garcia-Garcia HM, Bennett J, Roguin A, Gharib EG, Cutlip DE, Waksman R; BIOFLOW V Investigators. Ultrathin Bioresorbable-Polymer Sirolimus-Eluting Stents Versus Thin Durable-Polymer Everolimus-Eluting Stents for Coronary Revascularization: 3-Year Outcomes From the Randomized BIOFLOW V Trial. JACC Cardiovasc Interv. 2020 Jun 8;13(11):1343-1353. doi: 10.1016/j.jcin.2020.02.019.

  PMID: 32499026 DERIVED

• Mattke S, Hanson M, Bentele M, Kandzari DE. Cost and Mortality Implications of Lower Event Rates After Implantation of an Ultrathin-Strut Coronary Stent Compared With a Thin-Strut Stent Over Four Years. Cardiovasc Revasc Med. 2020 Jul;21(7):835-842. doi: 10.1016/j.carrev.2019.12.018. Epub 2019 Dec 18.

  PMID: 31954661 DERIVED

• Mattke S, Hanson M, Dallmann AC, Bentele M. Health Economic Evaluation of an Ultrathin, Bioresorbable-Polymer Sirolimus-Eluting Coronary Stent Compared to a Thin, Durable-Polymer Everolimus-Eluting Stent. Cardiovasc Revasc Med. 2019 Sep;20(9):752-757. doi: 10.1016/j.carrev.2018.11.006. Epub 2018 Nov 20.

  PMID: 30638888 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Myocardial Ischemia; Acute Coronary Syndrome; Angina Pectoris

Condition Hierarchy (Ancestors)

Coronary Disease; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Amy Culley, Director of Vascular Intervention Clinical Studies
• Organization: BIOTRONIK, Inc

amy.culley@biotronik.com

503-451-8034

Study Officials

• Ron Waksman, MD

  Medstar Health Research Institute

  STUDY CHAIR

• David Kandzari, MD

  Piedmont Heart Institute

  PRINCIPAL INVESTIGATOR

• Jacques Koolen, MD

  Catharina Ziekenhuis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: March 17, 2015
• Study Start: May 1, 2015
• Primary Completion: April 1, 2017
• Study Completion: March 1, 2021
• Last Updated: August 3, 2022
• Results First Posted: August 1, 2019

Record last verified: 2022-08

Locations

BE (3); US (55); NL (3); KR (5); AU (1); IL (5); DE (6); CA (1); DK (1); HU (3); NZ (1); ES (5); CH (3)