IN.PACT BTK Randomized Study to Assess Safety and Efficacy of IN.PACT 014 vs. PTA

Study Overview
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Brief Summary
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To assess the safety and efficacy of the paclitaxel drug-eluting balloon IN.PACT 014 versus conventional percutaneous transluminal angioplasty (PTA) for the treatment of patients with chronic total occlusions in the infrapopliteal arteries.

Official Title
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Randomized Study of IN.PACT 014 Paclitaxel-Coated Percutaneous Transluminal Angioplasty Balloon Catheter vs. Standard Percutaneous Transluminal Angioplasty for the Treatment of Chronic Total Occlusions in the Infrapopliteal Arteries

Conditions
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Critical Limb Ischemia, Peripheral Arterial Disease

Intervention / Treatment
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* Device: DCB
* Device: PTA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years. Subject has been informed of the nature of the study, agrees to participate and has signed an EC approved consent form. Female subjects of childbearing potential have a negative pregnancy test ≤7 days before the procedure and are willing to use a reliable method of birth control for the duration of study participation. Subject has documented chronic Critical Limb Ischemia (CLI) in the target limb prior to the study procedure with Rutherford Clinical Category 4 or 5. Subjects with documented infection grade 0-2 and ischemia grade 2-3 according to WIfi classification. Life expectancy >1 year in the Investigator's opinion. Reference Vessel Diameter (RVD) 2 - 4 mm, and confirmed by DUS assessment. Total occlusions with total lesion length ≥ 40 mm. Lesion must be located in the infrapopliteal arteries and above the ankle joint. Multiple lesions can be treated if located in separate vessels. Presence of documented run-off to the foot. Inflow free from flow-limiting lesion confirmed by angiography. Successful pre-dilatation of the (entire) target lesion. Exclusion Criteria: Subject unwilling or unlikely to comply to the appropriate follow-up times for the duration of the study. Planned index limb amputation above the metatarsal level, or any other planned major surgery within 30 days pre or post-procedure. Lesion and/or occlusions located or extending in the popliteal artery or below the ankle joint space. Significant inflow lesion or occlusion in the ipsilateral iliac, SFA and popliteal arteries left untreated. Failure to obtain ≤ 30% residual stenosis in pre-existing, hemodynamically significant inflow lesions in the ipsilateral iliac, SFA and popliteal artery. Prior stent(s) or bypass surgery within the target vessel(s) (including stents placed within target vessels during the index procedure prior to randomization. Previous DCB procedure in the target vessel within 6 months prior to index procedure. Aneurysm in the target vessel. Angiographic evidence of thrombus within target limb. Pre-dilatation resulted in major (≥ Grade D) flow-limiting dissection or residual stenosis > 30%. Use of alternative therapy e.g. atherectomy, cutting balloon, laser, radiation therapy, stents as part of target vessel treatment. Recent MI or stroke < 30 days prior to the index procedure. Heart failure with Ejection Fraction < 30%. Known or suspected active infection at the time of the index procedure, excluding an infection of a lower extremity wound on the target limb. Subjects with infection grade 3 and ischemia grade 0 and 1 according to the Wifi classification. Subjects with neutrotrophic ulcers, heel pressure ulcers or calcaneal ulcers with a risk of major amputation. Subjects with documented active osteomyelitis, excluding the phalanges, that is beyond cortical involvement of the bone per clinical judgement. Impaired renal function (GFR <20 mL/min) and patients on dialysis. Subject with vasculitis, systemic Lupus Erythematosus or Polymyalgia Rheumatica on active treatment. Patient receiving systemic corticosteroid therapy. Known allergies or sensitivities to heparin, aspirin (ASA), other anticoagulant/anti-platelet therapies which could not be substituted, and/or paclitaxel or an allergy to contrast media that cannot be adequately pre-treated prior to the index procedure. The patient is currently enrolled in another investigational device or drug trial that is interfering with the endpoints of this study. Female subjects who are breastfeeding at the time of enrollment.

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: drug-eluting balloon IN.PACT 014<br>product is indicated for PTA in patients with obstructive disease of peripheral arteries with paclitaxel drug - elution. | Device: DCB<br>* Drug Coated Balloon<br>|
| Active Comparator: Standard angioplasty balloon<br>standard PTA balloon | Device: PTA<br>* Percutaneous Transluminal Angioplasty<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Late lumen loss (LLL) at 9 months | Late lumen loss (LLL) at 9 months | 9 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Safety Endpoint | A composite of freedom from device- and procedure-related mortality within 30 days, freedom from major target limb amputation and freedom from clinically-driven target lesion revascularization (CD-TLR) within 9 months post-index procedure. | 30 days and 9 Months | 
| Major Adverse Event (MAE) rate | defined as a composite of all-cause mortality, target limb major amputation and clinically-driven target lesion revascularization (CD-TLR) | through 3, 6, 9, 12, 24, 36, 48 and 60 months | 
| Status of wound healing | completely healed - improvement - unchanged - worsened | at 30 days, 3, 6, 9, 12, 24 and 36 months | 
| Rate of thrombosis at the target lesion | Rate of thrombosis at the target lesion | through 30 days, 3, 6, 9, 12, 24, 36, 48 and 60 months | 
| Device success | is defined as successful drug delivery, balloon inflation, deflation and retrieval of the intact study device without burst below the rated burst pressure (RBP). | at the time of procedure | 
| Clinical success | is defined as residual stenosis of ≤ 30% without procedural complications (death, major target limb amputation, thrombosis of the target lesion, or target vessel revascularization (TVR)) | up to discharge visit | 
| Functional flow assessment | is defined as absence of target lesion occlusion (no flow) assessed by duplex ultrasound | at 3, 6, 9, 12, 24 and 36 months | 
| Death of any cause and cardiovascular-related deaths | Death of any cause and cardiovascular-related deaths | through 3, 6, 9, 12, 24, 36, 48 and 60 months | 
| Major Target Limb Amputation rate | Major Target Limb Amputation rate | through 30 days, 3, 6, 9, 12, 24, 36, 48 and 60 months | 
| Mechanically-driven Target Lesion Revascularization (TLR) rate | Mechanically-driven Target Lesion Revascularization (TLR) rate | through 37 days | 
| Target Lesion Revascularization (TLR) rate | Target Lesion Revascularization (TLR) rate | through 3, 6, 9, 12, 24, 36, 48 and 60 months | 
| Clinically-driven Target Lesion Revascularization (CD-TLR) rate | Clinically-driven Target Lesion Revascularization (CD-TLR) rate | through 3, 6, 9, 12, 24, 36, 48 and 60 months | 
| Target Vessel Revascularization (TVR) rate | Target Vessel Revascularization (TVR) rate | through 3, 6, 9, 12, 24, 36, 48 and 60 months | 
| Clinically-driven Target Vessel Revascularization (CD-TVR) rate | Clinically-driven Target Vessel Revascularization (CD-TVR) rate | through 3, 6, 9, 12, 24, 36, 48 and 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug-eluting angioplasty balloon, Drug coated angioplasty balloon, Experimental, percutaneous transluminal angioplasty (PTA)