Efficacy and safety of renal denervation for Chinese patients with resistant hypertension using a microirrigated catheter: study design and protocol for a prospective multicentre randomised controlled trial

Abstract

IntroductionAvailable data show that approximately 8%–18% of patients with primary hypertension will develop resistant hypertension. In recent years, catheter-based renal denervation (RDN) has emerged as a potential treatment option for resistant hypertension. A number of observational studies and randomised controlled trials among non-Chinese patients have demonstrated its potential safety and efficacy.Methods and analysisThis is a multicentre, randomised, open-label, parallel-group, active controlled trial that will investigate the efficacy and safety of a 5F saline-irrigated radiofrequency ablation (RFA) used for RDN in the treatment of Chinese patients with resistant hypertension. A total of 254 patients who have failed pharmacological therapy will be enrolled. Eligible subjects will be randomised in a 1:1 ratio to undergo RDN using the RFA plus antihypertensive medication or to receive treatment with antihypertensive medication alone. The primary outcome measure is the change in 24 hours average ambulatory systolic blood pressure from baseline to 3 months, comparing the RDN-plus-medication group with the medication-alone group. Important secondary endpoints include the change in office blood pressure from baseline to 6 months after randomisation. Safety endpoints such as changes in renal function will also be evaluated. The full analysis set, according to the intent-to-treat principle, will be established as the primary analysis population.Ethics and disseminationAll participants will provide informed consent; the study protocol has been approved by the Independent Ethics Committee for each site. This study is designed to investigate the efficacy and safety of RDN using a 5F saline microirrigated RFA. Findings will be shared with participating hospitals, policymakers and the academic community to promote the clinical management of resistant hypertension in China.Trial registrationClinicalTrials.gov ID: NCT02900729; pre-results.

Hypertension in chronic kidney disease: What lies behind the scene

“…Reports have shown that the renalase knockout mouse is hypertensive and exquisitely sensitive to cardiac ischemia (Wu et al, 2010), and develops renal tubular damage that can be ameliorated with recombinant renalase treatment (Lee et al, 2013). The administration of recombinant renalase produces a powerful and rapid hypotensive effect on rats (Schiffrin et al, 2007;Wang et al, 2017) and reduces plasma NE, left ventricular hypertrophy (LVH), and cardiac fibrosis in 5/6 nephrectomy hypertensive CKD rats (Baraka and El Ghotny, 2012). Blood renalase levels are inversely correlated with GFR and are markedly reduced in ESRD patients (Desir, 2009).…”

“…The procedure itself ( Figure 2 ) involves the use of catheter-based devices that ablate the renal afferent and efferent (sympathetic) nerves surrounding the renal arteries using either radiofrequency, ultrasound energy, or trans-arterial injection of caustic substances ( Gajulapalli et al, 2020 ). Several trials have been conducted ( Krum et al, 2009 ; Investigators, 2010 ; Esler et al, 2012 ; Kandzari et al, 2012 ; Bakris et al, 2014 ; Bhatt et al, 2014 ; Liu et al, 2017 ; Sievert et al, 2017 ; Böhm et al, 2020 ), however to date, there is no global census or legislative approval of renal denervation as a clinical procedure for the treatment of hypertension non-pharmacologically. Although renal denervation has played an ameliorating role in reducing elevated BP and preserving renal function in diseased kidneys in humans ( Hering et al, 2012 ; Ott et al, 2015 ) and rats ( Yao et al, 2017 ) with CKD, other factors contributing to BP elevation remain, that are unalterable by renal denervation.…”