Hypertension, Vascular Diseases
Conditions
Keywords
denervation, resistant hypertension, essential hypertension
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).
Interventions
DEVICEThe Paradise® Renal Denervation Ultrasound System
Randomization will occur following the diagnostic renal angiogram. Blinded patients randomized to treatment will receive the renal denervation procedure using the Paradise System to deliver ultrasound energy to thermally ablate and disrupt the renal sympathetic nerves while sparing the renal arterial wall.
DEVICESham Procedure
Randomization will occur following the diagnostic renal angiogram. For blinded patients randomized to control, the diagnostic renal angiogram will be considered the sham procedure.
Sponsors
ReCor Medical, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Solo Cohort - Mean Difference in Average Daytime Ambulatory Systolic BP | from baseline to 2 months post procedure | Mean difference in average daytime ambulatory systolic BP of the Solo cohort |
| Trio Cohort - Median Change in Daytime Ambulatory Systolic BP | from baseline to 2 months post procedure | Median change in daytime ambulatory systolic BP of the Trio cohort |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in Average 24-hr/Night-time Ambulatory Systolic BP | from baseline to 2 months post procedure | — |
| Reduction in Average Daytime/24-hr/Night-time Diastolic BP | from baseline to 2 months post procedure | — |
| All-cause Mortality | from baseline to 36 months post-procedure | — |
| Hypertensive or Hypotensive Emergency Resulting in Hospitalization | up to 36 months | — |
| Hospitalization for Heart Failure | from baseline to 36 months post-procedure | — |
| Stroke, Transient Ischemic Attack, Cerebrovascular Accident | from baseline to 36 months post-procedure | — |
| Acute Myocardial Infarction | from baseline to 36 months post-procedure | — |
| End Stage Renal Disease | from baseline to 36 months post-procedure | — |
| Renal Artery or Vascular Complications Requiring Intervention | from baseline to 36 months post-procedure | — |
| Significant Embolic Events Resulting in End Organ Damage | from baseline to 1 month and 36 months post-procedure | — |
| Procedure Related Pain Lasting > 2 Days | from baseline to 1 month and 36 months post-procedure | — |
| Acute Renal Injury | from baseline to 1 month and 36 months post-procedure | — |
| Significant (>50%) and Severe (>75%) New Onset Renal Stenosis | from 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 Complications | from baseline to 1 month and 36 months post-procedure | — |
Countries
Belgium, France, Germany, Netherlands, Poland, United Kingdom, United States
Contacts
PRINCIPAL_INVESTIGATORMichel Azizi, MD, PhD
Hôpital Européen Georges-Pompidou
PRINCIPAL_INVESTIGATORAjay J Kirtane, M.D
Columbia University
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Solo Cohort - Renal Denervation 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 | 74 |
| Solo Cohort - Sham 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 | 72 |
| Trio Cohort - Renal Denervation Subjects with treatment resistant hypertension on a minimum of 3 antihypertensive medications will be included in the RADIANCE Trio cohort. | 69 |
| Trio Cohort - Sham Subjects with treatment resistant hypertension on a minimum of 3 antihypertensive medications will be included in the RADIANCE Trio cohort. | 67 |
| Total | 282 |
Baseline characteristics
| Characteristic | Solo Cohort - Renal Denervation | Solo Cohort - Sham | Trio Cohort - Renal Denervation | Trio Cohort - Sham | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 74 Participants | 72 Participants | 69 Participants | 67 Participants | 282 Participants |
| Age, Continuous | 54.4 years STANDARD_DEVIATION 10.2 | 53.8 years STANDARD_DEVIATION 10 | 52.3 years STANDARD_DEVIATION 7.5 | 52.8 years STANDARD_DEVIATION 9.1 | 53.32 years STANDARD_DEVIATION 9.2 |
| Race/Ethnicity, Customized Black | 12 Participants | 13 Participants | 14 Participants | 13 Participants | 52 Participants |
| Race/Ethnicity, Customized Other or unknown | 2 Participants | 7 Participants | 11 Participants | 4 Participants | 24 Participants |
| Race/Ethnicity, Customized White | 60 Participants | 52 Participants | 44 Participants | 50 Participants | 206 Participants |
| Sex: Female, Male Female | 28 Participants | 33 Participants | 13 Participants | 14 Participants | 88 Participants |
| Sex: Female, Male Male | 46 Participants | 39 Participants | 56 Participants | 53 Participants | 194 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 74 | 0 / 72 | 1 / 69 | 0 / 67 | 1 / 59 |
| other Total, other adverse events | 60 / 74 | 40 / 72 | 56 / 69 | 34 / 67 | 19 / 59 |
| serious Total, serious adverse events | 7 / 74 | 0 / 72 | 12 / 69 | 4 / 67 | 1 / 59 |
Outcome results
Primary
Solo Cohort - Mean Difference in Average Daytime Ambulatory Systolic BP
Mean difference in average daytime ambulatory systolic BP of the Solo cohort
Time frame: from baseline to 2 months post procedure
Population: Intention-to-treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Solo Cohort - Renal Denervation | Solo Cohort - Mean Difference in Average Daytime Ambulatory Systolic BP | -8.5 mm Hg | Standard Deviation 9.3 |
| Solo Cohort - Sham | Solo Cohort - Mean Difference in Average Daytime Ambulatory Systolic BP | -2.2 mm Hg | Standard Deviation 10 |
Primary
Trio Cohort - Median Change in Daytime Ambulatory Systolic BP
Median change in daytime ambulatory systolic BP of the Trio cohort
Time frame: from baseline to 2 months post procedure
Population: Intention-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Solo Cohort - Renal Denervation | Trio Cohort - Median Change in Daytime Ambulatory Systolic BP | -8 mm Hg |
| Solo Cohort - Sham | Trio Cohort - Median Change in Daytime Ambulatory Systolic BP | -3 mm Hg |
Secondary
Acute Myocardial Infarction
Time frame: from baseline to 36 months post-procedure
Secondary
Acute Renal Injury
Time frame: from baseline to 1 month and 36 months post-procedure
Secondary
All-cause Mortality
Time frame: from baseline to 36 months post-procedure
Secondary
End Stage Renal Disease
Time frame: from baseline to 36 months post-procedure
Secondary
Hospitalization for Heart Failure
Time frame: from baseline to 36 months post-procedure
Secondary
Hypertensive or Hypotensive Emergency Resulting in Hospitalization
Time frame: up to 36 months
Secondary
Major Access Site Complications
Time frame: from baseline to 1 month and 36 months post-procedure
Secondary
Procedure Related Pain Lasting > 2 Days
Time frame: from baseline to 1 month and 36 months post-procedure
Secondary
Reduction in Average 24-hr/Night-time Ambulatory Systolic BP
Time frame: from baseline to 2 months post procedure
Secondary
Reduction in Average Daytime/24-hr/Night-time Diastolic BP
Time frame: from baseline to 2 months post procedure
Secondary
Renal Artery or Vascular Complications Requiring Intervention
Time frame: from baseline to 36 months post-procedure
Secondary
Significant (>50%) and Severe (>75%) New Onset Renal Stenosis
as diagnosed by duplex ultrasound and confirmed by renal CTA/MRA or as diagnosed/confirmed by study defined renal CTA/MRA at 12 months
Time frame: from baseline to 6, 12, 24 and 36 months post-procedure
Secondary
Significant Embolic Events Resulting in End Organ Damage
Time frame: from baseline to 1 month and 36 months post-procedure
Secondary
Stroke, Transient Ischemic Attack, Cerebrovascular Accident
Time frame: from baseline to 36 months post-procedure