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

Terminated

Conditions: Blood Pressure
Hypertension

Interventions: Device: EnligHTN

Registration Number: NCT01705080

Lead Sponsor: Abbott Medical Devices

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 276

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

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
B - EnligHTN for Resistant HTN	EnligHTN	* 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
C - EnligHTN for Resistant HTN & CKD	EnligHTN	* 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
A - EnligHTN for Severe Resistant HTN	EnligHTN	* 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

Primary Outcome Measures

Name	Time	Method
Mean Reduction in Office Systolic Blood Pressure From Baseline to 6 Months	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.

Secondary Outcome Measures

Name	Time	Method
Acute Safety: Percentage of Participants With Peri-procedural Events Within 30 Days Post-procedure	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.
Midterm Safety: Percentage of Participants With New Renal Artery Stenosis and/or Aneurysm at Ablation Site at 6 Months	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.
Midterm Safety: Mean Change in eGFR (mL/Min/1.73m²) From Confirmatory Visit to 6 Months	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.
Long Term Safety: Percentage of Participants With New Renal Artery Stenosis and/or Aneurysm at Ablation Site at 2 Years	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.
Long Term Safety: Percentage of Participants With New Renal Artery Stenosis and/or Aneurysm at Ablation Site at 5 Years	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.
Long Term Safety: Mean Change in eGFR (mL/Min/1.73m²) From Confirmatory Visit to 2 Years	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.
Long Term Safety: Mean Change in eGFR (mL/Min/1.73m²) From Confirmatory Visit to 5 Years	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.
Mean Change in Ambulatory Systolic Blood Pressure From Baseline to 6 Months	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.
Mean Change in Ambulatory Diastolic Blood Pressure From Baseline to 6 Months	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.
Mean Change in Office Diastolic Blood Pressure From Baseline to 6 Months	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.
Percentage of Participants Achieved Office Systolic Blood Pressure < 140 mmHg at 6 Months	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.
Mean Change in Office Systolic Blood Pressure From Baseline to 1 Year Post Denervation	Baseline to 1 year	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.
Mean Change in Office Systolic Blood Pressure From Baseline to 2 Years Post Denervation	Baseline to 2 years	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.
Mean Change in Office Systolic Blood Pressure From Baseline to 3 Years Post Denervation	Baseline to 3 years	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.
Mean Change in Office Systolic Blood Pressure From Baseline to 4 Years Post Denervation	Baseline to 4 years	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.
Mean Change in Office Systolic Blood Pressure From Baseline to 5 Years Post Denervation	Baseline to 5 years	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.
Mean Change in Office Diastolic Blood Pressure From Baseline to 1 Year Post Denervation	Baseline to 1 year	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.
Mean Change in Office Diastolic Blood Pressure From Baseline to 2 Years Post Denervation	Baseline to 2 years	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.
Mean Change in Office Diastolic Blood Pressure From Baseline to 3 Years Post Denervation	Baseline to 3 years	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.
Mean Change in Office Diastolic Blood Pressure From Baseline to 4 Years Post Denervation	Baseline to 4 years	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.
Mean Change in Office Diastolic Blood Pressure From Baseline to 5 Years Post Denervation	Baseline to 5 years	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.
Mean Change in Ambulatory Systolic Blood Pressure From Baseline to 1 Year Post Denervation	Baseline to 1 year	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.
Mean Change in Ambulatory Systolic Blood Pressure From Baseline to 2 Years Post Denervation	Baseline to 2 years	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.
Mean Change in Ambulatory Systolic Blood Pressure From Baseline to 3 Years Post Denervation	Baseline to 3 years	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.
Mean Change in Ambulatory Systolic Blood Pressure From Baseline to 4 Years Post Denervation	Baseline to 4 years	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.
Mean Change in Ambulatory Systolic Blood Pressure From Baseline to 5 Years Post Denervation	Baseline to 5 years	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.
Mean Change in Ambulatory Diastolic Blood Pressure From Baseline to 1 Year Post Denervation	Baseline to 1 year	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.
Mean Change in Ambulatory Diastolic Blood Pressure From Baseline to 2 Years Post Denervation	Baseline to 2 years	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.
Mean Change in Ambulatory Diastolic Blood Pressure From Baseline to 3 Years Post Denervation	Baseline to 3 years	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.
Mean Change in Ambulatory Diastolic Blood Pressure From Baseline to 4 Years Post Denervation	Baseline to 4 years	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.
Mean Change in Ambulatory Diastolic Blood Pressure From Baseline to 5 Years Post Denervation	Baseline to 5 years	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.

Trial Locations

Locations (33): Klinikum der Johannes-Gutenberg-Universitat
🇩🇪
Mainz, Germany
Fondazione Toscana Gabriele Monasterio CNR
🇮🇹
Massa, Tuscany, Italy
CHU de Besancon - Jean Minjoz
🇫🇷
Besancon, Franche-Comte, France
St-Etienne CHU
🇫🇷
St. Etienne, France
University of Athens, Ippocration Hospital
🇬🇷
Athens, Greece
Policlinico S.Orsola Malpighi
🇮🇹
Bologna, Italy
Institute Cardio. Paris-Sud-Institut Jacques Cartier
🇫🇷
Paris, Massy, France
Hopital Civil - Universitaires de Strasbourg
🇫🇷
Strasbourg, France
Hopital de la Croix Rousse
🇫🇷
Lyon, France
Klinikum Coburg GmbH
🇩🇪
Coburg, Bavaria, Germany
Centro Cardiologico Monzino
🇮🇹
Milano, Italy
Haga Ziekenhuis Locatie Leyenburg
🇳🇱
Den Haag, Netherlands
Klinikum Ingolstadt GmbH
🇩🇪
Ingolstadt, Bavaria, Germany
Kerckhoff-Klinik gGmbH
🇩🇪
Bad Nauheim, Hesse, Germany
Uni-Klinik Leipzig, Intervent. Angiologie
🇩🇪
Leipzig, Saxony, Germany
Universitatsklinikum Essen (AoR)
🇩🇪
Essen, Germany
Universitatsklinikum des Saarlandes
🇩🇪
Homburg, Germany
UMC Utrecht
🇳🇱
Utrecht, Netherlands
Dunedin Public Hospital
🇳🇿
Dunedin, New Zealand
Royal Melbourne Hospital - City Campus
🇦🇺
Parkville, Australia
Royal Perth Hospital
🇦🇺
Perth, Australia
Herz-und Diabetes Zentrum NRW
🇩🇪
Bad Oeynhausen, Nordrhein Westfalen, Germany
Jüdisches Krankenhaus Berlin
🇩🇪
Berlin, Germany
Universitats-Herzzentrum Freiburg - Bad Krozingen
🇩🇪
Bad Krozingen, Germany
Krankenhaus der Barmherzigen Bruder
🇩🇪
Trier, Germany
Hospital Universitario Donostia
🇪🇸
San Sebastián, Basque, Spain
St. Olavs University Hospital
🇳🇴
Trondheim, Norway
NIHR Barts Cardiovascular Biomedical Research Unit
🇬🇧
London, United Kingdom
Sahlgrenska University Hospital Gothenburg
🇸🇪
Goteborg, Sweden
Northern General Hospital
🇬🇧
Sheffield, United Kingdom
Royal Adelaide Hospital
🇦🇺
Adelaide, South Australia, Australia
The Prince Charles Hospital
🇦🇺
Chermside, Australia
Haukeland Universitetssykehus
🇳🇴
Bergen, Norway