The objective of the RADIANCE II Pivotal study is to demonstrate the effectiveness and safety of the Paradise System in subjects with Stage 2 hypertension on 0-2 medications at the time of consent. Prior to randomization, subjects will be…
ID
Source
Brief title
Condition
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The Primary Efficacy endpoint is a reduction in average daytime ambulatory
systolic BP from baseline to 2 months post procedure.
Secondary outcome
The statistical analysis of the Secondary Efficacy Endpoints will follow the
methodology of the Primary Efficacy Endpoint:
• Reduction in average 24-hr ambulatory systolic BP at 2 months post procedure.
• Reduction in average office systolic BP at 2 months post procedure
• Reduction in average home systolic BP at 2 months post procedure
• Reduction in average daytime ambulatory diastolic BP at 2 months post
procedure
• Reduction in average 24-hr ambulatory diastolic BP at 2 months post procedure
• Reduction in average office diastolic BP at 2 months post procedure
• Reduction in average home diastolic BP at 2 months post procedure
The primary safety endpoint is the 30 day post randomization incidence of Major
Adverse Events (MAE), a patient level composite of the incidence of the
following events:
• All-cause mortality
• New onset (acute) end-stage renal disease (eGFR< 15 mL/min/m2 or need for
renal replacement therapy)
• Significant embolic event resulting in end-organ damage (e.g., kidney/bowel
infarct, lower extremity ulceration or gangrene, or doubling of serum
• creatinine)
• Renal artery perforation requiring an invasive intervention
• Renal artery dissection requiring an invasive intervention
• Major vascular complications (e.g, clinically significant groin hematoma,
arteriovenous fistula, pseudoaneurysm) requiring surgical repair, interventional
procedure, thrombin injection, or blood transfusion (requiring more than 2
units of packed red blood cells within any 24-hr period during the first 7 days
post randomization)
• Hospitalization for hypertensive or hypotensive crisis
• Hospitalization for major cardiovascular- or hemodynamic- related events
(e.g. HF; MI; Stroke)
• New onset Stroke
• New onset Myocardial Infarction
or,
• New renal artery stenosis >70%, confirmed by angiography within 6 months of
randomization
Background summary
The ReCor Medical Paradise® Renal Denervation System (Paradise System) is a
catheter-based system that delivers ultrasound energy to thermally ablate and
disrupt the renal efferent and afferent sympathetic nerves while sparing the
renal arterial wall. The goal of renal nerve ablation is to achieve a reduction
in sympathetic over-activity with the resultant effect of reducing systemic
arterial blood pressure (BP), and mitigating resultant end organ damage.
Study objective
The objective of the RADIANCE II Pivotal study is to demonstrate the
effectiveness and safety of the Paradise System in subjects with Stage 2
hypertension on 0-2 medications at the time of consent. Prior to randomization,
subjects will be hypertensive in the absence of hypertension medication
Study design
RADIANCE II is a randomized, double-blind, sham-controlled, single cohort study
designed to demonstrate the effectiveness and safety of the Paradise Renal
Denervation System in hypertensive subjects.
Intervention
Subjects with hypertension (average seated office BP >= 140/90 mmHg and <
180/120 mmHg will undergo a 4-week washout period of drug discontinuation. Drug
discontinuation will occur in accordance with accepted, institutional
guidelines for the subjects* current medication. Subjects currently not taking
any antihypertensive medication with an average seated office BP >= 140/90 mmHg
and < 180/120 mmHg will undergo a 4-week run-in period.
After 4 weeks of drug discontinuation or run-in, all subjects will undergo a
second office BP check. Assuming that the subject has not met the safety escape
criteria during the washout/run-in period, they will undergo a 24-hr ambulatory
BP (ABP) measurement. Subjects whose daytime ABP remains >= 135/85 mmHg and
<170/105 mmHg, will undergo a baseline renal Computed Tomography Angiography
(CTA) or Magnetic Resonance Angiography (MRA) to rule out renal abnormalities,
renal artery pathology and/or significant renal artery stenosis, and to confirm
anatomical eligibility if a cross-sectional imaging study (either CTA or MRA)
is not already available that has been performed within one year prior to
consent. Subjects with suitable renal artery anatomy on CTA/MRA will undergo a
renal angiogram procedure. Subjects whose renal anatomy is re-confirmed as
suitable will then be randomized to renal denervation or blinded control
(*sham*).*
*For those subjects randomized to blinded control, the renal angiogram will be
considered the sham
procedure
Study burden and risks
Since all subjects that are included in the RADIANCE-HTN Study have been
diagnosed with hypertension, all patients may benefit from the close evaluation
of their hypertension via frequent office follow-ups, medication review and
home and 24-hr ambulatory blood pressure measurements. All subjects may also
benefit from having diagnostic non-invasive and invasive evaluation of their
renal anatomy in the event of previously undiagnosed renal abnormalities or
stenosis. These benefits may help to balance any additional burden caused by
having to come monthly to the hospital for the purpose of the study for the
first 6 months.
The renal denervation procedure is a standard interventional cardiology
procedure that can be performed quickly with minimal injury to non-target
tissues. Ablation of nerves can be painful however the procedure is tolerable
with appropriate analgesic medication. For patients that are treated, there is
a potential that they may have their elevated blood pressure decreased without
the need for additional antihypertensive medications or indeed with a
concomitant reduction in antihypertensive medications. Over the long term, such
a reduction in blood pressure may result in a decreased risk of cardiovascular
events including stroke, that are associated with prolonged hypertension. The
procedure risks are limited to short-term pain, and standard angioplasty
catheter related risks. For sham patients, the risks related to the procedure
are limited to those related to a renal angiogram procedure which can be
reduced further by appropriate use of appropriate guide catheters,
anticoagulation protocols taking into consideration the risk to the patient and
analgesia.
Before treatment:
Questions about healthcare
Questions about possible changes in medication intake
2x office bloodpressure
24-hour ambulatory BP
2X physical examination
12-lead ECG
withdrawal HTN medication
blood and urine samples
urine analysis for detection of blood pressure medications
CTA/MRA (if needed)
Pregnancy test (if applicable)
During procedure day: sedation and pain relief medication per hospital
protocol, catheterization, angiogram, renal denervation both kidneys
Discharge; Blood pressure measurement (if required), Questions about possible
changes in medication intake, pain perception, blinding index
Visits and procedures during study (na 1, 2, 3, 4, 5, 6 en 12) months
• BP measurement
• Review and discuss home BP measurements
• Physical examinations
• Questions about healthcare
• Questions about possible changes in medication intake
Additional assessments done during visits at 2, 6 en 12 months:
* 24-hour ambulatory BP
* ECG
* Blood and urine samples
* Urine analysis for detection of blood pressure medications
* Questions about healthcare
* Questions about possible changes in medication intake
* Questions about patient idea whether is treated or not (not at 12 months)
* CTA / MRA after 6 and 12 months (at 12 months, only for the renal denervation
group)
Visits and procedures during study after 24, 36, 48 en 60 months:
* BP measurement
* Physical examinations
* Questions about healthcare
There are possible risks associated with the general renal denervation
procedure as well as risks specifically associated with use of the Paradise
catheter system. These include but are not limited to:
Pain
Arrhythmias (bradycardia or tachycardia)
Cardiopulmonary arrest
Embolism
Allergy to contrast
Renal insufficiency/renal failure
Hematoma/pseudo aneurysm
Hypertension or hypotension
Infection
Fever
Renal artery stenosis/dissection/perforation/spasm
Nephrectomy
Arterio-venous or enteric fistula
Hematuria
Exposure to radiation
Cerebrovascular events including Stroke and TIA
There are also potential risks associated with the use of antihypertensive
medication including allergy or intolerance.
Dr.Molewaterplein 40
Rotterdam 3015 GD
NL
Dr.Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
• Appropriately signed and dated informed consent
• Documented history of hypertension
• Previously or currently prescribed antihypertensive therapy
• Average seated office BP >= 140/90 mmHg <180/120 mmHg at Screening Visit (V0)
while stable for at least 4 weeks on 0-2 anti-hypertensive medications of
different classes
• Able and willing to comply with all study procedures
Subjects who meet the following criteria will be considered eligible for
randomization:
• Documented daytime ABP >= 135/85 mmHg and < 170/105 mmHg at Baseline Visit
(V1) after 4-week washout/run-in period
• Suitable renal anatomy compatible with the renal denervation procedure,
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) cross-sectional renal imaging) and confirmed by renal angiogram in
subjects that continue to procedure
Exclusion criteria
• Renal artery anatomy on either side, ineligible for treatment including:
o Main renal artery diameter < 3 mm or > 8 mm
o Main renal treatable artery length < 20 mm (may include proximal branching)
o A single functioning kidney
o Presence of abnormal kidney tumors
o Renal artery with aneurysm
o Pre-existing renal stent or history of renal artery angioplasty
o Pre-existing aortic stent or history of aortic aneurysm
o Prior renal denervation procedure
o Fibromuscular disease of the renal arteries
o Presence of renal artery stenosis of any origin >= 30%
o Accessory arteries with diameter >=2mm <3.5 mm or > 8 mm
• Known, uncorrected causes of secondary hypertension other than sleep apnea
• Any history of cerebrovascular event (e.g. stroke, transient ischemic event,
cerebrovascular accident)
• Any history of severe cardiovascular event (e.g. 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 and/or any hospitalization for hypertensive crisis within three
(3) months prior to consent
• 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 in the opinion of
the Investigator
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT03614260 |
| CCMO | NL67166.078.19 |