Clinical trial NCT06722651: EuroNetrod HTN OFF-Med Study of Renal Denervation with NetrodTM Six-electrode Radiofrequency RDN System
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Uncontrolled Hypertension
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
Lead sponsor: Shanghai Golden Leaf MedTec Co. Ltd
Sponsor class: INDUSTRY
Collaborators: name: European Cardiovascular Research Center
First posted: 2024-12-09
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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."
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean daytime ambulatory systolic blood pressure
timeFrame: From baseline at Screening Visit 2 to Month 3 post-procedure
measure: Periprocedural major adverse event (MAE) rate
timeFrame: At 30 days post-procedure
Secondary outcomes:
measure: Office blood pressure (BP) and home BP
timeFrame: From baseline at Screening Visit 2 to Month 1, 3, 12, 24 and 36 post-procedure
measure: Mean ambulatory BP including 24-hour ASBP and ADBP, daytime and nighttime SBP and DBP
timeFrame: From baseline at Screening Visit 2 to Month 1, 3, 12, 24 and 36 post-procedure
measure: Percentage of patients with office systolic BP (SBP) within the target range (SBP <140 mmHg)
timeFrame: At Month 3, 12, 24 and 36 post-procedure
measure: Percentage of patients with office systolic blood pressure (SBP) within the target range (SBP <130 mmHg)
timeFrame: At Month 3, 12, 24 and 36 post-procedure
measure: Percentage of patients with mean ambulatory systolic blood pressure (ASBP) within the target range (SBP <130 mmHg)
timeFrame: At Month 3, 12, 24 and 36 post-procedure
measure: The proportion of ambulatory SBP decreased by 5 and 10 mmHg
timeFrame: At Month 3 post-procedure
measure: Safety event rates
timeFrame: At Month 3 post-procedure
measure: Device deficiency rates
timeFrame: At Visit 4, day 0 (procedure)
measure: Quality of life changes
timeFrame: From baseline at Screening Visit 2 to Month 3, 12, 24 and 36 post-procedure
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
state: Basel-Stadt
Study officials:
affiliation: Department of Cardiology, University Hospital Basel
name: Felix Mahfoud, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Mater Misericordiae University Hospital
name: Andrew Sharp, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li Y, Gao F, Ren C, Ma G, Bu P, Fu G, Chen H, Han Z, Li Y, Li J, Ma X, Hao L, Chen Y, Chen M, Chen X, Liu X, Jiang J, Yu J, Li N, Ma X, Yang B, Cong H, Wang X, Fan Q, Lv S, Wu D, Dai Q, Qiu F, Cai H, Zhou YJ. The Netrod six-electrode radiofrequency renal denervation system for uncontrolled hypertension: a sham-controlled trial. Eur Heart J. 2024 Nov 21;45(44):4761-4764. doi: 10.1093/eurheartj/ehae703. No abstract available.