Laparoscopic Adventitial Renal Denervation (RDN) for Refractory Hypertension

Официальное название

First-in-Man Clinical Study to Evaluate the Safety and Efficacy of Renal Artery Radiofrequency Ablation Clamp, Radiofrequency Ablation Generator for the Adjunctive Treatment of Refractory Hypertension and Drug-Intolerant Hypertension

Обзор

This is a first-in-human study to test the safety and effectiveness of a new device-based treatment for high blood pressure that is difficult to control with medicine. This condition is known as refractory hypertension. The study will enroll 10 adults aged 18 to 65 whose high blood pressure is not controlled even though they are taking three or more blood pressure medications. The treatment involves a new medical device called a Renal Artery Radiofrequency Ablation Clamp. This device is used during a keyhole (laparoscopic) surgery. It works by applying controlled heat (radiofrequency energy) to the outside of the arteries that supply blood to the kidneys. This procedure, known as renal denervation, aims to calm the nerves around these arteries that contribute to high blood pressure. Participants who join the study will first be monitored on a standard set of blood pressure medicines to confirm they are eligible. If they qualify, they will undergo the keyhole surgery. After the procedure, participants will be followed for 180 days (about 6 months) and will have several follow-up visits to check their blood pressure and overall health.

Подробное описание

Rationale: Hypertension is a leading risk factor for cardiovascular disease. A significant portion of patients have refractory hypertension, where blood pressure remains elevated despite the use of multiple antihypertensive medications. The renal sympathetic nervous system plays a crucial role in blood pressure regulation, and its overactivity is a key factor in hypertension. Renal Denervation (RDN) is a device-based therapy designed to lower blood pressure by ablating these nerves. While most existing RDN systems use an endovascular (inside the artery) approach, this method carries potential risks such as endothelial damage, thrombosis, or renal artery stenosis.

Study Objective and Design: This is a prospective, single-center, single-arm, first-in-man (FIM) clinical study designed to provide a preliminary evaluation of the safety and efficacy of a novel laparoscopic adventitial RDN system for treating refractory or drug-intolerant hypertension. A total of 10 subjects will be enrolled. The study aims to gather initial feasibility and safety data to support the design of future, larger clinical trials.

Intervention: The investigational procedure is a laparoscopic renal artery adventitial RDN. This technique involves placing a Renal Artery Radiofrequency Ablation Clamp around the external surface (adventitia) of the main renal arteries. A compatible radiofrequency generator delivers energy to the clamp's electrodes, creating targeted lesions to ablate the sympathetic nerves while preserving the integrity of the arterial wall.

Methodology: Potential subjects will be screened for eligibility. Qualified candidates will enter a 28-day run-in period where they will be treated with a standardized, fixed-dose combination of at least three antihypertensive drugs, including a diuretic. This period is to confirm refractory status and assess medication adherence, which is confirmed via urine analysis. Subjects who still meet the blood pressure criteria after the run-in period will undergo the laparoscopic RDN procedure. Post-procedure, subjects will be followed at discharge (or Day 7), Day 30, Day 90, and Day 180. Antihypertensive medications may be adjusted after 90 days according to a predefined protocol based on blood pressure response. Efficacy will be assessed by changes in office and 24-hour ambulatory blood pressure, as well as changes in medication burden. Safety will be monitored by tracking the incidence of Major Adverse Events (MAE), procedure-related complications, and changes in renal function throughout the 180-day follow-up period.

Вмешательства

• Устройство Renal Artery Radiofrequency Ablation Clamp
  This device is a clamp used during a laparoscopic surgical procedure. It is placed on the external surface (adventitia) of the renal artery and is connected to a radiofrequency generator. It delivers targeted radiofrequency energy to ablate the renal sympathetic nerves.

Первичные конечные точки

• Rate of Achieving Target Office Systolic Blood Pressure at 180 Days [Срок оценки: 180 days post-procedure]
• Change From Baseline in Antihypertensive Medication Composite Score at 180 Days [Срок оценки: 180 days post-procedure]

Вторичные конечные точки (4)

• Procedural Success Rate [Срок оценки: Intra-procedural]
• Change From Baseline in Mean 24-hour Ambulatory Systolic Blood Pressure at 180 Days [Срок оценки: Baseline and 180 days post-procedure]
• Incidence of Major Adverse Events (MAE) [Срок оценки: Up to 180 days post-procedure]
• Incidence of Laparoscopic Surgery-Related Adverse Events [Срок оценки: Up to 30 days post-procedure]

Критерии участия

Критерии включения

Age ≥18 years and ≤65 years, any sex.

Diagnosed with primary hypertension.

History of hypertension for at least 6 months.

Blood pressure meets the following two conditions:

Office systolic blood pressure ≥140mmHg and ≤180mmHg, and office diastolic blood pressure ≥90mmHg. If not taking a beta-blocker, resting heart rate must be ≥70bpm.

24-hour ambulatory blood pressure measurement shows an average systolic pressure ≥130mmHg or a daytime average systolic pressure ≥135mmHg.

Has a history of antihypertensive medication use within the last 6 months with uncontrolled blood pressure. Before enrollment, must undergo at least 28 days of a standardized medication regimen (including a diuretic and at least three drugs in total) with ≥80% compliance, while office SBP remains ≥140mmHg and ≤180mmHg, and office DBP remains ≥90mmHg.

Patient is willing and able to comply with follow-up requirements and has signed the informed consent form.

Критерии исключения

Secondary hypertension.

Target renal artery anatomy is unsuitable, including:

Renal artery diameter >9mm or <4mm.

Multiple renal arteries.

Severe calcification, stenosis >50%, malformation, fibromuscular dysplasia, or aneurysm in either renal artery.

History of renal artery intervention (e.g., balloon angioplasty or stenting).

Unsuitable for laparoscopic surgery via the retroperitoneal approach, including prior retroperitoneal surgery, retroperitoneal fibrosis, or severe obesity (BMI > 40 kg/m²).

History of kidney transplant or severe renal impairment (eGFR < 45 mL/min/1.73m²).

Hospitalization for a hypertensive crisis within the past year.

Severe liver dysfunction (ALT or AST > 3 times the upper limit of normal).

Type 1 diabetes.

History of a cardiovascular event (e.g., myocardial infarction, unstable angina) or cerebrovascular event (e.g., stroke, TIA) within the last 6 months.

Pregnancy or planning to become pregnant during the trial.

Participation in any other investigational drug or device trial within 3 months prior to screening.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fuwai Huazhong Cardiovascular Hospital — Чжэнчжоу

Публикации

• Gao C, Zhao L, Zhu L, Li M, Ding D, Liu Z, Fan Z, Zhang Y, Zhao W, Wang J. Laparoscopic-based perivascular unilateral renal sympathetic nerve denervation for treating resistant hypertension: a case report. Hypertens Res. 2019 Aug;42(8):1162-1165. doi: 10.1038/s41440-019-0237-3. Epub 2019 Feb 27. PMID 30814662
• Baik J, Song WH, Yim D, Lee S, Yang S, Lee HY, Choi EK, Jeong CW, Park SM. Laparoscopic Renal Denervation System for Treating Resistant Hypertension: Overcoming Limitations of Catheter-Based Approaches. IEEE Trans Biomed Eng. 2020 Dec;67(12):3425-3437. doi: 10.1109/TBME.2020.2987531. Epub 2020 Nov 19. PMID 32310758
• Liu Y, Zhu B, Zhu L, Zhao L, Ding D, Liu Z, Fan Z, Zhao Q, Zhang Y, Wang J, Gao C. Clinical outcomes of laparoscopic-based renal denervation plus adrenalectomy vs adrenalectomy alone for treating resistant hypertension caused by unilateral aldosterone-producing adenoma. J Clin Hypertens (Greenwich). 2020 Sep;22(9):1606-1615. doi: 10.1111/jch.13963. Epub 2020 Aug 18. PMID 32812324
• Zhao L, Su E, Yang X, Zhu B, Fan Z, Wang X, Qi D, Zhu L, Bai M, Zhang Y, Zhao Q, Li M, Gao C. Laparoscopic-based perivascular renal sympathetic nerve denervation: a feasibility study in a porcine model. Eur J Med Res. 2020 Jun 18;25(1):22. doi: 10.1186/s40001-020-00422-5. PMID 32552871
• Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, Kapelak B, Walton A, Sievert H, Thambar S, Abraham WT, Esler M. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009 Apr 11;373(9671):1275-81. doi: 10.1016/S0140-6736(09)60566-3. Epub 2009 Mar 28. PMID 19332353

Идентификаторы

NCT: NCT07108829 · HenanlCE202503

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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