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Renal denervation (RDN) continues to be evaluated as a therapy for hypertension and other sympathetically-driven morbidities. Most technologies under evaluation ablate periarterial nerves using energy delivered through the arterial wall. Chemical denervation using a neurolytic agent (alcohol) delivered directly to the perivascular space of the renal artery can be performed using the Peregrine System™ Infusion Catheter. The technique and mode of action of denervation using alcohol offers an alternative to energy-based approaches and is being assessed. Here we report on two studies.
The Peregrine System is an endovascular catheter with three micro-needles to deliver micro-volumes of a neurolytic agent as a single infusion to the perivascular space of each renal artery. Alcohol volumes from 0.15 to 0.6 mL have been successfully evaluated in preclinical models. Two clinical studies using similar protocols have been conducted in subjects with refractory hypertension using 0.3 mL alcohol per renal artery.
In both studies (28 subjects total) eGFR remained stable to slightly improve through 6 months. No adverse vascular events, as assessed by a core lab, were reported during the procedure or at 6 months. Procedures were performed with minimal to no sedation. Procedural results include: completed as intended 100%, procedure time per artery 9 ± 5 mins, procedural adverse events 5% (minor, transient back pain), fluoroscopy time 10 ± 12 mins, and contrast used 67 ± 25 mL. For the combined trials, office blood pressure at 6 months was reduced by 24 ± 17 mmHg. In the peregrine study, ABPM was reduced by 5 mmHg at 6-month and 7 mmHg at 1-year.
In these studies, it was possible to perform alcohol-mediated RDN. These studies show an early signal of effectiveness. A single-step infusion per artery, with the peregrine catheter, may minimize technical and operator variability. These studies were conducted before the implementation of new study designs for RDN, yet still provide a sound basis for further evaluation. An open label trial using 0.6 mL alcohol is on-going. A randomized, blinded sham-controlled, multinational trial incorporating recommended trial design is being finalized.