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A Study of the ReCor Medical Paradise System in Clinical Hypertension

Not Applicable
Active, not recruiting
Conditions
Vascular Diseases
Hypertension
Interventions
Device: The Paradise® Renal Denervation Ultrasound System
Device: Sham Procedure
Registration Number
NCT02649426
Lead Sponsor
ReCor Medical, Inc.
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).

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
282
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Ultrasound Renal DenervationThe Paradise® Renal Denervation Ultrasound SystemSubjects in the TRIO or SOLO cohorts that are randomized to treatment, will receive renal denervation following a renal angiogram
Sham ProcedureSham ProcedureFor subjects in TRIO or SOLO cohorts that randomize to the sham procedure, the diagnostic renal angiogram intervention will be considered the sham procedure.
Primary Outcome Measures
NameTimeMethod
Trio Cohort - Median Change in Daytime Ambulatory Systolic BPfrom baseline to 2 months post procedure

Median change in daytime ambulatory systolic BP of the Trio cohort

Solo Cohort - Mean Difference in Average Daytime Ambulatory Systolic BPfrom baseline to 2 months post procedure

Mean difference in average daytime ambulatory systolic BP of the Solo cohort

Secondary Outcome Measures
NameTimeMethod
Reduction in Average 24-hr/Night-time Ambulatory Systolic BPfrom baseline to 2 months post procedure
Hypertensive or Hypotensive Emergency Resulting in Hospitalizationup to 36 months
Hospitalization for Heart Failurefrom baseline to 36 months post-procedure
Acute Myocardial Infarctionfrom baseline to 36 months post-procedure
Renal Artery or Vascular Complications Requiring Interventionfrom baseline to 36 months post-procedure
Acute Renal Injuryfrom baseline to 1 month and 36 months post-procedure
Stroke, Transient Ischemic Attack, Cerebrovascular Accidentfrom baseline to 36 months post-procedure
Reduction in Average Daytime/24-hr/Night-time Diastolic BPfrom baseline to 2 months post procedure
Significant (>50%) and Severe (>75%) New Onset Renal Stenosisfrom baseline to 6, 12, 24 and 36 months post-procedure

as diagnosed by duplex ultrasound and confirmed by renal CTA/MRA or as diagnosed/confirmed by study defined renal CTA/MRA at 12 months

Major Access Site Complicationsfrom baseline to 1 month and 36 months post-procedure
All-cause Mortalityfrom baseline to 36 months post-procedure
End Stage Renal Diseasefrom baseline to 36 months post-procedure
Significant Embolic Events Resulting in End Organ Damagefrom baseline to 1 month and 36 months post-procedure
Procedure Related Pain Lasting > 2 Daysfrom baseline to 1 month and 36 months post-procedure

Trial Locations

Locations (49)

Cedars-Sinai Medical Center

🇺🇸

Los Angeles, California, United States

Emory University Hospital Midtown

🇺🇸

Atlanta, Georgia, United States

Stamford Hospital

🇺🇸

Stamford, Connecticut, United States

The Cardiac and Vascular Institute

🇺🇸

Gainesville, Florida, United States

Southern Illinois University Medicine

🇺🇸

Springfield, Illinois, United States

Renown Institute for Heart& Vascular Health

🇺🇸

Reno, Nevada, United States

Deborah Heart and Lung Center

🇺🇸

Browns Mills, New Jersey, United States

New York University School of Medicine

🇺🇸

New York, New York, United States

Columbia University / NewYork Presbyterian Hospital

🇺🇸

New York, New York, United States

University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Hôpital Saint-André - CHU Bordeaux

🇫🇷

Bordeaux, France

CHRU Lille - Institut Coeur Poumon

🇫🇷

Lille, France

Clinique Pasteur

🇫🇷

Toulouse, France

Universitäts-Herzzentrum Freiburg-Bad Krozingen GmbH

🇩🇪

Freiburg, Germany

Katholisches Klinikum Mainz

🇩🇪

Mainz, Germany

Maastricht University Hospital

🇳🇱

Maastricht, Netherlands

Medical University of Gdansk

🇵🇱

Gdańsk, Poland

Royal Devon and Exeter Hospital (Wonford)

🇬🇧

Exeter, United Kingdom

The Essex Cardiothoracic Centre - Basildon & Thurrock University Hospitals

🇬🇧

Basildon, United Kingdom

Conquest Hospital - Hastings

🇬🇧

Hastings, United Kingdom

St Bartholomew's Hospital

🇬🇧

London, United Kingdom

Nottingham University Hospitals NHS Trust

🇬🇧

Nottingham, United Kingdom

The Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

University Hospitals Cleveland Medical Center

🇺🇸

Cleveland, Ohio, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Erasmus Medical Center

🇳🇱

Rotterdam, Netherlands

Minneapolis Heart Institute

🇺🇸

Minneapolis, Minnesota, United States

Franciscan Health Indianapolis

🇺🇸

Indianapolis, Indiana, United States

Vanderbilt University

🇺🇸

Nashville, Tennessee, United States

University of Utah

🇺🇸

Salt Lake City, Utah, United States

Imperial College London, Hammersmith Hospital

🇬🇧

London, England, United Kingdom

Royal Bournemouth Hospital

🇬🇧

Bournemouth, England, United Kingdom

Cliniques Universitaires St Luc

🇧🇪

Brussels, Belgium

Hôpital Européen Georges-Pompidou

🇫🇷

Paris, France

Hôpital de la Croix Rousse

🇫🇷

Lyon, France

University Clinic of Saarland

🇩🇪

Homburg, Germany

University Clinic Dusseldorf

🇩🇪

Dusseldorf, Germany

University Clinic Erlangen

🇩🇪

Erlangen, Germany

Leipzig Heart Center

🇩🇪

Leipzig, Germany

Sana Kliniken Lübeck GmbH

🇩🇪

Lübeck, Germany

The Heart Hospital Baylor Plano

🇺🇸

Plano, Texas, United States

Institute of Cardiology

🇵🇱

Warsaw, Poland

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Ochsner Heart and Vascular Insitute

🇺🇸

New Orleans, Louisiana, United States

Sutter Health Medical Center

🇺🇸

Sacramento, California, United States

University of North Carolina at Chapel Hill School of Medicine

🇺🇸

Chapel Hill, North Carolina, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

University Medical Center Utrecht

🇳🇱

Utrecht, Netherlands

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