Impact of Renal SympAthetic DenerVation on Chronic HypErtension
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 38
- 试验地点
- 2
- 主要终点
- Change in Ambulatory Diastolic Blood Pressure
研究概览
简要总结
Despite the development of many drug therapies designed to treat high blood pressure (hypertension), it remains a considerable and poorly managed health, social and economic burden. For various reasons, including the high health care costs of treatment, there are estimates that up to 65% of patients with high blood pressure have untreated and/or uncontrolled blood pressure (BP).
Aside from its effect on kidney function, chronic high blood pressure increases the risk for stroke, and heart disease. It is also thought to be involved in the formation of irregular heartbeats. This link between high blood pressure and heart health has been well described, as has their combined effect on the aging and the obesity-battling Western world.
A recently published study (Symplicity HTN-2 trial) established the benefit of a new treatment procedure, catheter-based renal sympathetic denervation (RSDN) for hypertension, as having enormous potential for the treatment of patients with high blood pressure. This multi-center trial will attempt to confirm and expand on these promising data. Patients who enroll in the trial will be followed for 4 years.
详细描述
Aside from its obvious impact on renal function, chronic hypertension significantly increases the risk for stroke, coronary artery disease, heart failure, and vascular disease, and it is believed to mediate the pathogenesis and progression of cardiac arrhythmias via its remodeling effects on cardiac anatomy. This inextricable link between hypertension and cardiovascular health has been well described, as has their combined effect on up to 40% of the aging, obesity-battling Western world.
Despite the development of numerous anti-hypertensive drug therapies-diuretics, angiotensin-converting enzyme inhibitors, alpha-adrenergic blockers, angiotensin-receptor blockers, calcium-channel blockers, beta blockers, and vasodilators-designed to block various and multiple avenues of the complex renal-cardiovascular circuit, hypertension remains a considerable, and poorly managed, social and economic burden. For various reasons, including the enormous health care costs of treatment, up to 65% of hypertensive patients have untreated and/or uncontrolled blood pressure (BP). Of those with uncontrolled blood pressure, ~10% have resistant hypertension-defined as elevated BP refractory to treatment with 3 antihypertensive agents of different classes.
But an even greater problem than the ineffectiveness of available therapies is their applicability. As has been observed with other illnesses, patients are often the greatest obstacles to their own care. Convincing patients to adhere to a life-long regimen of expensive medication for something which causes no immediate, palpable impact to their lives, is a challenging feat for today's pressed-for-time physician.
Therefore, of particular interest and profound promise is a recent study examining the effects on chronic blood pressure management of catheter-based renal sympathetic denervation (Symplicity HTN-1, Krum et al, Lancet 373:1275, 2009). This proof-of-principle study revealed that the procedure could be performed safely and without any procedure-related sequelae in 50 patients with baseline office blood pressure of 177±20 / 101±15, on 4.7 anti-hypertensive medications. At 12 months post-procedure, the mean reduction in office blood pressures was a remarkable -27/-17 mm Hg, with a concurrent 47% reduction in renal noradrenaline spillover. Importantly, these favorable blood pressure results were maintained over 2 years (see Fig).
Then, Esler et al performed a multicenter, randomized controlled trial comparing catheter based renal denervation to optimal medication therapy in patients with drug-resistant hypertension (Symplicity HTN-2, Lancet 2010; 376:1903-1909). In this study of 106 randomized patients, the 6-month office BPs in the denervation group decreased by 32/12 mmHg (SD 23/11, baseline of 178/96 mmHg, p<0.0001), whereas they did not differ from baseline in the control group (change of 1/0 mmHg [SD 21/10], baseline 178/97 mmHg, p=N.S.). There were no serious procedure-related or device-related complications. And most recently, besides the hydrostatic effect on blood pressure, it was recently demonstrated that RSDN significantly reduces LV mass and improves diastolic function in patients with refractory hypertension (J Am Coll Cardiol 2012; 59:901-9). Together, these favorable effects all suggest that there may important beneficial prognostic implications for RSDN in patients with resistant hypertension at high cardiovascular risk.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 18 and ≤ 85 years of age.
- •Refractory hypertension (per JNC-7, this is defined as BP ≥ 140/90 mmHg despite treatment with at least 3 anti-hypertensive drugs, at least one of which is a diuretic, or treatment by ≥ 4 anti-hypertensive drugs)
- •Stable anti-hypertensive drug regimen, where no modifications have occurred for at least 2 weeks.
- •Accessibility of renal vasculature.
- •Ability to understand the requirements of the study.
- •Willingness to adhere to study restrictions and comply with all post-procedural follow-up requirements.
排除标准
- •Subject has a known secondary cause of hypertension.
- •Subject has isolated White coat hypertension.
- •Subject has Type 1 Diabetes.
- •Subject has known significant renovascular abnormalities (e.g., significant renal artery stenosis, previous renal artery stenting or angioplasty that precludes the RSDN procedure because of no sites for ablation treatment, or the presence of an accessory renal artery in which the main renal artery is estimated to supply <75% of the kidney )
- •Significant renal artery stenosis is defined as > 50% diameter stenosis on renal angiography. Per the guidelines for noninvasive vascular laboratory testing: a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology, significant renal artery stenosis is defined by any one of the following criteria on renal duplex ultrasound; i) Renal artery to aorta peak systolic velocity ratio ≥ 3.5; ii) Peak Systolic Velocity > 200 cm/s with evidence of post-stenotic turbulence; iii) end diastolic velocity >150 cm/s ; iv) Resistive Index (RI) > 0.8; v) An occluded renal artery demonstrates no flow in the affected vessel.
- •Subject has hemodynamically significant valvular heart disease for which reduction of blood pressure would be considered hazardous.
- •Subject has New York Heart Association (NYHA) Class III or IV congestive heart failure, due to either systolic or diastolic dysfunction.
- •Subject has an eGFR<45 ml/min/1.73m2 (calculated by using the modified diet in renal disease (MDRD) formula), and is not receiving dialysis.
- •Subject has orthostatic hypotension. (per the American Academy of Neurology/American Autonomic Society Conesus Statement, this is defined as a sustained reduction of systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of 10 mm Hg within 3 min of standing or head-up tilt to at least 60° on a tilt table)
- •Subject has a life expectancy < 1 year for any medical condition.
- •Subject is currently enrolled in another investigational drug or device trial that would interfere with this study.
研究组 & 干预措施
Renal denervation group
Celcius Thermacool Catheter or Chilli II Cooled Ablation Catheter
干预措施: Celcius Thermacool Catheter or Chilli II Cooled Ablation Catheter (Device)
结局指标
主要结局
Change in Ambulatory Diastolic Blood Pressure
时间窗: baseline and 6 months
The change in diastolic blood pressure as measured by 24 hour ambulatory monitoring at 6 months as compared to from baseline.
Mean Change in Ambulatory Systolic Blood Pressure
时间窗: baseline and 6 months
The change in systolic blood pressure as measured by 24 hour ambulatory monitoring at 6 months as compared to from baseline.
次要结局
- Office Systolic BP(baseline, 6 month, 12 months)
- Office Diastolic BP(baseline, 6 month, 12 months)
- Renal Aortic Ratio(Baseline and 12 months)
- Blood Urea Nitrogen(baseline, 6 months, 12 months)
- Resistive Index(Baseline and 12 months)
- Renal Artery Dimensions(baseline and 12 months)
- Creatinine(baseline, 6 months, 12 months)
- Anti-hypertensive Medications(Baseline, 6 months, 12 months)
研究者
Vivek Reddy
Director Cardiac Arrhythmia Service, Professor Of Medicine
Icahn School of Medicine at Mount Sinai