Effectiveness of Adventitial Dexamethasone in Peripheral Artery Disease

Study Overview
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Brief Summary
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To assess the safety and effectiveness of adventitial deposition of the Study Drug in reducing inflammation and restenosis in patients with clinical evidence of claudication or critical limb ischemia and an angiographically significant lesion in the superficial femoral and/or popliteal arteries. Study Drug and Dose: Dexamethasone Sodium Phosphate Injection, USP, 4 mg/ml, with dilute contrast (17%) administered to the adventitia in a dose of 1.6 mg per cm of desired vessel treatment length.

Detailed Description
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This trial will examine the ability for adventitial dexamethasone to safely delay restenosis in patients at least 18 years of age, who have peripheral atherosclerotic lesions involving the superficial femoral and/or popliteal arteries. These patients have no current therapeutic alternatives beyond the procedure used to open, or revascularize, their superficial femoral and/or popliteal arteries. Metal stents have the potential to fracture when implanted in this artery segment due to continual flexion and bending of the knee. It is desirable to improve the patency of this artery after percutaneous transluminal angioplasty (PTA) and/or atherectomy-based revascularization.

Official Title
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Delivery of Dexamethasone to the Adventitia to eNhance Clinical Efficacy After Femoropopliteal Revascularization

Conditions
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Peripheral Arterial Diseases

Intervention / Treatment
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* Drug: Dexamethasone Sodium Phosphate Injection, USP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Screening Criteria Male or non-pregnant female ≥18 years of age Rutherford Clinical Category 2-4 Clinical diagnosis of PAD requiring revascularization, secondary to atherosclerosis affecting a lower limb Patient is willing to provide informed consent and comply with the required follow up visits, testing schedule, and medication regimen Procedural Criteria De novo or nonstented restenotic lesions >90 days from prior angioplasty and/or atherectomy, at least 3 cm from any previously placed stent or vascular surgery site >70% diameter stenosis up to 15 cm in total length (with no greater than 3 cm length of contiguous intervening normal artery) in the superficial femoral and/or popliteal artery (between the profunda and tibioperoneal trunk) Reference vessel diameter ≥3mm and ≤ 8mm Successful wire crossing of lesion A patent artery proximal to the index lesion free from significant stenosis (significant stenosis is defined as >50% in iliac or >30% stenosis in common femoral artery) as confirmed by angiography (treatment of target lesion after successful treatment of iliac or common femoral artery lesions is acceptable) Exclusion Criteria: Screening Criteria Pregnant, nursing or planning on becoming pregnant in < 2 years Life expectancy of <2 years Known active malignancy History of solid organ transplantation Patient actively participating in another investigational device or drug study History of hemorrhagic stroke within 3 months Previous or planned surgical or interventional procedure within 30 days of index procedure Chronic renal insufficiency with eGFR <29 Prior bypass surgery, stenting of the target lesion Inability to take required study medications Contra-indication or known hypersensitivity to dexamethasone sodium phosphate, contrast media, or Physician prescribed antiplatelet regimen as indicated Systemic fungal infection Anticipated use of IIb/IIIa inhibitor prior to index lesion treatment Acute or sub-acute thrombus, acute vessel occlusion or sudden symptom onset Acute limb ischemia Prior participation of the index limb in the current study (contralateral treatment is allowed) Inability to ambulate (e.g. from prior ipsilateral or contralateral amputation) Patient is receiving steroids already, however locally acting inhaled steroids for asthma treatment do not exclude patients from the trial Procedural Criteria Lesions extending into the trifurcation or above the profunda Heavy eccentric or moderate circumferential calcification at index lesion, which in the judgment of the investigator would prevent penetration of the Micro-Infusion Catheter needle through the vessel wall Lesion length is >15 cm as measured from proximal normal vessel to distal normal vessel, or there is no normal proximal arterial segment in which duplex ultrasound velocity ratios can be measured Inadequate distal outflow defined as absence of at least one patent tibial artery (no lesion >50% stenosis) with flow into the foot Use of adjunctive therapies other than angioplasty, atherectomy (mechanical or laser) or bare metal stenting (i.e. scoring/cutting balloon, drug-eluting stent, drug-coated balloon, cryoplasty, etc.)

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: Adventitial Dexamethasone<br>In patients receiving either angioplasty or atherectomy-based revascularization (pre-stratified to each by 50% of the total study), dexamethasone will be delivered to the adventitia following revascularization. | Drug: Dexamethasone Sodium Phosphate Injection, USP<br>* Adventitial infusion of dexamethasone after angioplasty or atherectomy-based revascularization of the superficial femoral or popliteal artery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MALE-POD | Acute safety safety outcomes will be determined by evaluating the type, frequency, severity, and relatedness of Major Adverse Limb Events or Peri-Operative Death (MALE+POD) within 30 days from the procedure for all subjects. | 30 days | 
| Duplex ultrasound index lesion binary restenosis | Binary restenosis will be judged by core laboratory interpretation with peak systolic velocity ratio (PSVR) greater than 2.4. | 6 months | 
| Duplex ultrasound index lesion binary restenosis | Binary restenosis will be judged by core laboratory interpretation with peak systolic velocity ratio (PSVR) greater than 2.4. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long term safety | Long term safety outcomes that occur after 30 days through 6 months post-procedure will be determined by evaluating adverse events. | 30 days to 6 months | 
| Duplex ultrasound index lesion flow limiting restenosis | Flow limiting restenosis will be judged by core laboratory as PSVR>4.0. | 6 and 12 months | 
| Change in inflammatory biomarkers | Change in inflammatory biomarkers will be measured with a panel of biomarkers in 1/3 of patients. | Baseline and 24 hours | 
| Vascular patency | Target lesion revascularization (TLR) rate, target extremity revascularization (TER) rate, limb salvage rate and primary patency (PSVR≤2.4 and no TLR) at 6, 12, 18 and 24 months. Note: provisional stenting performed during the index procedure shall not be considered to be TLR, TER or loss of primary patency. | 6, 12, 18 and 24 months | 
| Clinical outcome measures | Modified Walking Impairment Questionnaire, Ankle-Brachial Index, Rutherford Score. | 1, 6, 12, 18 and 24 months | 
| Infusion Technical Success | Distribution grade around infusion sites. | Intraprocedural | 
| Procedural Success | Establishment of antegrade flow with residual stenosis of <30% by angiogram. | Intraprocedural | 
| Healthcare Economics | Number of return visits and hospitalizations, time from index procedure to required revascularization and number of index-lesion-related readmissions within 30 days will be measured. | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adventitia, Peripheral Artery Disease, Restenosis, Inflammation, Anti-Inflammatory, Dexamethasone