First-In-Human Study Evaluating a Novel Catheter Device in Subjects With Treatment-Resistant Hypertension

Study Overview
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Brief Summary
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The carotid body is located at the bifurcation of the internal and external carotid arteries. It is a chemoreceptor that plays a role in the sympathetic nervous system and in the development and maintenance of hypertension. Hypertension is a major cardiovascular risk factor and is associated with coronary artery disease, stroke, chronic kidney disease, and heart failure. The objective of this study is to assess the effectiveness and safety of a catheter-based system to ablate the carotid body and reduce blood pressure (BP) in patients with resistant hypertension and to confirm sustainability of the treatment benefits long-term as seen following surgical CB removal.

Official Title
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First-In-Human Study for Ultrasound Based Endovascular Carotid Body Ablation in Subjects With Treatment-Resistant Hypertension: A Safety and Feasibility Study

Conditions
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Hypertension,Essential

Intervention / Treatment
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* Device: Catheter-Based Carotid Body Ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mean office SBP ≥160 mmHg and DBP ≥90 mmHg during screen-in period Mean daytime systolic ABPM ≥135 mmHg during screen-in period Adherent to a stable drug regimen of three (3) or more anti-hypertensive medications of different classes (including one (1) diuretic), with no medication changes expected for at least six (6) months post-procedure No change in anti-hypertensive drug prescription (dose, number of medications, or class of medication) for at least six (6) weeks prior to enrollment Negative pregnancy test for women of child-bearing age Willingness and able to comply with follow-up requirements Signed informed consent Exclusion Criteria: Secondary causes of hypertension Calculated eGFR <30mL/min/1.73m2 History of repeated episodes of hypoglycemic unawareness Morbid obesity, defined as Body Mass Index >40 kg/m2 Severe obstructive sleep apnea (AHI > 35/hr.) Pacemaker and/or implantable defibrillators History of transient ischemic accident or cerebrovascular accident during six (6) months prior to screening History of acute heart failure, congestive heart failure (NYHA class III-IV), myocardial infarction, unstable angina, coronary bypass or coronary angioplasty during six (6) months prior to screening History of ipsilateral carotid endarterectomy treatment or ipsilateral carotid artery stenting

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: Catheter-Based Carotid Body Ablation<br>All subjects undergo catheter-based ablation of the carotid body using the Cibiem Transvenous Ultrasound System (CTUS). | Device: Catheter-Based Carotid Body Ablation<br>* The Cibiem Transvenous Ultrasound System (CTUS) is a catheter based device delivering ultrasound energy to ablate the carotid body. The procedure is done via a percutaneous insertion of the CTUS and advancement through the femoral vein to the jugular vein in subjects with difficult to control hypertension. The procedure duration is expected to range between 60 to 90 minutes and is performed under fluoroscopic and ultrasound image guidance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as assessed by incidence of major adverse events | Safety assessed as the combined rate of major adverse events defined as all-causes of death, hospitalization for hypertensive crisis not related to confirmed non-adherence with anti-hypertensive medications, and any device or procedure-related serious adverse event. | From procedure to one month post-procedure | 
| Mean reduction in 24-hour ambulatory systolic and diastolic blood pressure |  | Baseline versus six months post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite rate of major adverse events | Safety assessed as the combined rate of major adverse events defined as all-causes of death and hospitalization for hypertensive crisis not related to confirmed non-adherence with anti-hypertensive medications | At 6, 12, 18, and 24 months post-procedure | 
| Mean reduction in office systolic and diastolic blood pressure, and home systolic and diastolic blood pressure |  | Baseline versus 3, 6, 12, 18, and 24 months | 
| Proportion of subjects with controlled blood pressure at 6, 12, 18, and 24 months post-procedure | Controlled blood pressure is defined as office blood pressure <140/90 mmHg, mean 24-hr ABP <130/80 mmHg, daytime ABP <135/85 mmHg, and mean nighttime ABP <120/70 mmHg | At 6, 12, 18, and 24 months | 
| Ventricular morphometric improvements from cardiac MRI measurements |  | Screening versus 12 and 24 months |