Complete Lesion Assessment With ffR and IVUS TechnologY

Study Overview
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Brief Summary
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CLARITY I is a pilot study to identify the clinically appropriate endpoint(s) of a larger, statistically powered pivotal trial for treatment of patients with Critical Limb Ischemia (CLI).

Detailed Description
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This prospective, randomized, multi-center, post-market study of approximately 50 subjects randomized 1:1 to Orbital Atherectomy (OA) performed with Cardiovascular Systems, Inc.'s Orbital Atherectomy System (OAS) followed by adjunctive balloon angioplasty (BA) vs. BA alone for treatment of tibial vessel disease, defined as ≥ 50 % stenosis of the anterior tibial (AT), posterior tibial (PT), tibial peroneal trunk (TPT), or peroneal (PR) arteries by angiography. All subjects will have a corresponding wound being fed by the target vessel which will be assessed during the study. Subjects will be followed to one year.

Official Title
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Complete Lesion Assessment With ffR and IVUS TechnologY (CLARITY I)

Conditions
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Peripheral Artery Disease, Critical Limb Ischemia

Intervention / Treatment
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* Device: Orbital Atherectomy System
* Device: Balloon Angioplasty


Participation Criteria
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Eligibility Criteria
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General Inclusion Criteria: Subject's age ≥ 18 years. Subject is an acceptable candidate for percutaneous intervention with the Sponsor's OAS and BA in accordance with their labeled indications and instructions for use. Subject is willing and able to sign an approved informed consent form (ICF). Subject is willing and able to attend follow-up and wound care visits. General Exclusion Criteria: Subject is pregnant or planning to become pregnant within the study period. Subject is currently participating in an investigational drug or other device study that can clinically interfere with the endpoints of this trial. Subject has a known sensitivity to contrast media and the sensitivity cannot be adequately pre-medicated. Uncontrolled allergy to nitinol, stainless steel, or other stent materials. Subject has known allergy to atherectomy lubricant components such as soybean oil, egg yolk phospholipids, glycerin or sodium hydroxide. Subject has a history of bleeding diathesis or coagulopathy or will refuse blood transfusions. Subject has been diagnosed with chronic renal failure or has a creatinine level > 2.5, unless on dialysis, prior to the index treatment. Subject has evidence of intracranial or gastrointestinal bleeding within 90 days. Subject has a history of trauma, fracture, major surgery (includes major amputation), or biopsy of a parenchymal organ within past 14 days, or patient has not healed from a previous medical intervention occurring more than 14 days. Subject has a history of stroke or myocardial infarction (MI) within 90 days prior to enrollment in the study. Subject has a planned major surgery (includes major amputation) scheduled within 60 days after treatment of the index limb. Subject has a planned interventional treatment to address stenosis of the contralateral limb scheduled within 60 days after the index treatment. Subject has a planned interventional treatment to address inflow stenosis of the ipsilateral limb scheduled within 60 days after the index treatment. Inflow or bilateral PAD requiring treatment prior to enrollment was not successfully treated, defined as > 50% residual stenosis and/or occurrence of procedural angiographic complications, excluding dissection types A and B. Subject has previously had their other limb treated as part of the study. Angiographic Inclusion Criteria: Target lesion(s) located in the anterior tibial (AT), posterior tibial (PT), tibial peroneal trunk (TPT) or peroneal (PR) arteries. Target lesion has ≥ 50 % stenosis by angiography. Subject has a corresponding wound being fed by the target vessel. Angiographic Exclusion Criteria: Target limb does not have any visual flow to the foot confirmed via distal selective angiography. Thrombus is present or suspected in the target treatment vessel. Target lesion is within a bypass graft or near a previously placed stent. The guide wire cannot be passed across the target lesion. Anterograde access of the lesion is not possible. Subject has angiographic evidence of significant dissection at or near the treatment site. Interventional treatment is intended for in-stent restenosis at the peripheral vascular site. Subject's wound(s) involve multiple angiosomes.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orbital Atherectomy System<br>Orbital Atherectomy (OA) is performed prior to adjunctive Balloon Angioplasty (BA) | Device: Orbital Atherectomy System<br>* Orbital atherectomy (OA) is performed prior to adjunctive balloon angioplasty (BA)<br>Device: Balloon Angioplasty<br>* Type of balloon selected is driven by preference of the operator.<br>|
| Active Comparator: Balloon Angioplasty<br>Balloon Angioplasty (BA) alone | Device: Balloon Angioplasty<br>* Type of balloon selected is driven by preference of the operator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Calcium Removal Out of Lumen Gain as Assessed by IVUS | The post-treatment percentage of calcium removal out of lumen gain at the maximum calcium ablation site. A positive value equates to reduction in calcium out of the lumen gain. | Post-balloon angioplasty | 
| Change in Minimum Lumen Area Percent Stenosis as Assessed by IVUS | The pre- (Pre-Tx) and post-treatment (Post-Tx) minimum lumen area percent stenosis. A positive value equates to a decrease in lumen area percent stenosis. | Pre-intervention, and post-balloon angioplasty | 
| Change in Plaque Area as Assessed by IVUS | The pre- (Pre-Tx) and post-treatment (Post-Tx) plaque area. A positive value equates to a decrease in plaque area. | Pre-intervention, and post-balloon angioplasty | 
| Change in Dense Calcium Area as Assessed by IVUS | The pre- (Pre-Tx) and post-treatment (Post-Tx) dense calcium area. A positive value equates to a decrease in dense calcium area. | Pre-intervention, and post-balloon angioplasty | 
| Change in Necrotic Core Area as Assessed by IVUS | The pre- (Pre-Tx) and post-treatment (Post-Tx) necrotic core area. A positive value equates to a decrease necrotic core area. | Pre-intervention, and post-balloon angioplasty | 
| Change in Fibrous Plaque Area as Assessed by IVUS | The pre- (Pre-Tx) and post-treatment (Post-Tx) fibrous plaque area. A positive value equates to a decrease in fibrous plaque area. | Pre-intervention, and post-balloon angioplasty | 
| Change in Fibrofatty Plaque Area as Assessed by IVUS | The pre- (Pre-Tx) and post-treatment (Post-Tx) fibrofatty plaque area. A positive value equates to a decrease in fibrofatty plaque area. | Pre-intervention, and post-balloon angioplasty | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractional Flow Reserve | Fractional flow reserve (FFR) will be measured to assess hemodynamic function following each device procedure. During FFR, adenosine will be given through the femoral artery sheath or access catheter in two doses: 600 mcg and 1200 mcg. A higher FFR is presumed to correlate to better flow which may improve wound healing. | Post-orbital atherectomy (OA arm only) and post-balloon angioplasty (both arms) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peripheral Artery Disease, Critical Limb Ischemia, Orbital Atherectomy, Balloon Angioplasty, Intravascular Ultrasound (IVUS), Fractional Flow Reserve (FFR)