JetStream Atherectomy for the Treatment of In-stent Restenosis

Study Overview
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Brief Summary
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The purpose of this study is to test the hypothesis that Jetstream atherectomy (JS) and adjunctive balloon angioplasty (PTA) (JS +PTA) improves target lesion revascularization (TLR) at 6 months follow-up when compared to historic data from PTA alone in the treatment of femoropopliteal (FP) arterial In-stent restenotic (ISR) disease. This is a prospective, multicenter, single arm study evaluating the investigational use of Jetstream Atherectomy (JS) and adjunctive balloon angioplasty (JS +PTA) in the treatment of FP ISR lesions in subjects with claudication or limb ischemia (Rutherford clinical category (RCC) of 2-4) (lesion length ≥ 4 cm). The comparator arm is historic data from plain old balloon angioplasty derived from a Meta-analysis of the 3 published randomized trials in the field.

Detailed Description
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The Boston Scientific Jetstream XC catheter is a rotating, aspirating, expandable catheter for active removal of atherosclerotic disease and thrombus in peripheral vasculature. The JS XC System has been cleared by the Food and Drug Administration (FDA) for use in the peripheral vasculature to treat denovo and non-stent infrainguinal lesions Several studies have shown that stenting of the FP artery leads to higher long term patency. Bare metal stents however have not shown conclusively to reducemTLR which is in contrast to drug coated balloons (DCB) and drug coated stents (DCS). Irrespective, stenting has several disadvantages including a continued high rate of restenosis and stent fractures that is progressive with time. FP ISR occurs in more than one third of patients at 1 year and up to 49% at 2 years. Complex lesions (long, Trans-Atlantic Inter-Society Consensus II C/D lesions, total occlusions), certain demographics (female gender, diabetes mellitus), critical limb ischemia and significant stent fractures are associated with a higher rate of restenosis. Also the majority of occluded stents are restenotic-thrombotic and generally are more challenging to treat. Recently 3 randomized trials were presented in treating FP ISR; the EXCImer Laser Randomized Controlled Study for Treatment of FemoropopliTEal In-Stent Restenosis (EXCITE ISR) trial (randomized laser + PTA vs PTA alone), the RELINE trial (Propaten Bioactive Surface vs. standard balloon angioplasty for treatment of in-stent restenosis in the superficial femoral artery) and the Randomized Femoral Artery In-Stent Restenosis (FAIR) Trial. All these studies showed superiority over PTA in treating FP ISR. Early animal data (porcine model of FP ISR) and feasibility human data (JetStream ISR study) have shown that the JetStream device is effective in ablating restenotic tissue within restenotic FP stents and had no safety concerns within well apposed stents and in the absence of Class III and IV fractures. The purpose of this study is to assess and estimate the effect of treating FP ISR with plaque excision using JS in combination with adjunctive PTA and compare this to historic control of PTA. The comparator arm is historic data from PTA derived from a study-level meta-analysis of the 3 published randomized trials in the field.

Official Title
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JetStream Atherectomy for the Treatment of In-stent Restenosis of the Femoropopliteal Artery

Conditions
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Femoropopliteal In-stent Restenosis

Intervention / Treatment
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* Device: JetStream XC with balloon angioplasty


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with symptomatic peripheral arterial disease (Rutherford Becker Class II to IV) Previously treated with stenting in the femoropopliteal segment No limit on how many times the target in-stent restenotic lesion has been previously treated. There is no exclusion based on how the prior treatment was done including if drug eluting balloons or stents have been used. Covered stents cannot be included There is no limit on the length of the target lesion as long as only one target lesion is treated and enrolled Exclusion Criteria: Subjects must meet all of the following criteria to be eligible to participate in this study: Subject is 18 years of age or older. Subject presents with clinical evidence of peripheral arterial disease with ISR in the femoropopliteal segment (includes common femoral, superficial femoral and popliteal) Subject presents with a Rutherford Classification of 2-4 and has symptoms of rest limb pain or claudication. Target lesion(s) must be viewed angiographically and have ≥50% stenosis. The atherectomy wire must be placed entirely across all lesions to be treated with no visible evidence of clear or suspected subintimal/substent wire passage. The main target vessel reference diameter must be > or = 5 mm and ≤ 7 mm One patent distal run-off vessel with <70% disease and with brisk flow is required. Intraluminal crossing of the lesion. If this is not certain, IVUS may be used to verify this per operator's discretion Patient has signed approved informed consent. Patient is willing to comply with the follow-up evaluations at specified times.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JetStream XC with balloon angioplasty<br>The intervention consists of JetStream atherectomy of femoropopliteal in-stent restenosis using the JetStream XC device followed by adjunctive balloon angioplasty in all patients. | Device: JetStream XC with balloon angioplasty<br>* JetStream XC to treat femoropopliteal in-stent restenosis followed by adjunctive balloon angioplasty (same arm). The control arm in this study is historic.<br>* Other names: JetStream Navitus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Target Lesion Revascularization (TLR) | TLR is defined as retreatment of the index lesion (extended 1 cm proximal and distal to the lesion) at 6 months. For the primary endpoint, intra-procedural bail out stenting of the index lesion is considered meeting a TLR endpoint. (ITT analysis) | 6 months | 
| Major Adverse Events (MAE) | unplanned major amputation, all cause mortality, and Bailout Stenting consider Target Lesion Revascularization (TLR). | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device Outcome | Categorized by < 50% residual stenosis following JS atherectomy alone and without additional adjunctive PTA or bail out procedures as determined by the Angiographic Core Laboratory. | Intraprocedural | 
| Procedural Success | Defined as ≤30% residual diameter stenosis following JS + PTA without provisional or bailout procedures | Intraprocedural | 
| Target Lesion Revascularization (TLR) With no Bailout Stent Included | TLR is defined as retreatment of the index lesion (extended 1 cm proximal and distal to the lesion) at 6 months. Intra-procedural bail out stenting of the index lesion is NOT considered meeting a TLR endpoint. (ITT analysis) | 6 months | 
| Target Lesion Revascularization (TLR) | TLR is defined as retreatment of the index lesion (extended 1 cm proximal and distal to the lesion) at 1 year ITT (bail out stent in the Lab is not considered as TLR) | 1 year | 
| Clinical Patency | Defined as PSVR ≤ 2.5 at the treated site or < 50% stenosis by angiography as determined by the Angiographic Core Laboratory in the absence of TLR, amputation, and/or surgical bypass (the evaluation of patency is extended to one cm proximal and one cm distal to the target lesion) | 6 months | 
| Clinical Patency | Defined as PSVR ≤ 2.5 at the treated site or < 50% stenosis by angiography as determined by the Angiographic Core Laboratory in the absence of TLR, amputation, and/or surgical bypass (the evaluation of patency is extended to one cm proximal and one cm distal to the target lesion) | 1 year | 
| Change in Walking Impairment Questionnaire Score | Defined as the change in mean Walking Impairment Questionnaire (WIQ) score at 6 months minus baseline. WIQ score range is 0 to 56. A higher score means a better outcome. WIQ is reported as a change between baseline and 6 months in the score (WIQ score at 6 months minus WIQ score at baseline) | Baseline and 6 months | 
| Number of Participants With Rutherford Clinical Category Improvement | Defined as the change in clinical status indicated by the number of participants that had one improvement of their Rutherford Becker category by at least 1 category at 6 months. The Rutherford category is done on a scale of 0 (no symptoms) to 6 (gangrene/ulceration). A change downward from one category to another is considered an improvement. | 6 months | 
| Change in Ankle-Brachial Index | Defined as the mean ankle-brachial index (ABI) at 6 months minus mean ABI at baseline in subjects with compressible arteries and baseline ABI < 0.9 (0 to 1.2 is the scale ranging from severe disease to normal respectively; higher is better). | 6 months | 
| Change in Walking Impairment Questionnaire at 1 Year | Defined as the change in mean Walking Impairment Questionnaire (Score 0 to 56. A higher score means a better outcome) from Baseline minus at one Year. 29.2-48.8 is the confidence interval minimum and maximum values. | 1 Year | 
| Rutherford Clinical Category | Defined as the change in clinical status indicated by the change in Rutherford Becker Class at 1 Year compared to baseline by at least one category that is attributable to the treated limb (in cases of bilateral disease). Categories are 0 which is asymptomatic to 6 which is gangrene. (Rutherford Becker Category:0=Asymptomatic, 1 = Mild Claudication, 2=moderated claudication, 3= severe claudication, 4= resting pain, 5= ulcers, 6= ulcers with gangrene. | 1 Year | 
| Ankle Brachial Index | Defined as the change in mean ankle-brachial index (ABI) at 1 Year minus mean ABI at baseline in subjects with compressible arteries and baseline ABI < 0.9. Units on a Scale: 0 to 1.2 (worse to normal respectively) | 1 Year | 
| Clinically Driven Target Lesion Revascularization | Clinically-driven TLR (CD-TLR) at 6 months was defined as any reintervention or bypass graft surgery involving a target lesion with a ≥70% diameter stenosis by angiography or PSVR >3.5 and at least 2 of the following associated events: ≥1-level worsening of the Rutherford category, worsening WIQ score by ≥20 points, or an ABI drop >0.15 between baseline and follow-up. | 6 months | 
| Clinically Driven Target Lesion Revascularization | Clinically-driven TLR (CD-TLR) was defined as any reintervention or bypass graft surgery involving a target lesion with a ≥70% diameter stenosis by angiography or PSVR >3.5 and at least 2 of the following associated events: ≥1-level worsening of the Rutherford category, worsening WIQ score by ≥20 points, or an ABI drop >0.15 between baseline and follow-up. | 12 months |