Hypertension
Conditions
Brief summary
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.
Interventions
DEVICEbaroloop System
vagal nerve stimulation
Sponsors
Avania
neuroloop GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 18 years or older and less than 80 years of age. 2. 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. 3. 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. 4. 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. 5. 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. 6. Willingness and ability to comply with follow-up requirements. 7. Signed informed consent.
Exclusion criteria
1. 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). 2. Any patient with a history of injury to the vagus nerve or its branches (e.g., the recurrent laryngeal nerve). 3. Secondary causes of hypertension. 4. Calculated eGFR \< 30 mL/min/1.73m2. 5. Type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus (HbA1c \> 10%). 6. One or more episodes of orthostatic hypotension in the past year 7. Requirement for chronic oxygen therapy or mechanical ventilation. 8. Untreated (no CPAP therapy) sleep apnea (AHI \> 15) 9. Morbid obesity, defined as Body Mass Index \>40 kg/m2 or arm circumference 46 cm. 10. Pacemaker and/or implantable defibrillators. 11. History of transient ischemic accident or cerebrovascular accident during six (6) months prior to screening. 12. Symptomatic carotid artery disease or \> 70% occlusion of either carotid artery; any carotid malformation or lesion, a carotid bruit or other abnormal carotid sound. 13. 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). 14. Limited mobility of the neck secondary to vertebral disease or prior vertebral surgery, including patients who wear a cervical support. 15. 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. 16. Cardiac arrythmias (atrial fibrillation, atrial flutter, etc.) that require anticoagulation or interfere with a consistent measurement of blood pressure. 17. Syncope in the last 6 months. 18. History of bleeding disorders, thrombocytopenia, hemophilia or significant anemia (hemoglobin (Hgb) \< 10 gm/dl). 19. Current anticoagulation therapy (excluding antiplatelet therapy with aspirin as a sole therapy). 20. Works night shifts. 21. History of unresolved drug or alcohol use. 22. Active treatment of a psychiatric ailment. 23. Life expectancy of less than 12 months due to other disease. 24. Subject has a condition that, in the opinion of the investigator, precludes participation, including willingness to comply, with all follow-up procedures. 25. Participation in another clinical study for which follow-up is currently on-going. 26. Women who are of child-bearing age or who have the potential to become pregnant 27. 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. 28. Baroreflex failure or autonomic neuropathy 29. Symptomatic, uncontrolled bradyarrhythmias 30. Atrioventricular block of any grade 31. Patients who are treated with Pacemaker and/or implantable defibrillators 32. Presence of a vagus stimulator 33. Patients who expect to require magnetic resonance imaging (MRI) of the cervical area 34. Occupational exposure to high levels of non-ionizing radiation that may interfere with therapy 35. Patients with a limited ability to read, understand and execute adjustment procedures (for example, persons suffering from dementia). 36. Likely exposure to diathermy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Major Adverse Event (MAE) Rate | at 6 months post-treatment | The MAE rate is calculated based on the number of participants that either died, were hospitalized for hypertensive crisis after the first titration visit, or experienced any device or procedure-related serious adverse events. |
| Feasibility - Device Placement and Vagal Nerve Stimulation | Day 14 or Day 21 post-implantation | Feasibility was calculated based on the number of participants in whom the baroloop system was successfully placed around a vagal nerve and stimulation of the nerve was possible. Stimulation of the vagus nerve was attempted for the first time after either 14 or 21 days; depending on the healing progress of the participant after the surgery. Therefore, feasibility (ability to place the device and ability to stimulate the nerve after the surgery) was either confirmed after 14 days or 21 days, depending on the healing progress of the participant after the surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite MAE Rate | 1, 3, 12, 18 and 24 months | he MAE consists of all causes of death, hospitalization for hypertensive crisis post-titration, and any device or procedure-related serious adverse events |
| Change in Office Blood Pressure | 1, 3, 6, 12, 18 and 24 months | Mean change in office systolic and diastolic blood pressure |
| Change in Blood Pressure | at the time of implantation | Change in blood pressure recorded during intraoperative stimulation |
| Quality of Life Evaluation - Short Form (36) Health Survey | Baseline, 1, 3, 6, 12, 18 and 24 months | 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. |
| Change in Antihypertensive Drugs/Dosages | 1, 3, 6, 12, 18 and 24 months | Changes in antihypertensive drugs/dosages post-implantation as analyzed by Daily Defined Dosages (WHO Definition) and total medications |
| Change in 24-hour ABPM | 1, 3, 6, 12, 18 and 24 months | Mean change of 24-hour ambulatory systolic and diastolic blood pressure post-treatment versus baseline |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Investigational Device Subjects implanted with the baroloop device
baroloop System: vagal nerve stimulation | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Device failure in all 4 patients | 4 |
Baseline characteristics
| Characteristic | Investigational Device |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment Netherlands | 4 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 3 / 4 |
| serious Total, serious adverse events | 4 / 4 |
Outcome results
Primary
Composite Major Adverse Event (MAE) Rate
The MAE rate is calculated based on the number of participants that either died, were hospitalized for hypertensive crisis after the first titration visit, or experienced any device or procedure-related serious adverse events.
Time frame: at 6 months post-treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Investigational Device | Composite Major Adverse Event (MAE) Rate | 4 Participants |
Primary
Feasibility - Device Placement and Vagal Nerve Stimulation
Feasibility was calculated based on the number of participants in whom the baroloop system was successfully placed around a vagal nerve and stimulation of the nerve was possible. Stimulation of the vagus nerve was attempted for the first time after either 14 or 21 days; depending on the healing progress of the participant after the surgery. Therefore, feasibility (ability to place the device and ability to stimulate the nerve after the surgery) was either confirmed after 14 days or 21 days, depending on the healing progress of the participant after the surgery.
Time frame: Day 14 or Day 21 post-implantation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Investigational Device | Feasibility - Device Placement and Vagal Nerve Stimulation | 4 Participants |
Secondary
Change in 24-hour ABPM
Mean change of 24-hour ambulatory systolic and diastolic blood pressure post-treatment versus baseline
Time frame: 1, 3, 6, 12, 18 and 24 months
Secondary
Change in Antihypertensive Drugs/Dosages
Changes in antihypertensive drugs/dosages post-implantation as analyzed by Daily Defined Dosages (WHO Definition) and total medications
Time frame: 1, 3, 6, 12, 18 and 24 months
Secondary
Change in Blood Pressure
Change in blood pressure recorded during intraoperative stimulation
Time frame: at the time of implantation
Secondary
Change in Office Blood Pressure
Mean change in office systolic and diastolic blood pressure
Time frame: 1, 3, 6, 12, 18 and 24 months
Secondary
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
Time frame: 1, 3, 12, 18 and 24 months
Secondary
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.
Time frame: Baseline, 1, 3, 6, 12, 18 and 24 months