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

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).

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.

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.