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
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Rate of Achieving Target Office Systolic Blood Pressure at 180 Days
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Rate of Achieving Target Office Systolic Blood Pressure at 180 Days
时间窗: 180 days post-procedure
The percentage of subjects whose office systolic blood pressure (SBP) is less than 140mmHg at the 180-day post-procedure follow-up. Office blood pressure will be measured in a resting state according to a standardized procedure.
Change From Baseline in Antihypertensive Medication Composite Score at 180 Days
时间窗: 180 days post-procedure
The change from baseline in a composite score reflecting the type and dose of antihypertensive medication required to achieve a target office SBP of \<140mmHg. The score is calculated as (number of drug classes) multiplied by (the sum of the doses), where a standard daily dose is defined as 1, a half dose is 0.5, and a double dose is 2. The change is calculated as the baseline score minus the 180-day score.
次要结局
- Procedural Success Rate(Intra-procedural)
- Change From Baseline in Mean 24-hour Ambulatory Systolic Blood Pressure at 180 Days(Baseline and 180 days post-procedure)
- Incidence of Major Adverse Events (MAE)(Up to 180 days post-procedure)
- Incidence of Laparoscopic Surgery-Related Adverse Events(Up to 30 days post-procedure)
研究者
Chuanyu Gao
Professor
Henan Institute of Cardiovascular Epidemiology