Clinical trial NCT02649426: A Study of the ReCor Medical Paradise System in Clinical Hypertension
Official title: The "RADIANCE-HTN" Study. A Study of the ReCor Medical Paradise System in Clinical Hypertension
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Hypertension
Vascular Diseases
Keywords: denervation
resistant hypertension
essential hypertension
Lead sponsor: ReCor Medical, Inc.
Sponsor class: INDUSTRY
First posted: 2016-01-07
Enrollment: 282
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RADIANCE-HTN is a randomized, double-blind, sham controlled, 2-cohort study (TRIO and SOLO) designed to demonstrate efficacy and document the safety of the Paradise Renal Denervation System in two distinct populations of hypertensive subjects.

Detailed description: Subjects with essential hypertension controlled on 1 or 2 antihypertensive medications or uncontrolled on 0-2 antihypertensive medications will be included in the RADIANCE Solo cohort while subjects with treatment resistant hypertension on a minimum of 3 antihypertensive medications will be included in the RADIANCE Trio cohort. Prior to randomization, subjects will be hypertensive in the absence of hypertension medication (SOLO) or despite the presence of a stabilized, single pill, triple, fixed dose antihypertensive medication regimen (TRIO).

Eligibility criteria: TRIO and SOLO Inclusion Criteria:

* Appropriately signed and dated informed consent
* Age ≥18 and ≤75 years at time of consent
* Documented history of essential hypertension
* SOLO Cohort only: Either an average seated office BP \< 180/110 mmHg at screening visit while on a stable regimen of 1 or 2 antihypertensive medications for at least 4 weeks prior to consent or an average seated office BP ≥ 140/90 mmHg \<180/110 mmHg despite lifestyle measures on no antihypertensive medications
* TRIO Cohort only: Average seated office BP ≥ 140/90 mmHg at screening visit while on a stable regimen of at least 3 antihypertensive medications of different classes including a diuretic for at least 4 weeks prior to consent
* Documented daytime ABP ≥ 135/85 mmHg and \< 170/105 mmHg after 4-week washout/run-in period (SOLO cohort) or after 4-week stabilization period (TRIO cohort)
* Suitable renal anatomy compatible with the renal denervation procedure and documented by renal CTA or MRA of good quality performed within one year prior to consent (a CTA or MRA will be obtained in patients without a recent (≤1 year) renal imaging)
* Able and willing to comply with all study procedures

Solo Exclusion Criteria:

* Renal artery anatomy on either side, ineligible for treatment including:

  * Main renal artery diameter \< 4 mm and \> 8 mm
  * Main renal artery length \< 25 mm
  * A single functioning kidney
  * Presence of abnormal kidney (or secreting adrenal) tumors
  * Renal artery with aneurysm
  * Pre-existing renal stent or history of renal artery angioplasty
  * Prior renal denervation procedure
  * Fibromuscular disease of the renal arteries
  * Presence of renal artery stenosis of any origin ≥ 30%
  * Accessory arteries with diameter ≥ 2mm \<4 mm and \> 8 mm\*
* Evidence of active infection within 7 days of procedure
* Iliac/femoral artery stenosis precluding insertion of the Paradise Catheter
* Type I diabetes mellitus or uncontrolled Type II diabetes (defined as a plasma Hb1Ac ≥ 9.0%)
* Documented history of chronic active inflammatory bowel disorders such as Chrohn's disease or ulcerative colitis
* eGFR of \<40 mL/min/1.73 m2 (by Modification of Diet in Renal Disease formula)
* Brachial circumference ≥ 42 cm
* Any history of cerebrovascular event (e.g. stroke, transient ischemic event, cerebrovascular accident)
* Any history of severe cardiovascular event (myocardial infarction, CABG, acute heart failure requiring hospitalization (NYHA III-IV)
* Documented confirmed episode(s) of stable or unstable angina
* Documented repeat (\>1) hospitalization for hypertensive crisis within the prior 12 months
* Prescribed to any standard antihypertensive of cardiovascular medication (e.g. beta blockers) for other chronic conditions (e.g. ischemic heart disease) such that discontinuation might pose serious risk to health
* Documented history of persistent or permanent atrial tachyarrhythmia
* Active implantable medical device (e.g. ICD or CRT-D; neuromodulator/spinal stimulator; baroreflex stimulator)
* Chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnea.
* Primary pulmonary hypertension
* Documented contraindication or allergy to contrast medium not amenable to treatment
* Limited life expectancy of \< 1 year at the discretion of the Investigator
* Any known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or for any reason in the opinion of the investigator, would be unlikely or unable to comply with study protocol requirements or whose participation may result in data analysis confounders (e.g. night shift workers)
* Pregnant, nursing or planning to become pregnant (negative pregnancy test required, documented within a maximum of 7 days prior to procedure for all women of child bearing potential. Documentation of effective contraception is also required for women of child bearing potential) Concurrent enrollment in any other investigational drug or device trial (participation in non-interventional Registries is acceptable)

TRIO Exclusion Criteria

* Renal artery anatomy on either side, ineligible for treatment including:

  * Main renal artery diameter \< 3.5 mm and \> 8 mm
  * Main renal artery length \< 20 mm
  * A single functioning kidney
  * Presence of abnormal kidney tumors
  * Renal artery with aneurysm
  * Pre-existing renal stent or history of renal artery angioplasty
  * Pre-existing aortic stent or history of aortic aneurysm
  * Prior renal denervation procedure
  * Fibromuscular disease of the renal arteries
  * Presence of renal artery stenosis of any origin ≥ 30%
  * Accessory arteries with diameter ≥2 mm \<3.5 mm and \> 8 mm\*
* Iliac/femoral artery stenosis precluding insertion of the Paradise Catheter
* Evidence of active infection within 7 days of procedure
* Secondary hypertension not including sleep apnea (documented through clinical work up within the 12 months prior to consent- see protocol body for details)
* Type I diabetes mellitus or uncontrolled Type II diabetes (defined as a plasma Hb1Ac ≥ 9.0%)
* Documented history of chronic active inflammatory bowel disorders such as Crohn's disease or ulcerative colitis
* eGFR of \<40 mL/min/1.73 m2 (by Modification of Diet in Renal Disease formula)
* Brachial circumference ≥ 42 cm
* Any history of cerebrovascular event (e.g. stroke, transient ischemic event, cerebrovascular accident) within 3 months prior to consent
* Any history of severe cardiovascular event (e.g. myocardial infarction, CABG, acute heart failure requiring hospitalization (NYHA III-IV) within 3 months prior to consent
* Documented repeat (\>1) hospitalization for hypertensive crisis within the prior 3 months
* Documented confirmed episode(s) of unstable angina within 3 months prior to consent
* Documented intolerance or contraindication for any of the antihypertensive drugs prescribed as a requirement of the study protocol
* Prescribed to any standard anti-hypertensive CV medication (other than beta blockers) for other chronic conditions (e.g. ischemic heart disease) such that discontinuation might pose serious risk to health
* Documented history of persistent or permanent atrial tachyarrhythmia
* Active implantable medical device (e.g. ICD or CRT-D; neuromodulator/spinal stimulator; baroreflex stimulator)
* Chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnea.
* Primary pulmonary hypertension
* Documented contraindication or allergy to contrast medium not amenable to treatment
* Limited life expectancy of \< 1 year at the discretion of the Investigator
* Night shift workers
* Any known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or for any reason in the opinion of the investigator, would be unlikely or unable to comply with study protocol requirements or whose participation may result in data analysis confounders
* Pregnant, nursing or planning to become pregnant (documented negative pregnancy test required documented within a maximum of 7 days prior to procedure for all women of child bearing potential. Documentation of effective contraception is also required for women of child bearing potential)
* Concurrent enrollment in any other investigational drug or device trial (participation in non-interventional Registries is acceptable)

Primary outcomes:
measure: Solo Cohort - Mean Difference in Average Daytime Ambulatory Systolic BP
timeFrame: from baseline to 2 months post procedure
measure: Trio Cohort - Median Change in Daytime Ambulatory Systolic BP
timeFrame: from baseline to 2 months post procedure
Secondary outcomes:
measure: Reduction in Average 24-hr/Night-time Ambulatory Systolic BP
timeFrame: from baseline to 2 months post procedure
measure: Reduction in Average Daytime/24-hr/Night-time Diastolic BP
timeFrame: from baseline to 2 months post procedure
measure: All-cause Mortality
timeFrame: from baseline to 36 months post-procedure
measure: Hypertensive or Hypotensive Emergency Resulting in Hospitalization
timeFrame: up to 36 months
measure: Hospitalization for Heart Failure
timeFrame: from baseline to 36 months post-procedure
measure: Stroke, Transient Ischemic Attack, Cerebrovascular Accident
timeFrame: from baseline to 36 months post-procedure
measure: Acute Myocardial Infarction
timeFrame: from baseline to 36 months post-procedure
measure: End Stage Renal Disease
timeFrame: from baseline to 36 months post-procedure
measure: Renal Artery or Vascular Complications Requiring Intervention
timeFrame: from baseline to 36 months post-procedure
measure: Significant Embolic Events Resulting in End Organ Damage
timeFrame: from baseline to 1 month and 36 months post-procedure
measure: Procedure Related Pain Lasting > 2 Days
timeFrame: from baseline to 1 month and 36 months post-procedure
measure: Acute Renal Injury
timeFrame: from baseline to 1 month and 36 months post-procedure
measure: Significant (>50%) and Severe (>75%) New Onset Renal Stenosis
timeFrame: from baseline to 6, 12, 24 and 36 months post-procedure
measure: Major Access Site Complications
timeFrame: from baseline to 1 month and 36 months post-procedure
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: Sutter Health Medical Center
state: California
city: Stamford
country: United States
facility: Stamford Hospital
state: Connecticut
city: Gainesville
country: United States
facility: The Cardiac and Vascular Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Springfield
country: United States
facility: Southern Illinois University Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Franciscan Health Indianapolis
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Heart and Vascular Insitute
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: The Brigham and Women's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Reno
country: United States
facility: Renown Institute for Heart& Vascular Health
state: Nevada
city: Browns Mills
country: United States
facility: Deborah Heart and Lung Center
state: New Jersey
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University / NewYork Presbyterian Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Plano
country: United States
facility: The Heart Hospital Baylor Plano
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Brussels
country: Belgium
facility: Cliniques Universitaires St Luc
city: Bordeaux
country: France
facility: Hôpital Saint-André - CHU Bordeaux
city: Lille
country: France
facility: CHRU Lille - Institut Coeur Poumon
city: Lyon
country: France
facility: Hôpital de la Croix Rousse
city: Paris
country: France
facility: Hôpital Européen Georges-Pompidou
city: Toulouse
country: France
facility: Clinique Pasteur
city: Dusseldorf
country: Germany
facility: University Clinic Dusseldorf
city: Erlangen
country: Germany
facility: University Clinic Erlangen
city: Freiburg
country: Germany
facility: Universitäts-Herzzentrum Freiburg-Bad Krozingen GmbH
city: Homburg
country: Germany
facility: University Clinic of Saarland
city: Leipzig
country: Germany
facility: Leipzig Heart Center
city: Lübeck
country: Germany
facility: Sana Kliniken Lübeck GmbH
city: Mainz
country: Germany
facility: Katholisches Klinikum Mainz
city: Maastricht
country: Netherlands
facility: Maastricht University Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Gdańsk
country: Poland
facility: Medical University of Gdansk
city: Warsaw
country: Poland
facility: Institute of Cardiology
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: England
city: London
country: United Kingdom
facility: Imperial College London, Hammersmith Hospital
state: England
city: Basildon
country: United Kingdom
facility: The Essex Cardiothoracic Centre - Basildon & Thurrock University Hospitals
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital (Wonford)
city: Hastings
country: United Kingdom
facility: Conquest Hospital - Hastings
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
Study officials:
affiliation: Hôpital Européen Georges-Pompidou
name: Michel Azizi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Ajay J Kirtane, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Azizi M, Mahfoud F, Weber MA, Sharp ASP, Schmieder RE, Lurz P, Lobo MD, Fisher NDL, Daemen J, Bloch MJ, Basile J, Sanghvi K, Saxena M, Gosse P, Jenkins JS, Levy T, Persu A, Kably B, Claude L, Reeve-Stoffer H, McClure C, Kirtane AJ; RADIANCE-HTN Investigators. Effects of Renal Denervation vs Sham in Resistant Hypertension After Medication Escalation: Prespecified Analysis at 6 Months of the RADIANCE-HTN TRIO Randomized Clinical Trial. JAMA Cardiol. 2022 Dec 1;7(12):1244-1252. doi: 10.1001/jamacardio.2022.3904.
citation: Sanghvi K, Wang Y, Daemen J, Mathur A, Jain A, Dohad S, Sapoval M, Azizi M, Mahfoud F, Lurz P, Sayer J, Levy T, Zagoria R, Loening AM, Coleman L, Craig D, Horesh-Bar M, Kirtane AJ. Renal Artery Variations in Patients With Mild-to-Moderate Hypertension From the RADIANCE-HTN SOLO Trial. Cardiovasc Revasc Med. 2022 Jun;39:58-65. doi: 10.1016/j.carrev.2021.09.008. Epub 2021 Sep 30.
citation: Fisher NDL, Kirtane AJ, Daemen J, Rader F, Lobo MD, Saxena M, Abraham J, Schmieder RE, Sharp ASP, Gosse P, Claude L, Song Y, Azizi M; RADIANCE-HTN Investigators. Plasma renin and aldosterone concentrations related to endovascular ultrasound renal denervation in the RADIANCE-HTN SOLO trial. J Hypertens. 2022 Feb 1;40(2):221-228. doi: 10.1097/HJH.0000000000002994.
citation: Azizi M, Sanghvi K, Saxena M, Gosse P, Reilly JP, Levy T, Rump LC, Persu A, Basile J, Bloch MJ, Daemen J, Lobo MD, Mahfoud F, Schmieder RE, Sharp ASP, Weber MA, Sapoval M, Fong P, Pathak A, Lantelme P, Hsi D, Bangalore S, Witkowski A, Weil J, Kably B, Barman NC, Reeve-Stoffer H, Coleman L, McClure CK, Kirtane AJ; RADIANCE-HTN investigators. Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial. Lancet. 2021 Jun 26;397(10293):2476-2486. doi: 10.1016/S0140-6736(21)00788-1. Epub 2021 May 16.
citation: Gosse P, Cremer A, Kirtane AJ, Lobo MD, Saxena M, Daemen J, Wang Y, Stegbauer J, Weber MA, Abraham J, Kario K, Bangalore S, Claude L, Liu Y, Azizi M. Ambulatory Blood Pressure Monitoring to Predict Response to Renal Denervation: A Post Hoc Analysis of the RADIANCE-HTN SOLO Study. Hypertension. 2021 Feb;77(2):529-536. doi: 10.1161/HYPERTENSIONAHA.120.16292. Epub 2020 Dec 28.
citation: Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Lobo MD, Sharp ASP, Bloch MJ, Basile J, Wang Y, Saxena M, Lurz P, Rader F, Sayer J, Fisher NDL, Fouassier D, Barman NC, Reeve-Stoffer H, McClure C, Kirtane AJ; RADIANCE-HTN Investigators. Six-Month Results of Treatment-Blinded Medication Titration for Hypertension Control After Randomization to Endovascular Ultrasound Renal Denervation or a Sham Procedure in the RADIANCE-HTN SOLO Trial. Circulation. 2019 May 28;139(22):2542-2553. doi: 10.1161/CIRCULATIONAHA.119.040451. Epub 2019 Mar 17.
citation: Calhoun DA, Schiffrin EL, Flack JM. Resistant Hypertension: An Update. Am J Hypertens. 2019 Jan 1;32(1):1-3. doi: 10.1093/ajh/hpy156. No abstract available.
citation: Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Davies J, Basile J, Kirtane AJ, Wang Y, Lobo MD, Saxena M, Feyz L, Rader F, Lurz P, Sayer J, Sapoval M, Levy T, Sanghvi K, Abraham J, Sharp ASP, Fisher NDL, Bloch MJ, Reeve-Stoffer H, Coleman L, Mullin C, Mauri L; RADIANCE-HTN Investigators. Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial. Lancet. 2018 Jun 9;391(10137):2335-2345. doi: 10.1016/S0140-6736(18)31082-1. Epub 2018 May 23.