The HERCULES Trial - A Safety and Effectiveness Study of the Herculink Elite Renal Stent to Treat Renal Artery Stenosis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the Herculink Elite Renal Stent System is safe and effective in the treatment of renal artery stenosis in patients with less than optimal angioplasty results and uncontrolled hypertension. CAUTION: The Herculink Elite Renal Stent System Is An Investigational Device. Limited by Federal (U.S.) Law to Investigational Use Only.

Detailed Description
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To evaluate the safety and effectiveness of the RX Herculink Elite Renal Stent System in the treatment of suboptimal post-procedural percutaneous transluminal angioplasty (PTA) of atherosclerotic de novo or restenotic renal artery stenosis in patients with uncontrolled hypertension. CAUTION: The Herculink Elite Renal Stent System Is An Investigational Device. Limited by Federal (U.S.) Law to Investigational Use Only.

Official Title
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A Clinical Trial to Assess the Safety and Efficacy of the RX Herculink(R) Elite(TM) Renal Stent System for the Treatment of Suboptimal Post-procedural Percutaneous Transluminal Angioplasty (PTA) in de Novo or Restenotic Renal Artery Stenoses in Patients With Uncontrolled Hypertension.

Conditions
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Hypertension, Renal, Renal Artery Obstruction

Intervention / Treatment
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* Device: Herculink Elite Renal Stent System


Participation Criteria
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Eligibility Criteria
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General Clinical Inclusion Criteria: Subject is ≥18 years of age. Subject and subject's physician agree to have the subject return for all required contact following study enrollment. Subject has been informed of the nature of the study, and has provided written informed consent, approved by the appropriate Institutional Review Board (IRB) of the respective clinical site. Subject is a candidate for renal artery stenting. Subject has uncontrolled systolic hypertension (systolic Blood Pressure[SBP] ≥140 mmHg), or uncontrolled diastolic hypertension (diastolic BP [DBP] ≥90 mmHg), or a combination of both in the presence of at least two (2) or more antihypertensive medications. Subject has a baseline serum Creatinine of <2.5mg/dl Angiographic Inclusion Criteria Subject has either unilateral or bilateral de novo or restenotic after Percutaneous Transluminal Angioplasty (PTA) (in-stent restenosis excluded) atherosclerotic lesion(s). If bilateral lesions are to be treated, the most severe lesion must be successfully treated without complications before progressing to treat the second lesion. Treatment of bilateral lesions is to occur in the same procedural event. Renal stenosis must be visually estimated to be ≥60% by angiography. Subject has a suboptimal PTA result, defined as one of the following: ≥50% residual stenosis 10 mm Hg mean gradient or 20 mm Hg peak systolic gradient across the target lesion A flow-limiting dissection (NHLBI grade D) or TIMI flow <3 Renal stenosis must be visually estimated to be within 10 mm of the aortic renal border by angiography. Target vessel reference diameter must be visually estimated to be ≥4mm and ≤7mm by angiography Target lesion length must be visually estimated to be ≤15mm (including dissection) by angiography. Expected ability to deliver the stent to the lesion (absence of excessive tortuosity or calcification). Expected ability to fully expand the stent. Clinical Exclusion Criteria Subject has known hypersensitivity or contraindication to cobalt chromium or standard intraprocedure anticoagulant(s); subject has sensitivity to contrast which cannot be adequately pre-treated with medication. Subject has known allergy or contraindication to clopidogrel (Plavix) or aspirin. Subject has known bleeding disorder or hypercoagulable disorder, or will refuse blood transfusions. Subject has suffered a gastrointestinal (GI) bleed within 30 days before the index procedure that would interfere with antiplatelet therapy. Subject has renal insufficiency defined as serum Creatinine >2.5 mg/dl. Subject has any immunosuppressive disorder, access site infection, or acute systemic infection due to any cause. Subject has other medical illnesses (e.g., cancer, end-stage congestive heart failure) that may cause the subject to be non-compliant with protocol requirements, confound the data interpretation, or is associated with a life expectancy of less than three years. Subject has any medical illnesses that would make them unlikely to respond to treatment (e.g., sickle cell nephropathy/sickle cell disease, scleroderma, arteriolar nephrosclerosis, hemolytic-uremic syndrome and vasculitis). Subject has had a Q-wave MI within 30 days before index procedure. Subject has had a stroke or TIA within 30 days before index procedure. Subject has a history of congestive heart failure and has a previously documented LVEF ≤25%. Subject is normotensive or has adequate control of hypertension (SBP <140 mmHg and DBP <90 mm Hg) utilizing diet control and/or medication regimen involving only one antihypertensive medication. Subject has acute thrombophlebitis or deep vein thrombosis. Subject is actively participating in another drug or device trial and has not completed the required protocol follow-up period. Subject may be enrolled only once in this study (Protocol # 05-102) and may not participate in any other clinical trial during the follow-up period. Subject is unable to understand and cooperate with study procedures or provide informed consent. Subject is unable to return for follow-up visits (distance, etc). Subject is pregnant. Subject has undergone vascular surgery (CABG, AAA repair, AF bypass) and has not fully recovered from the effects of surgery (<3 months). Subject has planned staged treatment of bilateral renal artery stenosis. Subject has had prior surgical intervention to the target artery, or has undergone previous stent placement in the target lesion. Target lesion is located in a transplanted kidney. Kidney to be treated is <8 cm as determined by duplex ultrasound report, CTA report, or MRA report within 180 days before procedure. If kidney size is documented by more than one method, e.g. CTA and ultrasound, and one of the methods is duplex ultrasound, the kidney size as documented by duplex ultrasound shall be used to determine study eligibility. Subject has planned additional ancillary procedure(s) during renal stenting procedure. Angiographic Exclusion Criteria Subject has a lesion segment, including dissection, >15 mm in length. Requirement for >1 stent to treat full length of lesion and dissection. Target lesion has a total (100%) occlusion. Evidence of thrombus or mobile filling defect in the target lesion or vessel. Subject has co-existing aneurysmal or occlusive disease of the abdominal aorta requiring surgical reconstruction during the follow-up period. Target lesion is non-atherosclerotic (fibromuscular dysplasia). Subject artery has patent bifurcation within 10 mm of ostium that might be covered by placement of a stent. The target lesion is within the artery of a solitary functioning kidney or, the subject has a contralateral totally occluded renal artery. For planned treatment of bilateral lesions: the more critical lesion, i.e. lesion with the greater stenosis (which should be treated first), is either treated unsuccessfully or requires a bailout procedure. (NOTE: Less critical lesion is excluded at this point.) Subject has any condition that precludes proper angiographic assessment or makes percutaneous arterial access unsafe. The target lesion is densely calcified and will not yield during balloon dilation. Subject has had recent change in renal function after unrelated catheter or surgical procedure with the clinical stigmata of atheroemboli syndrome (i.e., livedo reticularis: non-occlusive mesenteric ischemia; digital gangrene; progressive renal insufficiency without other identifiable etiology). Subject has an accessory renal artery that has >50% stenosis. Accessory renal arteries may not be stented as part of this study.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RX Herculink Elite<br>To evaluate the safety and effectiveness of the RX Herculink Elite Renal Stent System in the treatment of suboptimal post-procedural percutaneous transluminal angioplasty (PTA) of atherosclerotic de novo or restenotic renal artery stenosis in patients with uncontrolled hypertension. | Device: Herculink Elite Renal Stent System<br>* This is a prospective, non-randomized, single arm, multi-center study to evaluate the safety and effectiveness of the RX Herculink Elite Renal Stent System in patients with sub-optimal renal PTA results in de novo or restenotic renal artery lesions. Patients who satisfy the inclusion/exclusion criteria will be enrolled at sites in the United States. Patients will have follow up visits for evaluation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Binary Restenosis Rate | Determined by duplex ultrasound or angiogram. Reported as the percentage of participants with occurance of binary restenosis. | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death for Any Reason |  | 30 days | 
| Ipsilateral Nephrectomy | Ipsilateral: Situated on or affecting the same side as treated. Nephrectomy: Removal of the affected kidney | 30 days | 
| Embolic Events Resulting in Kidney Damage | Percentage of participants with an embolic event resulting in kidney damage. | 30 days | 
| Event Free Rate of Clinically Indicated Target Lesion Revascularization (TLR) | Event Free percentage: Defined as percentage of participants free from this event. | 9 months | 
| 9 Month Blood Pressure (Systolic) | As compared to baseline (pre-procedure). Blood pressure measurements at 9 months. | Baseline (Pre-Procedure) and 9 months | 
| 9 Month Blood Pressure (Diastolic) | As compared to baseline. See Population description. | 9 months and baseline | 
| Acute Device Success | Acute device success is defined as, on a per device basis, the achievement of successful delivery of the assigned device(s)as intended to the designated location. | From beginning of index procedure to end of index proceedure. | 
| Acute Procedure Success | Attainment of a final result of < 30% residual stenosis, as determined by the Angiographic Core Lab. | From beginning of index proceedure to end of index proceedure. | 
| Acute Clinical Success | Procedure success without Major Adverse Events (MAE)or access site event requiring surgical or percutaneous intervention prior to hospital discharge. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. | From beginning of index proceedure to end of index proceedure. | 
| Primary Patency | Defined as <60% stenosis without prior re-intervention, as determined by duplex ultrasound or angiogram. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. | 9 months | 
| Secondary Patency Rate of <60% Stenosis of the Target Lesion | As determined by duplex ultrasound or angiography regardless of PTA, stenting, or bypass since index procedure. Rate reported as a percentage of participants with this condition. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. | 9 months | 
| 9 Month Anti-hypertensive Medication In-take, 1 Medication | Number of Anti-Hypertensive Medications taken-baseline compared to follow up, Per Subject Analysis (Intent-to-Treat Population), reported as the percentage of participants using the number of medications indicated. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. | 9 months | 
| 9 Month Anti-hypertensive Medication In-take, 2 Medications | Number of Anti-Hypertensive Medications taken-baseline compared to follow up, Per Subject Analysis (Intent-to-Treat Population)), reported as the percentage of participants using the number of medications indicated. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. | 9 months | 
| 9 Month Anti-hypertensive Medication In-take, 3 Medications | Number of Anti-Hypertensive Medications taken-baseline compared to follow up, Per Subject Analysis (Intent-to-Treat Population)), reported as the percentage of participants using the number of medications indicated. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. | 9 months | 
| 9 mo in Anti-hypertensive Medication In-take, ≥ 4 Medications | Number of Anti-Hypertensive Medications taken at follow up compared to baseline, Per Subject Analysis (Intent-to-Treat Population)), reported as the percentage of participants using the number of medications indicated. The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. | 9 months | 
| Renal Function (Measured by sCr) | sCR= Serum Creatinine, per subject analysis. ITT. Renal function (measured by sCr) @ baseline: 1.2mg/dL (1.2, 1.3). The analysis population at clinical follow-up visits may have changed due to early termination from the study by the patient or physician. | 9 months |