Physiological Biomarker-Based Neural Dosing Study: A prospective, multicenter, single-arm study evaluating the clinical utility of biomarker-based neural dosing using evoked compound action potential (ECAP)-controlled closed-loop spinal cord stimulation (SCS).

The Evoke Spinal Cord Stimulator (SCS) System (Evoke System) is indicated as an aid in the management of chronic intractable pain of the trunk and/or limbs and will be used within its commercially approved indication. With the development of ECAP CL-SCS, this is the first time in SCS that true scientific inquiry into the neural dose that produces the clinical effect is available. With the Evoke System, objective measurement of therapy delivery through ECAPs allows for the reproducibility of the neural dose delivered in addition to individualization based on a patient’s unique spinal cord measurements. To understand the neurophysiological measurements (i.e., neural panel metrics) that correspond with the maximal analgesic effect (MAE) achieved with ECAP CL-SCS and provide guidelines for therapy delivery and adherence in future applications of CL-SCS, data from subjects with chronic back and leg pain (greater than or equal to 60mm on a Visual Analog Scale [VAS]) receiving CL-SCS in three studies of the Evoke System (Evoke randomized controlled trial [RCT] closed-loop arm [NCT02924129], ECAP [NCT04319887], and Durability [NCT04627974] were analyzed. The neural panel metrics included the following: System utilization: the proportion of time the system was on for the week prior to the visit. Percent time above ECAP threshold: the proportion of time a patient received stimulation above their individual ECAP threshold, out of the total stimulation time. ECAP dose: the median ECAP level (normalized ECAP amplitude [µV]). Dose ratio: the estimated current (mA) at the median ECAP level divided by the current (mA) at the ECAP threshold. Patients will be programmed to a dose ratio of 1.4x ECAP threshold. The spinal cord stimulator is implanted under the skin and is programmed by a device representative. The device representative delivers electrical impulses to the spinal cord and titrates the dose of stimulation up to a value of 40% above the point of neural activation. Patients are encouraged to run their stimulator at this precise dose. Patients are able to control their therapy with a remote control. Adherence will be monitored at each milestone visit. The neural panel metric measurements are clinical tools to be used by healthcare professionals. Healthcare professionals exercise their own clinical judgment based on the information provided to make decisions about treatment. The device will be programmed in accordance with the patients needs per the commercially available instructions for use. Individual patient spinal cord measurements and the patient’s subjective feedback should be considered when providing recommendations and titrating/tapering for each patient. The general guidelines for each individual patient’s therapy will be translated into the number of bars that should be illuminated for each applicable program on the patient’s remote control. This will be done to educate the patient on the therapy that produced the best clinical outcome in past patients when taking into account their own individual spinal cord measurements. The physician and patient will always have full control to modify treatment as needed for the individual’s therapy. The patient will always have full control of their system to turn on, off, or adjust their stimulation per the TGA approved labelling. Patients will be followed up at trial end, and 3, 6 and 12 months post permanent implant. Patients are encouraged to run their stimulator at the precise dose at all times, unless instructed by the technician (e.g. the patient only has pain during the daytime and will use the SCS during daytime hours). Patients will continue to use this precise dose of stimulation on their preferred program after the trial ends. The trial end refers to the end of the 12 month study duration.