Hypertension
Conditions
Keywords
Hypertension, Renal Denervation
Brief summary
To demonstrate that non-invasive renal denervation is safe and shows a net difference in blood pressure reduction when compared to sham in subjects with uncontrolled hypertension.
Detailed description
This study is a sham controlled, double blind study of subjects with uncontrolled hypertension consisting of two arms, sham and therapy. Bilateral renal denervation will be performed non-invasively using the Kona Medical Surround Sound System which delivers focused ultrasound therapy to ablate the nerves surrounding the renal artery utilizing real time ultrasound for targeting and tracking.
Interventions
DEVICEInvestigational Therapy (Surround Sound)
DEVICESham Control
Sponsors
Kona Medical Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Subject is at least 18 years of age and no more than 90 years of age 2. Average SBP ≥ 160 mmHg 3. 24 hour average ABPM daytime SBP ≥ 135 mmHg. 4. No medication changes for a minimum of 1 months prior to screening. 5. At minimum, subject must be on at least three antihypertensive medications, with one being a diuretic, and each must meet one or more of the following full dose criteria: 1. Highest labeled dose according to medication's labeling; 2. Highest usual dose per clinical guidelines JNC-7; 3. Highest tolerated dose; and/or 4. Highest appropriate dose for the subject per the PI's clinical judgment. 6. Subject has two functioning kidneys. 7. Subject has an eGFR value of ≥ 30 ml/min/1.73 m² (MDRD formula).
Exclusion criteria
1. Subject has any secondary cause of hypertension 2. Subject has evidence of clinically significant renal artery stenosis as determined by flow rate, velocity and Doppler analysis on ultrasound 3. Subject has kidney stones that are of a size and location that are determined at discretion of the investigator to potentially interfere with treatment 4. Subject has a history of intra-abdominal surgery within the past six months 5. Subject has heterogeneities in the kidney such as large cysts or tumors that are determined at discretion of the investigator to potentially interfere with treatment. 6. Stenotic valvular heart disease for which BP reduction would be hazardous as determined by referring physician. 7. MI, unstable angina, or CVA in the prior 6 months. 8. Known severe primary pulmonary HTN 9. Subject has a history of myocardial infarction, unstable angina pectoris, or cerebrovascular accident within the last six months. 10. Subject has hemodynamically significant valvular heart disease. 11. Subject has BMI over 40 km/m\^2 12. Subject has a target treatment depth over 13 cm. 13. Subject has anatomy that precludes treatment with the Kona Medical Surround Sound System. 14. Subject is pregnant, nursing, or intends to become pregnant during the trial period. 15. Subject is currently enrolled in other potentially confounding research. 16. Subject has any condition that, at the discretion of the investigator, would preclude participation in the trial. 17. Subject is unable, or unwilling, to comply with the protocol-required follow-up schedule
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety at 6 weeks follow-up | 6 weeks | Safety will be assessed by incidence of Major Adverse Events (MAE), defined as a composite of the following events at 6-weeks follow-up. * All cause mortality; * End-stage Renal Disease defined as eGFR \< 15 ml/min or need for renal replacement therapy * Hospitalization for hypertensive crisis not related to confirmed non-adherence with medications as assessed by toxicological and other medical analyses and testing. OR \- New renal artery stenosis \> 70% confirmed by angiography within 6 months of randomization |
| Change in OBP | 6 months | Change in Office Systolic Blood Pressure (OBP) as measured from screening visit one to the 6 month post randomization follow-up visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in ABPM | 6 months | Change in average 24-hour ambulatory blood pressure from screening to the 6 month follow-up visit |
Other
| Measure | Time frame | Description |
|---|---|---|
| Reduction in anti-hypertensive medications | 6 months | Incidence of reductions in the number of anti-hypertensive medications and reductions in the doses of anti-hypertensive medications. |
| Chronic Safety | 6 months | Chronic safety is assessed and compared between the control and treatment groups at 6 months post-randomization as follows: * Cardiovascular/Renal Death; * End stage Renal Disease * Increase in serum creatinine of \> 50%; and * Hospitalization for hypertensive crisis not confirmed non-adherence with medications. |
| Changes in HR | 6 months | Changes in HR (as measured by OBP and ABPM) through the 6 month follow-up period. |
| Changes in OBP | 24 months | Changes in OBP from screening to the 12, 18, and 24 month follow-up periods. |
| Reduction in blood pressure | 6 months | Reduction in systolic and diastolic blood pressure as compared between groups at time points through the 6 month follow-up period for interval differences of 10,15 and 20 mmHg. |
| Incidence of achieving target OBP | 6 months | Incidence of achieving target OBP (\< 140 mmHg) through the 6 month follow-up period. |
Countries
Australia, Austria, Colombia, Czechia, Germany, New Zealand, Poland, United Kingdom
Contacts
Primary ContactOmar Dawood
Outcome results
None listed