Revolution™ Peripheral Atherectomy System for Lower Extremity Peripheral Arterial Revascularization

To evaluate the safety and effectiveness of the Revolution™ Peripheral Atherectomy System in the treatment of infrainguinal lower extremity peripheral arterial occlusive disease.

This Atherectomy system will be used on eligible patients with stenosis of at least 70% diameter reduction to evaluate the change in stenosis after the procedure (effectiveness) and the presence of any major adverse events (safety) for up to 30 days after the procedure.

This study intends to enroll up to 121 subjects at up to 18 investigational sites in the United States. This is a single-arm study of the Revolution™ Peripheral Atherectomy System in subjects with peripheral arterial disease (PAD).

The primary safety endpoint is freedom from 30-day Major Adverse Events (MAE), defined as the composite of all-cause mortality, clinically-driven target lesion revascularization (TLR), major target limb amputation, major target vessel perforation requiring surgical or endovascular repair and clinically-significant distal embolization in the target limb; as adjudicated by the independent Clinical Events Committee (CEC).

The primary effectiveness endpoint is technical success, defined by ≤50% diameter stenosis after atherectomy with the Revolution™ Peripheral Atherectomy System and prior to adjunctive therapy, as measured by the independent core laboratory on the post-atherectomy contrast angiogram. Effectiveness will be assessed for investigator-identified target lesions and will be calculated as a binary variable as the proportion of target lesions with technical success.

The following will be assessed as secondary endpoints of the study:

1. Change in % stenosis after treatment with Revolution™ Peripheral Atherectomy System, determined after atherectomy and prior to other adjunctive therapies, as measured by the angiographic core laboratory.
2. Procedural success as defined by target lesion residual stenosis of \<30% at the conclusion of the index procedure, after atherectomy and any adjunctive endovascular treatment, as measured by the angiographic core laboratory.
3. Assessment of the individual components of the primary safety endpoint (MAE); including all-cause mortality, major target limb amputation, clinically significant distal embolization, major target vessel perforation requiring surgical or endovascular repair, and clinically-driven TLR, measured through 30 days and at 6 months.
4. Minor unplanned target limb amputation rate through 30 days and 6 months;
5. Myocardial infarction through 30 days and 6 months;
6. Incidence of target vessel revascularization (TVR) through 30 days and 6 months;
7. Frequency of angiographic procedural distal embolization (symptomatic) in the target limb as confirmed angiographically by the core laboratory;
8. Primary patency of the target lesion at 30 days and 6 months, determined by duplex ultrasound or angiography;
9. Primary-assisted patency of the target lesion at 30 days and 6 months, determined by duplex ultrasound or angiography;
10. Secondary patency of the target lesion at 30 days and 6 months, determined by duplex ultrasound or angiography.

Subjects with symptomatic PAD eligible for treatment with the Revolution™ Peripheral Atherectomy System with atherosclerotic lesions of the superficial femoral, popliteal and tibial arteries will be eligible for inclusion in the study.

A performance goal of 80% for safety and 76% for effectiveness has been established from prior studies. Enrollment of 121 subjects will provide 90% power, based upon a one-sided 97.5% exact binomial test, an anticipated 30-day MAE rate of 9%, acute technical success of 86%, and a 30-day attrition rate of approximately 10%.

The regulatory submission will be based on an approximate sample size of 121 subjects. Assuming a lesion-to-subject ratio of 1.5, approximately 165 target lesions will be evaluable for the primary effectiveness endpoint. Subset analyses will be performed for device effectiveness for superficial femoral/popliteal and tibial artery target lesions.

Pre-Enrollment procedures include testing, reviewing Medical history, physical examination with vital signs and directed peripheral vascular examination, laboratory assessment, ankle-brachial or toe-brachial index, and patient-reported outcome measures. The diagnostic angiogram at time of the planned index procedure is performed prior to the point of enrollment in the study; eligibility is, in part, based upon the anatomic findings of the angiogram.

Subjects will have required follow-up evaluations at the following time points:

1. Discharge;
2. 1 month post index procedure;
3. 6 months post index procedure;

Follow-Up Data Collection:

1. Adverse Events at the index procedure, hospital discharge, and through 6 months;
2. Rutherford Classification at 1 and 6 months;
3. Ankle-brachial or toe-brachial index at 1 and 6 months;
4. Duplex ultrasound of the target vessel at 1 and 6 months.

An independent Clinical Events Committee (CEC) will review all primary safety endpoint events, unanticipated adverse device effects, and other important safety occurrences as specified in the CEC Charter. Additionally, an independent Data Safety Monitoring Board (DSMB) will review safety data from the study at predetermined time points and as deemed necessary by the Sponsor or the DSMB Chair. The DSMB will make recommendations on protocol modifications and continuation of the study.

Eligibility Criteria:
Inclusion Criteria:

1. Age ≥ 18 years;
2. Willing and able to provide informed consent.
3. Ability to take at least one form of anti-platelet therapy.
4. Rutherford categories 2 to 5 in the target limb.
5. Lesions to be treated with the study device must be located in the same limb.
6. Target lesion(s) located within the superficial femoral, popliteal or tibial arteries.
7. Target lesion(s) with stenosis ≥70% diameter reduction as measured by site-reported angiography.
8. Target lesion length(s) ≤150 mm.
9. Target lesions(s) with reference vessel diameter (proximal and distal to target lesion) ≥2.0 mm and ≤4.0 mm.

Exclusion Criteria:

1. Subjects in whom amputation above the ankle is necessary, irrespective of the success of revascularization.
2. In-stent restenosis within the target lesion.
3. Flow-limiting dissection, Type C or greater.
4. Target lesions within an autogenous or prosthetic bypass graft.
5. History of an endovascular procedure or open vascular reconstruction in the index limb within the last 30 days, including thrombolytic therapy.
6. Any open vascular surgical procedure planned in the target limb or endovascular procedures planned in the target vessel within 30 days after the index procedure.
7. Kidney disease of sufficient severity, in the Investigator's opinion, to contraindicate lower extremity angiography using standard or alternate contrast agents as per the local Standard of Care.
8. Pregnancy or breast feeding. A woman of child-bearing potential must have a negative pregnancy test within one week of index procedure.
9. Myocardial infarction or stroke within 2 months of enrollment.
10. Contraindication to antiplatelet, anticoagulant, or thrombolytic therapy.
11. Uncorrectable bleeding diathesis, platelet dysfunction, thrombocytopenia with platelet count \< 125,000/μL, known coagulopathy, or INR \> 1.5.
12. Known allergy to contrast agents or medications used to perform endovascular intervention that cannot be adequately pretreated in the opinion of the investigator.
13. History of heparin-induced thrombocytopenia.
14. Psychiatric disorder which, according to the investigator, has potential to interfere with provision of informed consent, completion of tests, therapy, or follow-up.
15. Clinical/angiographic evidence of distal embolization or acute thrombus.
16. Significant stenosis (\>50% diameter reduction) or occlusion of inflow vessels that was not successfully treated (\<50% residual stenosis without flow limiting dissection) before the study intervention.