A Study of the ReCor Medical Paradise System in Clinical Hypertension

The "RADIANCE-HTN" Study. A Study of the ReCor Medical Paradise System in Clinical Hypertension

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.

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).

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)