The Baroloop Study

Study Overview
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Brief Summary
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The baroloop Study is a non-randomized, prospective, single-arm, multi center First in Human (FIH) study with the primary objective being the assessment of the safety and feasibility of using the baroloop System in subjects with uncontrollable hypertension. The secondary objective is to document the effect of the baroloop device on the blood pressure and quality of life in subjects with hypertension. Up to 10 subjects will be enrolled in up to 3 sites in Europe.

Official Title
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A First in Human Study of Feasibility of Baroloop: The Baroloop Study

Conditions
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Hypertension

Intervention / Treatment
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* Device: baroloop System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or older and less than 80 years of age. Persistent office systolic blood pressure (SBP) ≥ 140 mm Hg and diastolic blood pressure (DBP) > 90 mm Hg on antihypertensive medicines on two visits separated by a minimum of four weeks. Mean 24-hour systolic ABPM ≥ 130 mm Hg and mean 24 hour diastolic ABPM ≥ 80 mm Hg conducted after direct observed therapy to confirm that antihypertensive medicines were taken as prescribed during the ABPM measurement. Stable drug regimen of 4 antihypertensive medicines consisting of a renin-angiotensin blocker(ACE) or Angiotensin II Receptor Blocker (ARBs), a calcium channel blocker (CCB), a diuretic and spironolactone for 4 weeks at treatment. If spironolactone is not tolerated, the regimen must include instead the addition of further diuretic therapy with either eplerenone, amiloride, higher-dose thiazide/thiazide-like diuretic or a loop diuretic, or the addition of bisoprolol or doxazosin. If none of these medicines are tolerated, then patients on a 3-drug regimen may be included. The Investigator has confirmed that the patient has already tried and/or is not suitable for treatment with currently CE-marked device-based therapies for resistant hypertension as an alternative to baroloop therapy. Willingness and ability to comply with follow-up requirements. Signed informed consent. Exclusion Criteria: Any patient in whom access to the vagal nerve is limited by the size of the vagus (a size not compatible with the baroloop cuff). Any patient with a history of injury to the vagus nerve or its branches (e.g., the recurrent laryngeal nerve). Secondary causes of hypertension. Calculated eGFR < 30 mL/min/1.73m2. Type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus (HbA1c > 10%). One or more episodes of orthostatic hypotension in the past year Requirement for chronic oxygen therapy or mechanical ventilation. Untreated (no CPAP therapy) sleep apnea (AHI > 15) Morbid obesity, defined as Body Mass Index >40 kg/m2 or arm circumference 46 cm. Pacemaker and/or implantable defibrillators. History of transient ischemic accident or cerebrovascular accident during six (6) months prior to screening. Symptomatic carotid artery disease or > 70% occlusion of either carotid artery; any carotid malformation or lesion, a carotid bruit or other abnormal carotid sound. Prior surgery, radiation therapy or scarring in the neck in the region of the carotid artery (e.g., patients with a tracheostomy, extensive thymectomy or thyroid surgery). Limited mobility of the neck secondary to vertebral disease or prior vertebral surgery, including patients who wear a cervical support. History of heart failure (NYHA class III-IV or ejection fraction < 30%), myocardial infarction, unstable angina, coronary bypass or coronary angioplasty during six (6) months prior to screening. Cardiac arrythmias (atrial fibrillation, atrial flutter, etc.) that require anticoagulation or interfere with a consistent measurement of blood pressure. Syncope in the last 6 months. History of bleeding disorders, thrombocytopenia, hemophilia or significant anemia (hemoglobin (Hgb) < 10 gm/dl). Current anticoagulation therapy (excluding antiplatelet therapy with aspirin as a sole therapy). Works night shifts. History of unresolved drug or alcohol use. Active treatment of a psychiatric ailment. Life expectancy of less than 12 months due to other disease. Subject has a condition that, in the opinion of the investigator, precludes participation, including willingness to comply, with all follow-up procedures. Participation in another clinical study for which follow-up is currently on-going. Women who are of child-bearing age or who have the potential to become pregnant Resting heart rate of <40 beats/min for patients on beta blockers or <60 beats/min for all other patients, confirmed at both baseline visits. Baroreflex failure or autonomic neuropathy Symptomatic, uncontrolled bradyarrhythmias Atrioventricular block of any grade Patients who are treated with Pacemaker and/or implantable defibrillators Presence of a vagus stimulator Patients who expect to require magnetic resonance imaging (MRI) of the cervical area Occupational exposure to high levels of non-ionizing radiation that may interfere with therapy Patients with a limited ability to read, understand and execute adjustment procedures (for example, persons suffering from dementia). Likely exposure to diathermy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Investigational Device<br>Subjects implanted with the baroloop device | Device: baroloop System<br>* vagal nerve stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Major Adverse Event (MAE) Rate | The MAE consists of all causes of death, hospitalization for hypertensive crisis post-titration, and any device or procedure-related serious adverse events | at 6 months post-treatment | 
| Feasibility - device placement and vagal nerve stimulation | Feasibility is defined as the ability of the baroloop System to be placed around a vagal nerve and to stimulate the nerve | Day 14 or Day 21 post-implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood pressure | Change in blood pressure recorded during intraoperative stimulation | at the time of implantation | 
| Change in 24-hour ABPM | Mean change of 24-hour ambulatory systolic and diastolic blood pressure post-treatment versus baseline | 1, 3, 6, 12, 18 and 24 months | 
| Composite MAE rate | he MAE consists of all causes of death, hospitalization for hypertensive crisis post-titration, and any device or procedure-related serious adverse events | 1, 3, 12, 18 and 24 months | 
| Change in Office Blood Pressure | Mean change in office systolic and diastolic blood pressure | 1, 3, 6, 12, 18 and 24 months | 
| Change in antihypertensive drugs/dosages | Changes in antihypertensive drugs/dosages post-implantation as analyzed by Daily Defined Dosages (WHO Definition) and total medications | 1, 3, 6, 12, 18 and 24 months | 
| Quality of Life Evaluation - Short Form (36) Health Survey | Quality of Life as measured by the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. | Baseline, 1, 3, 6, 12, 18 and 24 months |