IntErnational Long-term Follow-up Study of Patients With Uncontrolled HyperTensioN

Study Overview
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Brief Summary
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The purpose of this post market clinical investigation is to further evaluate the safety and performance of the EnligHTN™ Renal Denervation System in the treatment of patients with uncontrolled hypertension.

Detailed Description
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This is a post market, prospective, multicenter, non-randomized, single arm study of the EnligHTN™ Renal Denervation System. Approximately 500 subjects with uncontrolled hypertension will undergo renal artery ablation at approximately 40 investigational sites located internationally and will be followed up to five years post procedure.

Official Title
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IntErnational Non-randomized, Single-arm, Long-term Follow-up Study of Patients With Uncontrolled HyperTensioN

Conditions
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Hypertension, Blood Pressure

Intervention / Treatment
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* Device: EnligHTN


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is ≥ 18 years of age at time of consent Subject must be able and willing to provide written informed consent Subject must be able and willing to comply with the required follow-up schedule Subject has office Systolic Blood Pressure ≥ 140 mmHg at confirmatory visit Subject has a daytime mean Systolic Ambulatory Blood Pressure > 135 mmHg within 90 days prior to procedure Subject has established hypertension (diagnosed ≥12 month prior to baseline) and is on a guideline based drug regimen at a stable and fully tolerated dose consisting of ≥ 3 anti-hypertensive medications (including 1 diuretic) or subject has a documented drug intolerance to 2 or more of the 4 major classes of anti-hypertensives (ACE/ARB, Calcium Channel Blockers, Beta Blockers, or diuretic) and is unable to take 3 anti-hypertensive drugs. Exclusion Criteria: Subject has significant renovascular abnormalities such as renal artery stenosis > 30% Subject has undergone prior renal angioplasty, renal denervation, indwelling renal stents, and/or abdominal aortic stent grafts Subject has hemodynamically significant valvular heart disease as determined by study investigator Subject has a life expectancy less than 12 months, as determined by the Investigator Subject is participating in another clinical study which has the potential to impact their hypertension management (pharmaceutical/device/homeopathic) Subject is pregnant, nursing, or of childbearing potential and is not using adequate contraceptive methods Subject has active systemic infection Subject has renal arteries with diameter(s) < 4 mm in diameter Subject has an estimated GFR <15 mL/min per 1.73 m^2 using the MDRD formula Subject had a renal transplant or is awaiting a renal transplant Subject has blood clotting abnormalities

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| A - EnligHTN for Severe Resistant HTN<br>Office systolic Blood Pressure ≥160 mmHg Subject is taking ≥3 anti-hypertensive medications (including 1 diuretic), or subject has documented drug intolerance to 2 or more of the 4 major classes of anti-hypertensives (ACE/ARB, Calcium Channel Blockers, Beta Blockers, or diuretic) and is unable to take 3 anti-hypertensive drugs. Patient has an estimated GFR ≥45 mL/min per 1.73 m^2 using the Modification of Diet in Renal Disease (MDRD) formula | Device: EnligHTN<br>* Renal artery ablation with EnligHTN system used for all groups<br>|
| B - EnligHTN for Resistant HTN<br>Office systolic Blood Pressure ≥140 mmHg Subject is taking ≥3 anti-hypertensive medications (including 1 diuretic), or subject has documented drug intolerance to 2 or more of the 4 major classes of anti-hypertensives (ACE/ARB, Calcium Channel Blockers, Beta Blockers, or diuretic) and is unable to take 3 anti-hypertensive drugs. Patient has an estimated GFR ≥45 mL/min per 1.73 m^2 using the Modification of Diet in Renal Disease (MDRD) formula | Device: EnligHTN<br>* Renal artery ablation with EnligHTN system used for all groups<br>|
| C - EnligHTN for Resistant HTN & CKD<br>Office systolic Blood Pressure ≥140 mmHg Subject is taking ≥3 anti-hypertensive medications (including 1 diuretic), or subject has documented drug intolerance to 2 or more of the 4 major classes of anti-hypertensives (ACE/ARB, Calcium Channel Blockers, Beta Blockers, or diuretic) and is unable to take 3 anti-hypertensive drugs. Patient has an estimated ≥15 GFR <45 mL/min per 1.73 m^2 using the Modification of Diet in Renal Disease (MDRD) formula | Device: EnligHTN<br>* Renal artery ablation with EnligHTN system used for all groups<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Reduction in Office Systolic Blood Pressure From Baseline to 6 Months | Office blood pressure corresponds to the blood pressure measured by the doctor or the nurse/staff in the office or in the clinic during the participant visit. Office Blood Pressure measurements was recorded as the average Blood Pressure of three measurements. If there was a change in medication after the office Blood Pressure assessment was completed an additional set of office Blood Pressure measurements was performed. | Baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Safety: Percentage of Participants With Peri-procedural Events Within 30 Days Post-procedure | The peri-procedural events occurring within 30 days post procedure were summarized as the percentage of the number of participants with peri-procedural events within 30 days post procedure compared to the number of participants at baseline for that population. | 30 days post procedure | 
| Midterm Safety: Percentage of Participants With New Renal Artery Stenosis and/or Aneurysm at Ablation Site at 6 Months | The new renal artery stenosis (>50%) and/or aneurysm at the site of ablation per Renal Artery Imaging (CT/MR) was summarized at each follow-up visit as the percentage of patients who have stenosis and/or aneurysm. Kaplan-meier analysis was performed on the time to the first new renal artery stenosis and/or aneurysm at the site of ablation, as appropriate. | 6 months | 
| Midterm Safety: Mean Change in eGFR (mL/Min/1.73m²) From Confirmatory Visit to 6 Months | Renal function change based on eGFR was summarized by computing the change of the eGFR at each follow-up visit compared to baseline for each patient with data available in both time points and calculating the mean and standard deviation of the eGFR change at those intervals. | Confirmatory visit to 6 months | 
| Long Term Safety: Percentage of Participants With New Renal Artery Stenosis and/or Aneurysm at Ablation Site at 2 Years | The new renal artery stenosis (>50%) and/or aneurysm at the site of ablation per RenalArtery Imaging (CT/MR) was summarized at each follow-up visit as the percentage of patients who have stenosis and/or aneurysm. Kaplan-meier analysis was performed onthe time to the first new renal artery stenosis and/or aneurysm at the site of ablation, as appropriate. | 2 years | 
| Long Term Safety: Percentage of Participants With New Renal Artery Stenosis and/or Aneurysm at Ablation Site at 5 Years | The new renal artery stenosis (>50%) and/or aneurysm at the site of ablation per RenalArtery Imaging (CT/MR) was summarized at each follow-up visit as the percentage of patients who have stenosis and/or aneurysm. Kaplan-meier analysis was performed onthe time to the first new renal artery stenosis and/or aneurysm at the site of ablation, as appropriate. | 5 years | 
| Long Term Safety: Mean Change in eGFR (mL/Min/1.73m²) From Confirmatory Visit to 2 Years | Renal function change based on eGFR was summarized by computing the change of the eGFR at each follow-up visit compared to baseline for each patient with data available in both time points and calculating the mean and standard deviation of the eGFR change at those intervals. | Confirmatory visit to 2 years | 
| Long Term Safety: Mean Change in eGFR (mL/Min/1.73m²) From Confirmatory Visit to 5 Years | Renal function change based on eGFR was summarized by computing the change of the eGFR at each follow-up visit compared to baseline for each patient with data available in both time points and calculating the mean and standard deviation of the eGFR change at those intervals. | Confirmatory visit to 5 years | 
| Mean Change in Office Diastolic Blood Pressure From Baseline to 4 Years Post Denervation | Office blood pressure corresponds to the blood pressure measured by the doctor or the nurse/staff in the office or in the clinic during the participant visit. Office Blood Pressure measurements was recorded as the average Blood Pressure of three measurements. If there was a change in medication after the office Blood Pressure assessment was completed an additional set of office Blood Pressure measurements was performed. | Baseline to 4 years | 
| Mean Change in Office Diastolic Blood Pressure From Baseline to 5 Years Post Denervation | Office blood pressure corresponds to the blood pressure measured by the doctor or the nurse/staff in the office or in the clinic during the participant visit. Office Blood Pressure measurements was recorded as the average Blood Pressure of three measurements. If there was a change in medication after the office Blood Pressure assessment was completed an additional set of office Blood Pressure measurements was performed. | Baseline to 5 years | 
| Mean Change in Ambulatory Systolic Blood Pressure From Baseline to 6 Months | 24-hour Ambulatory Blood Pressure measurements were taken according to Standard Joint National Committee VII Guidelines / ESC and ESH Guidelines at each follow-up visit. In the 24-hour blood pressure monitoring, the blood pressure of patient was measured every 30 minutes during the daytime and every 60 minutes during the night time. When using ABP, it was ensured that at least two measurements per hour are taken during the person's usual waking hours and 1 measurement per hour are taken during the person's usual night time hours. The average value of at least 14 measurements taken during the person's usual waking hours and average of at least 8 measurements taken during the person's usual sleeping hours were used for calculation of mean value. | Baseline to 6 months | 
| Mean Change in Ambulatory Diastolic Blood Pressure From Baseline to 6 Months | 24-hour Ambulatory Blood Pressure measurements were taken according to Standard Joint National Committee VII Guidelines / ESC and ESH Guidelines at each follow-up visit. In the 24-hour blood pressure monitoring, the blood pressure of patient was measured every 30 minutes during the daytime and every 60 minutes during the night time. When using ABP, it was ensured that at least two measurements per hour are taken during the person's usual waking hours and 1 measurement per hour are taken during the person's usual night time hours. The average value of at least 14 measurements taken during the person's usual waking hours and average of at least 8 measurements taken during the person's usual sleeping hours were used for calculation of mean value. | Baseline to 6 months | 
| Mean Change in Office Diastolic Blood Pressure From Baseline to 6 Months | Office blood pressure corresponds to the blood pressure measured by the doctor or the nurse/staff in the office or in the clinic during the participant visit. Office Blood Pressure measurements was recorded as the average Blood Pressure of three measurements. If there was a change in medication after the office Blood Pressure assessment was completed an additional set of office Blood Pressure measurements was performed. | Baseline to 6 months | 
| Percentage of Participants Achieved Office Systolic Blood Pressure < 140 mmHg at 6 Months | The percentage of participants achieved office systolic blood pressure <140 mmHg at 6 months visit was computed as the percentage of the ratio of number of participants who achievied office systolic blood pressure <140 mmHg at 6 months visit to the number of participants with data available in 6 months visit. | 6 months | 
| Mean Change in Office Systolic Blood Pressure From Baseline to 1 Year Post Denervation | Office blood pressure corresponds to the blood pressure measured by the doctor or the nurse/staff in the office or in the clinic during the participant visit. Office Blood Pressure measurements was recorded as the average Blood Pressure of three measurements. If there was a change in medication after the office Blood Pressure assessment was completed an additional set of office Blood Pressure measurements was performed. | Baseline to 1 year | 
| Mean Change in Office Systolic Blood Pressure From Baseline to 2 Years Post Denervation | Office blood pressure corresponds to the blood pressure measured by the doctor or the nurse/staff in the office or in the clinic during the participant visit. Office Blood Pressure measurements was recorded as the average Blood Pressure of three measurements. If there was a change in medication after the office Blood Pressure assessment was completed an additional set of office Blood Pressure measurements was performed. | Baseline to 2 years | 
| Mean Change in Office Systolic Blood Pressure From Baseline to 3 Years Post Denervation | Office blood pressure corresponds to the blood pressure measured by the doctor or the nurse/staff in the office or in the clinic during the participant visit. Office Blood Pressure measurements was recorded as the average Blood Pressure of three measurements. If there was a change in medication after the office Blood Pressure assessment was completed an additional set of office Blood Pressure measurements was performed. | Baseline to 3 years | 
| Mean Change in Office Systolic Blood Pressure From Baseline to 4 Years Post Denervation | Office blood pressure corresponds to the blood pressure measured by the doctor or the nurse/staff in the office or in the clinic during the participant visit. Office Blood Pressure measurements was recorded as the average Blood Pressure of three measurements. If there was a change in medication after the office Blood Pressure assessment was completed an additional set of office Blood Pressure measurements was performed. | Baseline to 4 years | 
| Mean Change in Office Systolic Blood Pressure From Baseline to 5 Years Post Denervation | Office blood pressure corresponds to the blood pressure measured by the doctor or the nurse/staff in the office or in the clinic during the participant visit. Office Blood Pressure measurements was recorded as the average Blood Pressure of three measurements. If there was a change in medication after the office Blood Pressure assessment was completed an additional set of office Blood Pressure measurements was performed. | Baseline to 5 years | 
| Mean Change in Office Diastolic Blood Pressure From Baseline to 1 Year Post Denervation | Office blood pressure corresponds to the blood pressure measured by the doctor or the nurse/staff in the office or in the clinic during the participant visit. Office Blood Pressure measurements was recorded as the average Blood Pressure of three measurements. If there was a change in medication after the office Blood Pressure assessment was completed an additional set of office Blood Pressure measurements was performed. | Baseline to 1 year | 
| Mean Change in Office Diastolic Blood Pressure From Baseline to 2 Years Post Denervation | Office blood pressure corresponds to the blood pressure measured by the doctor or the nurse/staff in the office or in the clinic during the participant visit. Office Blood Pressure measurements was recorded as the average Blood Pressure of three measurements. If there was a change in medication after the office Blood Pressure assessment was completed an additional set of office Blood Pressure measurements was performed. | Baseline to 2 years | 
| Mean Change in Office Diastolic Blood Pressure From Baseline to 3 Years Post Denervation | Office blood pressure corresponds to the blood pressure measured by the doctor or the nurse/staff in the office or in the clinic during the participant visit. Office Blood Pressure measurements was recorded as the average Blood Pressure of three measurements. If there was a change in medication after the office Blood Pressure assessment was completed an additional set of office Blood Pressure measurements was performed. | Baseline to 3 years | 
| Mean Change in Ambulatory Systolic Blood Pressure From Baseline to 1 Year Post Denervation | 24-hour Ambulatory Blood Pressure measurements were taken according to Standard Joint National Committee VII Guidelines / ESC and ESH Guidelines at each follow-up visit. In the 24-hour blood pressure monitoring, the blood pressure of patient was measured every 30 minutes during the daytime and every 60 minutes during the night time. When using ABP, it was ensured that at least two measurements per hour are taken during the person's usual waking hours and 1 measurement per hour are taken during the person's usual night time hours. The average value of at least 14 measurements taken during the person's usual waking hours and average of at least 8 measurements taken during the person's usual sleeping hours were used for calculation of mean value. | Baseline to 1 year | 
| Mean Change in Ambulatory Systolic Blood Pressure From Baseline to 2 Years Post Denervation | 24-hour Ambulatory Blood Pressure measurements were taken according to Standard Joint National Committee VII Guidelines / ESC and ESH Guidelines at each follow-up visit. In the 24-hour blood pressure monitoring, the blood pressure of patient was measured every 30 minutes during the daytime and every 60 minutes during the night time. When using ABP, it was ensured that at least two measurements per hour are taken during the person's usual waking hours and 1 measurement per hour are taken during the person's usual night time hours. The average value of at least 14 measurements taken during the person's usual waking hours and average of at least 8 measurements taken during the person's usual sleeping hours were used for calculation of mean value. | Baseline to 2 years | 
| Mean Change in Ambulatory Systolic Blood Pressure From Baseline to 3 Years Post Denervation | 24-hour Ambulatory Blood Pressure measurements were taken according to Standard Joint National Committee VII Guidelines / ESC and ESH Guidelines at each follow-up visit. In the 24-hour blood pressure monitoring, the blood pressure of patient was measured every 30 minutes during the daytime and every 60 minutes during the night time. When using ABP, it was ensured that at least two measurements per hour are taken during the person's usual waking hours and 1 measurement per hour are taken during the person's usual night time hours. The average value of at least 14 measurements taken during the person's usual waking hours and average of at least 8 measurements taken during the person's usual sleeping hours were used for calculation of mean value. | Baseline to 3 years | 
| Mean Change in Ambulatory Systolic Blood Pressure From Baseline to 4 Years Post Denervation | 24-hour Ambulatory Blood Pressure measurements were taken according to Standard Joint National Committee VII Guidelines / ESC and ESH Guidelines at each follow-up visit. In the 24-hour blood pressure monitoring, the blood pressure of patient was measured every 30 minutes during the daytime and every 60 minutes during the night time. When using ABP, it was ensured that at least two measurements per hour are taken during the person's usual waking hours and 1 measurement per hour are taken during the person's usual night time hours. The average value of at least 14 measurements taken during the person's usual waking hours and average of at least 8 measurements taken during the person's usual sleeping hours were used for calculation of mean value. | Baseline to 4 years | 
| Mean Change in Ambulatory Systolic Blood Pressure From Baseline to 5 Years Post Denervation | 24-hour Ambulatory Blood Pressure measurements were taken according to Standard Joint National Committee VII Guidelines / ESC and ESH Guidelines at each follow-up visit. In the 24-hour blood pressure monitoring, the blood pressure of patient was measured every 30 minutes during the daytime and every 60 minutes during the night time. When using ABP, it was ensured that at least two measurements per hour are taken during the person's usual waking hours and 1 measurement per hour are taken during the person's usual night time hours. The average value of at least 14 measurements taken during the person's usual waking hours and average of at least 8 measurements taken during the person's usual sleeping hours were used for calculation of mean value. | Baseline to 5 years | 
| Mean Change in Ambulatory Diastolic Blood Pressure From Baseline to 1 Year Post Denervation | 24-hour Ambulatory Blood Pressure measurements were taken according to Standard Joint National Committee VII Guidelines / ESC and ESH Guidelines at each follow-up visit. In the 24-hour blood pressure monitoring, the blood pressure of patient was measured every 30 minutes during the daytime and every 60 minutes during the night time. When using ABP, it was ensured that at least two measurements per hour are taken during the person's usual waking hours and 1 measurement per hour are taken during the person's usual night time hours. The average value of at least 14 measurements taken during the person's usual waking hours and average of at least 8 measurements taken during the person's usual sleeping hours were used for calculation of mean value. | Baseline to 1 year | 
| Mean Change in Ambulatory Diastolic Blood Pressure From Baseline to 2 Years Post Denervation | 24-hour Ambulatory Blood Pressure measurements were taken according to Standard Joint National Committee VII Guidelines / ESC and ESH Guidelines at each follow-up visit. In the 24-hour blood pressure monitoring, the blood pressure of patient was measured every 30 minutes during the daytime and every 60 minutes during the night time. When using ABP, it was ensured that at least two measurements per hour are taken during the person's usual waking hours and 1 measurement per hour are taken during the person's usual night time hours. The average value of at least 14 measurements taken during the person's usual waking hours and average of at least 8 measurements taken during the person's usual sleeping hours were used for calculation of mean value. | Baseline to 2 years | 
| Mean Change in Ambulatory Diastolic Blood Pressure From Baseline to 3 Years Post Denervation | 24-hour Ambulatory Blood Pressure measurements were taken according to Standard Joint National Committee VII Guidelines / ESC and ESH Guidelines at each follow-up visit. In the 24-hour blood pressure monitoring, the blood pressure of patient was measured every 30 minutes during the daytime and every 60 minutes during the night time. When using ABP, it was ensured that at least two measurements per hour are taken during the person's usual waking hours and 1 measurement per hour are taken during the person's usual night time hours. The average value of at least 14 measurements taken during the person's usual waking hours and average of at least 8 measurements taken during the person's usual sleeping hours were used for calculation of mean value. | Baseline to 3 years | 
| Mean Change in Ambulatory Diastolic Blood Pressure From Baseline to 4 Years Post Denervation | 24-hour Ambulatory Blood Pressure measurements were taken according to Standard Joint National Committee VII Guidelines / ESC and ESH Guidelines at each follow-up visit. In the 24-hour blood pressure monitoring, the blood pressure of patient was measured every 30 minutes during the daytime and every 60 minutes during the night time. When using ABP, it was ensured that at least two measurements per hour are taken during the person's usual waking hours and 1 measurement per hour are taken during the person's usual night time hours. The average value of at least 14 measurements taken during the person's usual waking hours and average of at least 8 measurements taken during the person's usual sleeping hours were used for calculation of mean value. | Baseline to 4 years | 
| Mean Change in Ambulatory Diastolic Blood Pressure From Baseline to 5 Years Post Denervation | 24-hour Ambulatory Blood Pressure measurements were taken according to Standard Joint National Committee VII Guidelines / ESC and ESH Guidelines at each follow-up visit. In the 24-hour blood pressure monitoring, the blood pressure of patient was measured every 30 minutes during the daytime and every 60 minutes during the night time. When using ABP, it was ensured that at least two measurements per hour are taken during the person's usual waking hours and 1 measurement per hour are taken during the person's usual night time hours. The average value of at least 14 measurements taken during the person's usual waking hours and average of at least 8 measurements taken during the person's usual sleeping hours were used for calculation of mean value. | Baseline to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal Denervation, Renal artery, EnligHTN™ Renal Denervation System, Renal Artery Ablation