Effect of Renal Denervation on Stress, Hypertension and Anxiety Management (ERSHAM Study) in Patients With Uncontrolled Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- Anxiety 1
研究概览
简要总结
The ERSHAM (Effect of Renal Denervation on Stress, Hypertension and Anxiety Management) is a single-center, interventional, open-label, randomized controlled trial that will be conducted at the Hypertension Unit "ESH Excellence Center'', 1st Cardiology Department of the Medical School of the National and Kapodistrian University of Athens at the General Hospital of Athens "Hippokration", which is the reference center for uncontrolled hypertension and for sympathetic renal denervation (RDN) in our region. Sixty (60) consecutive patients aged 30-70 years with uncontrolled arterial hypertension either under anti-hypertensive treatment with 1 drug [at least 50% of maximum manufacturer's recommended dosage of an angiotensin-converting enzyme inhibitor (ACEI)/ angiotensin II receptor blocker (ARB) or a calcium channel blocker (CCB)] or naïve from antihypertensive treatment and HADS (Hospital anxiety and depression scale) anxiety subscore ≥ 8 will be enrolled (Figure 1). Patients will be randomized in a 1: 1 ratio to endovascular ultrasound RDN (Paradise renal denervation system, ReCor, CA, USA) (RDN) (n= 30) or to control group (n= 30). Baseline clinical data, cardiovascular risk factors, medical history as well as medication will be recorded in each group. After the randomization, patients who will be randomized to RDN group will undergo a computed tomography angiography (CTA) or magnetic resonance angiography (MRA) of the renal arteries in order to assess whether the renal arteries' anatomy is suitable for RDN by using the Paradise system. The images of the CTA/MRA will be uploaded onto BIOCLINICA web-based portal in order to optimize device use (RDN catheter) and location of ablations. Patients will not change their antihypertensive medications during the 3 months follow -up. After that, their management will be evaluated based on the current 2018 ESC/ESH guidelines.
Possible RDN-related adverse events will be recorded during the follow-up period. Blood pressure (BP) will be measured by office BP measurements as well as 24-hour ambulatory blood pressure monitoring. Anxiety and depression will be evaluated by the self-assessment hospital anxiety and depression scale (HADS). Stress management will be evaluated via Perceived Stress Scale-14 (PSS-14). To assess the quality of life (QoL) the health status questionnaire (SF-12) will be used. The social readjustment rating scale will be used in order to evaluate the probability of developing a stress-related disorder during the follow-up period. Finally, a questionnaire for personal stress due to high blood pressure will be applied at the baseline and at the end of the follow-up period.
Patients will be followed-up for 6 months after the randomization. A total of three (3) follow-up visits for each patient will be scheduled during the 6-month follow-up period of the study [1st (adverse events review), 3rd, and 6th month after the randomization). If there is a failure in reaching the office BP <140/90mmHg at the 3rd and 6th month, the antihypertensive therapy will be reevaluated according to the current ESH/ESC Guidelines.
All patients will give written informed consent and the study will be organized according to ethical considerations, as described in the Declaration of Helsinki for human medical studies, and the protocol will be approved by the institutional medical ethics committee.
详细描述
Background
Uncontrolled hypertension (HTN) is of multifactorial origin and continues to represent a major public health issue. Sympathetic renal denervation (RDN) has been proposed as a promising, minimally invasive method to contribute to the improvement of HTN control. Data from recent multicenter randomized studies (SPYRAL HTN-OFF MED, SPYRAL HTN-ON MED, RADIANCE-HTN SOLO) provided solid data that RDN could achieve a clinically meaningful ambulatory and office blood pressure (BP) reduction in hypertensive patients with and without antihypertensive medications by using different technologies (radiofrequency energy or ultrasound energy to ablate the renal fibers). Beyond the BP control, RDN has demonstrated pleiotropic effects that occur partly independent of the observed BP reduction in various clinical settings (decreasing the "burden" of arrhythmias, decreasing left ventricular hypertrophy, increasing aortic compliance, improving sleep apnea and metabolic profile ), while recent data showed a positive impact in psychological disorders.
It is well known that the autonomic nervous system (ANS) plays a dominant role in both HTN and psychological disorders. In particular, dysfunction of the autonomic nervous system is considered to be the pathophysiological link between hypertension, depression, and anxiety. Sympathetic stimulation through mechanisms, such as, for example, renin secretion, is associated with elevated BP, while stressful life events are associated with depression and anxiety either contributing to or initiating the HTN. It is therefore perceived that the limitation of sympathetic activation could have a significant effect on both the control of the HTN and the management of psychological comorbidities leading to an improved quality of life (QoL).
Although the co-existence of increased sympathetic tone, HTN, and psychological disorders is well-established in the literature, the data concerning the effect of sympathetic RDN on stress management, anxiety disorders, and depression in patients with HTN is rather limited and is based mainly on case series and in non-randomized studies. In fact, the available data come from a study, which showed that RDN reduces anxiety disorders and depression, while it improves the quality of life in patients with resistant hypertension. However, a number of limitations accompanied the study: the patients had difficult-to-control hypertension (resistant or refractory hypertension), and most of the patients received antihypertensive drugs that can influence the patients' mood such as b-blockers.
Innovation
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
- 30 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Consecutive patients aged 30-70 years with arterial hypertension diagnosed at least 3 months prior to the inclusion.
- •Office blood pressure (OBP) >140/90mmHg and <160/100 mmHg
- •Either no baseline hypertension treatment or hypertension treatment with one drug. The antihypertensive treatment will include a renin-angiotensin system (RAS) blocker [either an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB)] or a calcium channel blocker (CCB).
- •Unchanged antihypertensive therapy during the prior 8 weeks.
- •Patients with baseline anxiety subscore ≥ 8 according to the Hospital Anxiety and Depression Scale (HADS)
排除标准
- •Patients with secondary arterial hypertension or under treatment with b-blockers, diuretics, mineralocorticoid receptors antagonists (MRAs) or a centrally acting alpha-adrenergic agonist.
- •Patients under treatment with antidepressants and/or anxiolytic drugs.
- •Patients with a glomerular filtration rate (eGFR)] <45 ml / min / 1.73 m2 calculated using the CKD-EPI formula
- •Patients with evidence of any of the following criteria on either renal artery side:
- •Main renal artery diameter < 3.0 mm or > 8 mm
- •Main renal treatable artery length < 20 mm
- •Presence of renal artery stenosis of any origin ≥ 30%
- •Accessory arteries with diameter ≥ 2mm <3.0 mm
- •Calcification in renal arteries at location where energy is to be delivered
- •A single functioning kidney
- •Prior renal denervation procedure
- •Presence of abnormal kidney tumors
- •Renal artery with aneurysm
- •Pre-existing renal stent or history of renal artery angioplasty
- •Pre-existing aortic stent or history of aortic aneurysm
- •Fibromuscular disease of the renal arteries
- •Iliac/femoral artery stenosis precluding insertion of the Paradise Catheter
- •Patients with a history of acute coronary syndrome or stroke during the previous six months or Scheduled coronary interventional therapy during the next six months.
- •Patients with permanent atrial fibrillation, chronic heart failure and NYHA functional status II-IV, Cancer under therapy (radiotherapy, chemotherapy, immunotherapy)
- •Patients with life expectancy <1 year (at the time of inclusion).
- •Pregnant women or women who are planning to become pregnant.
- •Patients who do not provide written consent to participate in the study
研究组 & 干预措施
Control
The patient will not receive any interventional therapy
Renal Denervation Arm
Endovascular ultrasound renal denervation (Paradise renal denervation system, ReCor, CA, USA) (RDN)
干预措施: Endovascular ultrasound renal denervation (Paradise renal denervation system, ReCor, CA, USA) (RDN) (Procedure)
结局指标
主要结局
Anxiety 1
时间窗: From baseline (Screening Visit -1) at 3 months (Visit 2) of the follow-up period.
Change in the Hospital Anxiety and Depression Scale (HADS) anxiety subscore
Hypertension
时间窗: From baseline (Visit 0) at 3 months (Visit 2) of the follow-up period.
Change in the 24h systolic and diastolic blood pressure
次要结局
- Physical and Mental Health(From baseline (Visit 0) at 3 (Visit 2) and 6 months (Visit 3) of the follow-up period.)
- Office Blood Pressure 1(From baseline (Visit 0) at 3 months (Visit 2) of the follow-up period.)
- Ambulatory Blood Pressure Monitoring (ABPM)(From baseline (Visit 0) at 6 months (Visit 3).)
- Heart Rate(From baseline (Visit 0) at 3 (Visit 2) and 6 months (Visit 3) of the follow-up period.)
- Heart Rate Variability (HRV)(From baseline (Screening Visit -1) at 3 months (Visit 2) of the follow-up period)
- Office Blood Pressure 2(From baseline (Visit 0) at 6 months (Visit 3) of the follow-up period.)
- Apnea- Hypopnea(From baseline (Screening Visit -1) at 3 months (Visit 2) of the follow-up period.)
- Blood Pressure Variability (BPV)(From baseline (Screening Visit -1) at 3 months (Visit 2) of the follow-up period)
- Anxiety 2(From baseline (Screening Visit -1) at 6 months (Visit 3) of the follow-up period.)
- Depression(From baseline (Screening Visit -1) at 3 (Visit 2) and 6 months (Visit 3) of the follow-up period)
- Stress(From baseline (Visit 0) at 3 (Visit 2) and 6 months (Visit 3) of the follow-up period.)
- Hypertension(From baseline (Visit 0) at 3 months (Visit 2) of the follow-up period.)
研究者
Konstantinos Tsioufis
Professor of Cardiology
Hippocration General Hospital