RENABLATE Feasibility Study CS156 (EC12-02) Study of Catheter Based Renal Denervation to Treat Resistant Hypertension

Study Overview
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Brief Summary
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The RENABLATE feasibility study is a prospective, multi-center, non-randomized feasibility study to evaluate the safety and effectiveness of the investigational multi-electrode ablation catheter and integrated ablation system to treat resistant hypertension.

Detailed Description
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The RENABLATE feasibility study CS156 (EC12-02) is a prospective, multi-center, non-randomized feasibility study to evaluate the safety and effectiveness of renal artery sympathetic denervation using the investigational Celsius® ThermoCool® Renal Denervation (RD) Multi-electrode Ablation Catheter and integrated ablation system to treat resistant hypertension.

Official Title
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A Prospective, Multi-Center, Non-Randomized Feasibility Study of Catheter-Based Renal Denervation to Treat Resistant Hypertension (RENABLATE- EC12-02)

Conditions
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Hypertension, Renal

Intervention / Treatment
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* Device: Celsius® ThermoCool® RD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is > 18 and < 85 years old. Individual has a systolic blood pressure ≥ 160 mmHg (≥ 150 mmHg for type 2 diabetics) based on an average of 3 office blood pressure readings. Individual is adhering to a stable drug regimen of at least 3 different classes of anti-hypertensive medications, including a diuretic (with no changes for a minimum of 2 weeks prior to enrollment) at optimal dose and is expected to be maintained for at least 6 months. Individual agrees to have all study procedures performed, and is competent and willing to provide written, informed consent to participate in this study. Exclusion Criteria: Subjects with known/diagnosed secondary hypertension. Subject has 'White Coat' hypertension defined as 24 hour daytime systolic blood pressure <135 mm Hg as evaluated at Baseline visit. Subject has aorto-ilio-femoral artery anatomy not suitable for treatment with the investigational Celsius® ThermoCool® RD Multi-electrode Ablation Catheter. Subject has main renal arteries that are < 20 mm in length or < 4 mm in diameter. Subject has multiple main renal arteries in either kidney. Subject has a history of prior renal artery intervention including balloon angioplasty, stenting or surgery. Subject had a previous kidney transplant or is a planned recipient of a transplant kidney or is on dialysis. Subject has a past history of unilateral kidney removal or has a solitary functional kidney for any other reason. Subject has an estimated glomerular filtration rate (eGFR) of < 45mL/min/1.73m2, using the MDRD formula. Subject has type 1 diabetes mellitus. Subject has history of Myocardial Infarction, unstable angina pectoris, or a cerebrovascular accident in the 6 months period prior to enrolment, or documented widespread atherosclerosis, intravascular thrombosis or unstable plaques. Subject had a significant surgery or cardiovascular intervention in the 6 months period preceding enrollment or is planned to have such a surgery or cardiac intervention in the 6 months period post enrollment. Subject has hemodynamically significant valvular heart disease for which reduction of blood pressure would be considered hazardous. Subject is taking systemic steroids or chronic daily NSAIDs. Subject has a known allergy to Aspirin and/or other procedural drugs or contrast agents which in the investigator's opinion excludes him/her from the study. Subject has a serious medical condition, which in the opinion of the investigator, may adversely affect the safety and/or effectiveness of the participant or the study (e.g., subjects with active systemic infection, subjects with clinically significant peripheral vascular disease, abdominal aortic aneurysm, bleeding disorders such as thrombocytopenia, hemophilia, or significant anemia). Women of childbearing potential with a positive pregnancy test during screening OR women who do not agree to remain on birth control until follow-up at 6 months OR lactating women. Subject has a known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or would be unlikely or unable to comply with study follow-up requirements. Subject is currently enrolled in another investigational drug or device trial.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 84 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: Resistant Hypertension<br>The catheter-based (device: Celsius® ThermoCool® RD) renal denervation will serve to treat resistant hypertension. | Device: Celsius® ThermoCool® RD<br>* The investigational device is designed to transmit radiofrequency (RF) current to the electrodes for ablation purposes, specifically for the treatment of resistant hypertension by renal denervation.<br>* Other names: Multi-electrode Ablation Catheter;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence of Major Cardiovascular and/or Renal Adverse Events Related to the Renal Denervation Procedure That Occurred Within 30 Days Post-procedure. | The major adverse events include Acute myocardial infarction, Death from progressive heart failure, death from aortic or peripheral artery disease, from renal failure and sudden cardiac death, New-onset heart failure, Stroke, Aortic or lower limb, revascularization procedure, Lower limb amputation, Beginning dialysis, Hospital admission for hypertensive emergency unrelated to non-adherence or non-persistence with drugs at each follow up visit, Hospitalization for atrial fibrillation. | 30 days post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects Experienced Any Adverse Cardiovascular and Renal Events Through 12 Months Post-procedure | These adverse events include renal artery stenosis (≥60% diameter reduction confirmed by MRI or renal angiography); periprocedural renal artery dissection or perforation requiring intervention, serious arterial access site related complications requiring intervention or prolonging hospitalization; ≥25% reduction between baseline and 12 months in renal function measured by the estimated Glomerular Filtration Rate (eGFR), as well as composite of major adverse cardiovascular and/or renal events. | 12 months post-procedure | 
| Actual and Change in Office Systolic Blood Pressure and Diastolic Blood Pressure From Baseline to 1 ,3, 6 and 12 Months Post Procedure | This secondary effectiveness endpoint is defined as actual and change in office systolic blood pressure and diastolic blood pressure from baseline to 1 ,3, 6 and 12 months post procedure. Negative values represent reduction from baseline. | From baseline to 1 ,3, 6 and 12 months post procedure | 
| Actual and Change in 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure and Diastolic Blood Pressure From Baseline to 3, 6 and 12 Months Post Procedure | This secondary effectiveness endpoint is defined as change in 24-hour ABPM systolic blood pressure and diastolic blood pressure from baseline to 3, 6 and 12 months post procedure. The blood pressures were measured using the 24-hour Ambulatory Blood Pressure Monitoring system. Reported values are the arithmetic mean of collected blood pressure values over 24 hours. Negative values represent reduction from baseline. | From baseline to 3, 6 and 12 months post procedure | 
| Incidence of Subjects Achieving Target Systolic Blood Pressure at 1, 3, 6, and 12 Month Post-procedure | This endpoint is defined as incidence of subjects achieving target systolic blood pressure at 1, 3, 6, and 12 month post-procedure. Target systolic blood pressure is defined as less than 140 mmHg (and less than 130 mmHg for Type II Diabetics). | At 1, 3, 6, and 12 month post-procedure | 
| Incidence of Subjects Achieving at Least 10 mmHg Systolic Blood Pressure Reduction From Baseline at 1, 3, 6, and 12 Month Post-procedure | This endpoint is defined as Incidence of subjects achieving at least 10 mmHg systolic blood pressure reduction from Baseline at 1, 3, 6, and 12 month post-procedure | At 1, 3, 6, and 12 month post-procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Essential Hypertension, Renal Denervation, Vascular Disease, Renal Catheter Ablation, Primary Hypertension