Uncontrolled Stage 2 Hypertension
Conditions
Brief summary
This is a prospective, multicenter, non-randomized, open-label clinical study of the safety and performance of the TIVUS™ System in subjects with uncontrolled stage 2 hypertension in order to assess the safety and effectiveness of the TIVUS™ System when used for renal artery denervation. The study will assess the acute and chronic safety of the procedure as well as the reduction in 24-hour ambulatory mean systolic blood pressure from baseline to 3 months after the procedure.
Detailed description
Nearly half of adults in the United States (108 million, or 45%) have hypertension defined as a systolic blood pressure ≥ 130 mm Hg or a diastolic blood pressure ≥ 80 mm Hg or are taking medication for hypertension. Hypertension is associated with cardiovascular and renal pathologies and leads to death if not treated appropriately. The cardiovascular risk factor doubles with each 20/10 mm Hg elevation in BP values above 115/75 mm Hg. The current first-line therapy for hypertension involves change in life-style (i.e., diet and exercise) and various medications. However, only about 1 in 4 treated adults (24%) with hypertension have their condition under control. Thus, they are at increased risk for the major side effects of chronically elevated blood pressure, myocardial infarction, stroke, renal disease and heart failure. High blood pressure was a primary or contributing cause of death for more than 494,873 people in the United States in 2018, and was estimated to affect around 1.13 billion people worldwide and resulted in approximately 10 million deaths worldwide, in 2015. About half of adults (45%) with uncontrolled hypertension have a blood pressure of 140/90 mm Hg or higher, now defined as Stage 2 hypertension. This includes 37 million U.S. adults. About 30 million adults are recommended to take medication. Almost two out of three of this group (19 million) have a blood pressure of 140/90 mm Hg or higher. The other 17 million adults are taking medications but are unable to lower their blood pressure below 140/90 mm Hg and are thus at increased risk for the risks associated with uncontrolled high blood pressure9. High blood pressure costs the United States about $131 billion each year, averaged over 12 years from 2003 to 2014. In the past decade, several devices were developed in order to target the autonomic nervous system and lower BP in patients with uncontrolled hypertension. These devices aim to provide additional treatment option for patients who do not respond to antihypertensive medication. These devices target other BP regulating mechanisms such as baroreflex activation, deep brain stimulation carotid body ablation, direct vagus nerve stimulation, cardiac neuromodulation, central iliac arteriovenous coupler as well as other devices are currently under research, however, there is no medical device that has been approved so far. The Therapeutic Intra Vascular UltraSound (TIVUS™) System is designed for renal artery nerve ablation using transluminal ultrasound (US). The TIVUS™ System is a high intensity, non-focused, ultrasound catheter system, which enables remote, localized, controlled, and repeatable thermal modulation of nerves adjacent to arterial vessel wall for performing safe and effective therapeutic artery sympathetic denervation. The ultrasonic energy is transmitted from a catheter positioned within the artery lumen, while avoiding direct contact with the artery wall.
Interventions
DEVICERenal denervation
The TIVUS system will be used for renal denervation
Sponsors
SoniVie Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, multicenter, non-randomized, open-label clinical study
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Written informed consent to participate in the study obtained from the patient, according to local regulations, prior to initiation of any study mandated procedure. 2. Male or female, ≥ 18 years of age and ≤ 80 years of age at the time of screening. 3. Individual has office systolic blood pressure (SBP) ≥ 140 mm Hg but \< 180 mm Hg, and a diastolic blood pressure (DBP) ≥ 90 mm Hg but \< 110 mm Hg based on an average of 3 office seated blood pressure readings measured by a manual, automated or semi-automated validated BP monitor, on current medications. 4. Documented mean daytime ABPM systolic blood pressure (SBP) ≥ 135 mm Hg but \< 180 mm Hg, after a 4 week stabilization period. 5\. Patient is either on at least one anti-hypertensive medication at maximal tolerated dose with a medically documented intolerance to one or more medications, or on three medications where one is a diuretic. 6\. Patient is willing and expected to maintain their anti-hypertensive medication regimen for at least 3 months. 7\. Patient is able and willing to comply with all study procedures.
Exclusion criteria
1. Patient has been previously diagnosed with abnormal renal artery anatomy and/or renal anatomy such as single kidney, other renal development anomaly such as ectopic or horseshoe kidney, or polycystic kidney disease precluding renal denervation therapy as detailed in the angiographic
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | from baseline to 1 month post procedure | acute treatment related adverse events including including all-cause mortality, acute kidney injury, significant embolic event, renal artery perforation or dissection requiring intervention, vascular complications, stroke, myocardial infarction, or transient ischemic attack, deterioration in renal function end-stage renal failure, hospital admission for hypertensive crisis not related to confirmed nonadherence with medications or the protocol, new renal artery stenosis of more than 70% and major access site complications or cardiovascular complications |
| Change in mean daytime ambulatory systolic BP | From baseline to 3 months post procedure | Reduction in daytime ambulatory mean systolic blood pressure from baseline to 3 months after the procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in mean 24-hr ambulatory systolic and diastolic bp | 3, 6, 12, 24, 36 months | Reduction of 24-hour ambulatory mean systolic and diastolic blood pressure from baseline |
| Change in mean 24-hr ambulatory diastolic bp | 3 months | Reduction of 24-hour ambulatory mean diastolic blood pressure from baseline |
| Change in mean daytime ambulatory systolic bp | 6, 12, 24, 36 months | Reduction of daylight ambulatory mean systolic blood pressure from baseline |
| Change in mean nighttime ambulatory systolic and diastolic bp | 3, 6, 12, 24, 36 months | Reduction of nighttime ambulatory mean systolic and diastolic blood pressure from baseline |
| Change in mean office systolic and diastolic BP | 3, 6, 12, 24, 36 months | Reduction of office mean systolic and diastolic blood pressure from baseline |
| Change in mean 24-hr ambulatory pulse | 3, 6, 12, 24, 36 months | Reduction in mean 24-hour ambulatory pulse pressure from baseline |
| Rate of patients achieving target 24-hr ambulatory mean systolic BP | 3, 6, 12, 24, 36 months | Number of patients achieving target 24-hour ambulatory mean systolic blood pressure (\<130 mm Hg) |
| Rate of patients achieving target office systolic BP | 3, 6, 12, 24, 36 months | Number of patients achieving target office systolic blood pressure (\<140 mm Hg) |
| Change in number of antihypertensive medications taken | 6, 12 months | Reduction in the number of antihypertensive medications taken and/or the dose taken |
| Percentage of patients who respond to treatment | 3, 6, 12 months | Percentage of patients who respond to the treatment, with response defined as a reduction of at least 10mm in mean 24-hour ambulatory systolic blood pressure |
| Incidence of hypertensive or hypotensive emergency episodes | 3, 6, 12 months | Incidence of hypertensive or hypotensive emergency episodes resulting in hospitalization |
| Change in renal function based on laboratory parameters | 3, 6, 12 months | Changes in renal function, based on laboratory parameters such as eGFR (CKD-EPI) and serum creatinine |
| Change in renal function based on artery stenosis | 6, 12 months | Changes in renal function, based on artery stenosis (\>70%) |
| Incidence of heart failure | 3, 6, 12 months | Episodes of heart failure events |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAjay Kirtane, MD
Columbia University/NYPH
Outcome results
None listed