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临床试验/NCT01673516
NCT01673516Unknown2 期

Effect of Renal Sympathetic Denervation on Resistant Hypertension and Cardiovascular Hemodynamic in Comparison to Intensive Medical Therapy Utilizing Impedance Cardiography

Oslo University Hospital2 个研究点 分布在 1 个国家目标入组 60 人开始时间: 2012年8月1日最近更新:
适应症
干预措施

试验速览

阶段
2 期
发起方
入组人数
60
试验地点
2
主要终点
Absolute change in office systolic blood pressure(SBP)

研究概览

简要总结

The purpose of this study is to demonstrate that Renal Sympathetic Denervation (RDN) improves the control of blood pressure (BP) in patients with treatment-resistant hypertension, as compared to intensive medical therapy (IMT) using hemodynamic parameters and then applying a predefined algorithm of drug selection (i.e. integrated hemodynamic management - IHM) during 6 months intensive treatment program (receiving antihypertensive care according to the 2007 ESH Guidelines). Working hypothesis: When it is possible to disrupt the sympatho-renal axis by RDN - BP reduction occurs to a greater extent and more rapidly than applying intensive medical therapy using IHM.

详细描述

Hypertension is the most common cardiovascular disease, affecting approximately 1 billion1 people worldwide. Hypertension is a major public health concern, because of its complications (coronary artery disease, heart failure, renal disease, stroke). Early blood pressure control in hypertensive patients guarantees the best prevention of cardiovascular events on the long term (2007 ESH-ESC Guidelines on the Management of Hypertension; VALUE study). However, in spite of education efforts and antihypertensive drugs, blood pressure control rates remain low. The most common cause of uncontrolled BP is inadequate pharmacological treatment, because the selection of antihypertensive agents is often done independently of the hemodynamic status of the patient (volemic status, peripheral resistance, cardiac inotropy).

The sympatho-renal axis describes the dual role of the kidney as originator of some central nervous system afferent signals and recipient of efferent sympathetic signals. Both the contribution of the kidney to central sympathetic drive and the consequences of sympathetic efferent drive to the kidney contribute to the development and sustenance of hypertension. Poly-pharmacy strategies for the treatment of elevated blood pressure have identified populations of patients with treatment resistant hypertension.

Treatment Resistant Hypertension(TRH) is a blood pressure that remains above goal in spite of the concomitant use of antihypertensive medications from more than 3 drug classes. Patients who require more than 4 drug classes to have their blood pressure controlled are also considered to have resistant hypertension. Preferably, the regimen should include a diuretic and all doses should be optimal2 .The true prevalence of treatment resistant hypertension is unknown. In clinical trials from 20 to 40% of randomized patients did not reach blood pressure targets3. In the National Health and Nutrition Examination Survey in USA (2003-2008), non-pregnant adults with hypertension were classified as resistant if their blood pressure was 140/90 mmHg or higher and if they reported using antihypertensive medications from 3 different drug classes or drugs from 4 antihypertensive drug classes regardless of blood pressure. The prevalence was 12.8% of the drug-treated hypertensive population. Risk factors for treatment-resistant hypertension include older age and obesity .

Treatment-resistant patients are more likely to have albuminuria, reduced renal function, and a history of diabetes mellitus, coronary heart disease, stroke or heart failure. They are at increased risk of cardiovascular complications although the true incidence of death and morbidity remains currently unknown.

In the Spanish Ambulatory Blood Pressure Monitoring Registry5, 8295 of 68045 treated patients (12.2%) had treatment resistant hypertension, defined as an office blood pressure equal to or exceeding 140 mm Hg systolic and/or 90 mm Hg diastolic.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
None

入排标准

年龄范围
18 Years 至 80 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Average SBP >140mmHg, measured per guidelines
  • 24 hour average ABPM daytime SBP >135mm/Hg
  • On stable medication regimen of full tolerated doses of 3 or more antihypertensive meds, with one being a diuretic
  • No changes for a minimum of 2 weeks prior to screening
  • No planned medication changes for 6 months
  • Age 18-80 years
  • At minimum, 3 antihypertensive medications must meet one or more of the following full dose criteria:
  • Highest labeled dose according to medication's labeling
  • Highest usual dose per clinical guidelines-JNC-7
  • Highest tolerated dose
  • Highest appropriate dose for the patient per the PI's clinical judgment

排除标准

  • Hemodynamically or anatomically significant renal artery abnormalities or stenosis >50% or prior renal artery intervention
  • eGFR < 45 mL/min/1.73m2 (MDRD formula)
  • Albumin/creatinine ratio > 50 mg/mmol
  • Type 1 diabetes mellitus
  • Known alcohol or drug abuse
  • Symptomatic orthostatic hypotension in past year
  • Stenotic valvular heart disease for which BP reduction would be hazardous
  • MI, unstable angina, or CVA in the prior 6 months
  • Known primary pulmonary HTN
  • Known pheochromocytoma, Cushing's disease, coarctation of the aorta, hyperthyroidism or hyperparathyroidism
  • Known primary hyperaldosteronism not adequately treated.

研究组 & 干预措施

group Co

Active Comparator

group Co receives intensive medical therapy utilizing integrated hemodynamic management calculated by impedance cardiography of "The HOTMAN® System"

干预措施: The HOTMAN® System (Device)

group RDN

Active Comparator

For patients who will be randomly assigned to undergo renal denervation by "The SymplicityTM Renal Denervation System", the femoral artery will be accessed with the standard endovascular technique and the catheter will be advanced into the renal artery and connected to a radiofrequency generator. As in Symplicity HTN 1 and 2 trials, four-to-six discrete, low-power radiofrequency ablations lasting up to 2 min each and of 8 watts or less to obtain up to four-six ablations separated both longitudinally and rotationally within each renal artery. During ablation, the catheter system monitored tip temperature and impedance, altering radiofrequency energy delivery in response to a predetermined algorithm.

干预措施: The SymplicityTM Renal Denervation System (Procedure)

结局指标

主要结局

Absolute change in office systolic blood pressure(SBP)

时间窗: at 6 months

is the absolute change in office SBP, after a 6 months follow-up.

次要结局

  • Short and long term safety of RDN as an interventional procedure(up to10 years)
  • Cost effectiveness(At 6 month and later)
  • Percentage of normalization of blood pressure(BP) at office, home and ABPM(at 6 months and later)
  • The normalization of hemodynamics.(at 6 month and later)

研究者

发起方
Oslo University Hospital
申办方类型
Other
责任方
Sponsor

研究点 (2)

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