Randomized Controlled Clinical Study to Evaluate the Novel Netrod™ Renal Denervation System and the Impact of Sham vs Open-Label Control in European Patients With Uncontrolled Primary Hypertension in the Absence of Hypertensive Medication
Trial Snapshot
- Phase
- Not Applicable
- Status
- Withdrawn
- Sponsor
- Enrollment
- 260
- Locations
- 2
- Primary Endpoint
- Mean daytime ambulatory systolic blood pressure
Study Overview
Brief Summary
This randomized controlled investigation aims to evaluate the efficacy and safety of the Netrod™ RDN system in patients with uncontrolled primary hypertension in the absence of antihypertensive medication, comparing the outcomes between renal denervation, sham procedure, and open-label control groups.
Detailed Description
This is a prospective, multi-center, blinded, three-arm randomized controlled study to demonstrate the effectiveness and safety of the Netrod™ RDN system for treating treating patients with uncontrolled primary hypertension in the absence of antihypertensive medications. This clinical investigation will enroll 260 patients in Europe. Patients with uncontrolled primary hypertension (office BP ≥150/90 mmHg and <180/110 mmHg) who are willing to discontinue antihypertensive medications will be screened after providing informed consent.
All eligible patients will undergo a medication washout period of at least three weeks, and those who continue to meet the eligibility requirements will be randomized in a 2:1:1 ratio to one of three groups: renal denervation (RDN), a sham procedure (renal artery angiogram only), or an open-label group (not undergoing the renal angiogram).
All subjects randomized to either the treatment or sham procedure groups will be evaluated at hospital discharge. All subjects will be evaluated at 1 and 3 months post-procedure. Additionally, patients who undergo the RDN procedure will also be evaluated at 12, 24, and 36 months post-procedure. All subjects will remain off antihypertensive medications until the primary endpoint is assessed at the 3-month follow-up visit, after which antihypertensive medications may be reintroduced.
Patients in the RDN and sham-control groups, as well as all clinical follow-up assessors, will be blinded to the treatment allocation. The primary efficacy endpoint is the change in daytime ambulatory systolic blood pressure (ASBP) from baseline at three months post-procedure. The primary safety endpoint is the periprocedural major adverse event (MAE) rate at 30 days post-procedure.
Subjects enrolled in the sham and open-label control groups may cross over to RDN at three months. Those who cross over will restart the follow-up schedule post-RDN procedure.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subject with age ≥18 years or minimum age as required by local regulations and ≤80 years old at time of consent
- •Subject with hypertension who has an office BP of ≥150/90 mmHg and <180/110 mmHg (meet both SBP and DBP criteria) at screening V3 and mean daytime ASBP ≥140 mmHg and <170 mmHg by 24-hour ABPM at Screening V3
- •Subject or his/her legal representative must sign an IEC/REB-approved ICF for the study
- •Subject is willing to discontinue current antihypertensive medications at Screening V1 through the 3-month follow-up visit
Exclusion Criteria
- •Subject who is pregnant, nursing or planning to become pregnant during the course of the study
- •Subject with unilateral or bilateral renal artery that are not suitable for ablation procedure (renal artery stenosis more than 50%, renal aneurysm, renal artery abnormality, renal artery diameter <3 mm or treatable segment length <20 mm)
- •Subject with single-kidney or history of kidney transplant
- •Subject with history of renal artery intervention (PTA or stenting) or RDN
- •Subject with any conditions that may affect the accuracy of blood pressure measurement: such as the diameter of the upper arm is too large for the cuff, or arrhythmia, etc.
- •Subject with known secondary hypertension
- •Subject with eGFR <40 mL/min/l.73m²
- •Subject with history of hospitalization for hypertensive emergency within past year
- •Subject with type I diabetes mellitus
- •Subject with primary pulmonary hypertension
- •Subject with history of bleeding diathesis and haematological disorders or coagulopathy
- •Subject with recent history of any embolism within 6 months
- •Subject with history of coronary artery intervention, unstable angina or myocardial infarction
- •Subject with stable angina and therefore treated anti-anginal medication (betablockers, calcium antagonists, long-acting nitrates)
- •Subject with history of abdominal aortic aneurysm
- •Subject with atrial fibrillation or history of atrial fibrillation in the last 3 years or on rhythm control medication for arrhythmia
- •Subject with a history of ventricular fibrillation or ventricular tachycardia
- •Subject known with serum HIV-positive
- •Subject who is allergic to contrast agents and not responding to preventive medication
- •Subject with acute or severe systemic infections
- •Subject with mental illness or any psychological problems that may interfere with participating in the study
- •Subject with history of stroke or transient ischemic attack (TIA)
- •Subject with malignant tumors or end-stage disease
- •Subject with severe PAD along the access path to renal arteries, including abdominal aneurysm
- •Subject with severe heart valve stenosis or regurgitation
- •Subject with heart failure requiring medications (i.e. ACE/ARB, SGTL2i, diuretics).
- •Subject with uncontrolled hyperthyroidism or hypothyroidism
- •Subject with severe electrolyte abnormalities, defined as values above and below the limits of normal (ULN) on repeated measurements despite normalization efforts, or with liver function abnormalities, defined as 2 > ULN
- •Subject who requires mechanical ventilation other than CPAP for sleep apnea
- •Subject with a implanted pacemaker or ICD/CRT device
- •Subject with a history of major surgery or trauma within 30 days prior to enrolment
- •Subject who has planned surgery or cardiovascular intervention within the next 12 months
- •Subject who is participating in other drug or medical device clinical investigations
- •Subject who has known drug or alcohol dependence, difficulty to understand the clinical investigation protocol, inability/unwillingness to follow the clinical investigation protocol
- •Subject who is unsuitable to participate in this study in the opinion of investigators
- •Subjects who are incapacitated or unable to provide informed consent due to cognitive impairment, mental illness, or other conditions that affect their decision-making capacity.
Outcomes
Primary Outcomes
Mean daytime ambulatory systolic blood pressure
Time Frame: From baseline at Screening Visit 2 to Month 3 post-procedure
Between-group difference in baseline adjusted change in mean daytime ambulatory systolic blood pressure (ASBP) at 3 months compared to baseline measured by 24 hours ambulatory blood pressure monitoring (ABPM) (RDN vs sham vs open-label).
Periprocedural major adverse event (MAE) rate
Time Frame: At 30 days post-procedure
Periprocedural major adverse event (MAE) rate, defined as a composite of the following events at 30 days post procedure: * All-cause mortality * End-stage renal disease (ESRD) defined as stage 5 CKD (eGFR \< 15 mL/min/l.73m²) or hemodialysis * Significant embolic event resulting in end-organ damage * Renal artery perforation or dissection requiring intervention * Major vascular complications requiring medical or surgical intervention * Hospitalization for hypertensive crisis (unless clearly demonstrated to be associated with non-adherence with antihypertensive medications in the subjects on escape medication) * New renal artery stenosis \> 70% (must be confirmed by angiography)
Secondary Outcomes
- Office blood pressure (BP) and home BP(From baseline at Screening Visit 2 to Month 1, 3, 12, 24 and 36 post-procedure)
- Mean ambulatory BP including 24-hour ASBP and ADBP, daytime and nighttime SBP and DBP(From baseline at Screening Visit 2 to Month 1, 3, 12, 24 and 36 post-procedure)
- Percentage of patients with office systolic BP (SBP) within the target range (SBP <140 mmHg)(At Month 3, 12, 24 and 36 post-procedure)
- Percentage of patients with office systolic blood pressure (SBP) within the target range (SBP <130 mmHg)(At Month 3, 12, 24 and 36 post-procedure)
- Percentage of patients with mean ambulatory systolic blood pressure (ASBP) within the target range (SBP <130 mmHg)(At Month 3, 12, 24 and 36 post-procedure)
- The proportion of ambulatory SBP decreased by 5 and 10 mmHg(At Month 3 post-procedure)
- Safety event rates(At Month 3 post-procedure)
- Device deficiency rates(At Visit 4, day 0 (procedure))
- Quality of life changes(From baseline at Screening Visit 2 to Month 3, 12, 24 and 36 post-procedure)