Uncontrolled Hypertension
Conditions
Keywords
Renal denervation (RDN), Radiofrequency renal denervation, Sympathetic nervous system, Interventional therapy, Interventional cardiology, Device-based therapy, Renal artery denervation, Blood pressure, Resistant Hypertension, Refractory Hypertension
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.
Interventions
Netrod™ renal denervation (RDN) system, which is indicated for the treatment of uncontrolled hypertension. It consists of the following two components: * Netrod™ Six-Electrode Basket Radiofrequency Renal Denervation Catheter and * Netrod™ Renal Denervation Radiofrequency Generator The catheter's electrodes deploy into a self-adaptive basket structure, optimizing contact with the vessel wall for effective ablation.
DEVICESham Procedure
Patients will be remained on the catheterization table for at least 20 min prior to sheath removal.
Sponsors
European Cardiovascular Research Center
Shanghai Golden Leaf MedTec Co. Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
Participants will be randomly assigned to either the RDN procedure, sham procedure, or open-label control (where patients do not receive any procedure and are off medication until primary endpoint measurement). After primary endpoint measurements at Month 3, patients in the sham and open-label control groups will have the option to receive the RDN procedure, referred to as crossover patients.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Subject with age ≥18 years or minimum age as required by local regulations and ≤80 years old at time of consent 2. 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 3. Subject or his/her legal representative must sign an IEC/REB-approved ICF for the study 4. Subject is willing to discontinue current antihypertensive medications at Screening V1 through the 3-month follow-up visit
Exclusion criteria
1. 1\. Subject who is pregnant, nursing or planning to become pregnant during the course of the study 2. 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) 3. Subject with single-kidney or history of kidney transplant 4. Subject with history of renal artery intervention (PTA or stenting) or RDN 5. 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. 6. Subject with known secondary hypertension 7. Subject with eGFR \<40 mL/min/l.73m² 8. Subject with history of hospitalization for hypertensive emergency within past year 9. Subject with type I diabetes mellitus 10. Subject with primary pulmonary hypertension 11. Subject with history of bleeding diathesis and haematological disorders or coagulopathy 12. Subject with recent history of any embolism within 6 months 13. Subject with history of coronary artery intervention, unstable angina or myocardial infarction 14. Subject with stable angina and therefore treated anti-anginal medication (betablockers, calcium antagonists, long-acting nitrates) 15. Subject with history of abdominal aortic aneurysm 16. Subject with atrial fibrillation or history of atrial fibrillation in the last 3 years or on rhythm control medication for arrhythmia 17. Subject with a history of ventricular fibrillation or ventricular tachycardia 18. Subject known with serum HIV-positive 19. Subject who is allergic to contrast agents and not responding to preventive medication 20. Subject with acute or severe systemic infections 21. Subject with mental illness or any psychological problems that may interfere with participating in the study 22. Subject with history of stroke or transient ischemic attack (TIA) 23. Subject with malignant tumors or end-stage disease 24. Subject with severe PAD along the access path to renal arteries, including abdominal aneurysm 25. Subject with severe heart valve stenosis or regurgitation 26. Subject with heart failure requiring medications (i.e. ACE/ARB, SGTL2i, diuretics). 27. Subject with uncontrolled hyperthyroidism or hypothyroidism 28. 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 29. Subject who requires mechanical ventilation other than CPAP for sleep apnea 30. Subject with a implanted pacemaker or ICD/CRT device 31. Subject with a history of major surgery or trauma within 30 days prior to enrolment 32. Subject who has planned surgery or cardiovascular intervention within the next 12 months 33. Subject who is participating in other drug or medical device clinical investigations 34. Subject who has known drug or alcohol dependence, difficulty to understand the clinical investigation protocol, inability/unwillingness to follow the clinical investigation protocol 35. Subject who is unsuitable to participate in this study in the opinion of investigators 36. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean daytime ambulatory systolic blood pressure | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 BP (SBP) within the target range (SBP \<140 mmHg) at 3-month post procedure for all enrolled subjects, and 12-, 24- and 36-month post procedure for the subjects who underwent RDN |
| 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 office systolic blood pressure (SBP) within the target range (SBP \<130 mmHg) at 3-month post procedure for all enrolled subjects, and 12-, 24- and 36-month post procedure for the subjects who underwent RDN |
| 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 | Percentage of patients with mean ambulatory systolic blood pressure (ASBP) within the target range (SBP \<130 mmHg) at 3-month post procedure for all enrolled subjects, and 12-, 24- and 36-month post procedure for the subjects who underwent RDN |
| Office blood pressure (BP) and home BP | From baseline at Screening Visit 2 to Month 1, 3, 12, 24 and 36 post-procedure | Changes from baseline in office blood pressure (BP) and home BP at 1- and 3-month post procedure for all enrolled subjects, and 12-, 24- and 36-month post procedure for the subjects who underwent RDN |
| Safety event rates | At Month 3 post-procedure | The following safety event rates to 3-month post procedure for all enrolled subjects, and the following event rates at 12-, 24- and 36-month post procedure for the subjects who underwent RDN procedure: * All-cause mortality * End-stage renal disease (ESRD) defined as stage 5 CKD (eGFR \< 15 mL/min/l.73m²) * ≥50% decline in eGFR or \>50% increase in serum creatinine from baseline * New myocardial infarction or acute coronary syndrome (ACS) * New stroke or CVA * Renal artery reintervention * New renal artery stenosis \> 70% confirmed by angiography * Hospitalization for hypertensive crisis not related to confirmed non-adherence of antihypertensive medications * Hospitalization for major cardiovascular- or hemodynamic-related events (such as heart failure or atrial fibrillation) |
| Device deficiency rates | At Visit 4, day 0 (procedure) | Device deficiency rates |
| Quality of life changes | From baseline at Screening Visit 2 to Month 3, 12, 24 and 36 post-procedure | Quality of life changes at 12 months and annually through 3 years post index procedure |
| The proportion of ambulatory SBP decreased by 5 and 10 mmHg | At Month 3 post-procedure | The proportion of ambulatory SBP decreased by 5 and 10 mmHg at 3-month 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 | Changes from baseline in mean ambulatory BP including 24-hour ASBP and ADBP, daytime and nighttime SBP and DBP measured by 24-hour ABPM at 1-, 3-month for all enrolled subjects, and 12-, 24- and 36-month for the subjects who underwent RDN. |
Countries
Switzerland
Outcome results
None listed