Durability of Evoked Compound Action Potential (ECAP)-Controlled, Closed-Loop Spinal Cord Stimulation (SCS) in a Real-World European Chronic Pain Population

Abstract

Introduction: Closed-loop spinal cord stimulation (CL-SCS) is a recently introduced system that records evoked compound action potentials (ECAPs) from the spinal cord elicited by each stimulation pulse and uses this information to automatically adjust the stimulation strength in real time, known as ECAP-controlled SCS. This innovative system compensates for fluctuations in the distance between the epidural leads and the spinal cord by maintaining the neural response (ECAP) at a predetermined target level. This data collection study was designed to assess the performance of the first CL-SCS system in a real-world setting under normal conditions of use in multiple European centers. The study analyzes and presents clinical outcomes and electrophysiological and device data and compares these findings with those reported in earlier pre-market studies of the same system.

Methods: This prospective, multicenter, observational study was conducted in 13 European centers and aimed to gather electrophysiological and device data. The study focused on the real-world application of this system in treating chronic pain affecting the trunk and/or limbs, adhering to standard conditions of use. In addition to collecting and analyzing basic demographic information, the study presents data from the inaugural patient cohort permanently implanted at multiple European centers.

Results: A significant decrease in pain intensity was observed for overall back or leg pain scores (verbal numerical rating score [VNRS]) between baseline (mean ± standard error of the mean [SEM]; n = 135; 8.2 ± 0.1), 3 months (n = 93; 2.3 ± 0.2), 6 months (n = 82; 2.5 ± 0.3), and 12 months (n = 76; 2.5 ± 0.3). Comparison of overall pain relief (%) to the AVALON and EVOKE studies showed no significant differences at 3 and 12 months between the real-world data release (RWE; 71.3%; 69.6%) and the AVALON (71.2%; 73.6%) and EVOKE (78.1%; 76.7%) studies. Further investigation was undertaken to objectively characterize the physiological parameters of SCS therapy in this cohort using the metrics of percent time above ECAP threshold (%), dose ratio, and dose accuracy (µV), according to previously described methods. Results showed that a median of 90% (40.7-99.2) of stimuli were above the ECAP threshold, with a dose ratio of 1.3 (1.1-1.4) and dose accuracy of 4.4 µV (0.0-7.1), based on data from 236, 230, and 254 patients, respectively. Thus, across all three metrics, the majority of patients had objective therapy metrics corresponding to the highest levels of pain relief in previously reported studies (usage over threshold > 80%, dose ratio > 1.2, and error < 10 µV).

Conclusions: In conclusion, this study provides valuable insights into the real-world application of the ECAP-controlled CL-SCS system, highlighting its potential for maintaining effective pain relief and objective neurophysiological therapy metrics at levels seen in randomized control trials, and potential for quantifying patient burden associated with SCS system use via patient-device interaction metrics.

Clinical trial registration: In the Netherlands, the study is duly registered on the International Clinical Trials Registry Platform (Trial NL7889). In Germany, the study is duly registered as NCT05272137 and in the United Kingdom as ISCRTN27710516 and has been reviewed by the ethics committee in both countries.

Keywords: Chronic; Closed-loop; ECAP-controlled closed-loop; Electrophysiology; Evoked compound action potential; Neuropathic pain; Pain; Physiologic closed-loop control; Spinal cord stimulation.

Fig. 1

Patient-reported outcomes. A Mean (± SEM) baseline (n = 148) pain scores (VNRS) were 8.2 ± 0.1. After 12 months (n = 85), scores decreased to 2.6 ± 0.2. B Responder and high-responder rates. Vertical axis indicates responder/high-responder rates in %. Patients who showed exceptional pain relief were defined as high-responders (≥ 80.0%) and patients who responded with ≥ 50.0% pain relief were defined as responders. At 12 months, 76% of patients were responders and 41% high-responders. C Individual patient percentage change from baseline in overall pain scores at 12 months

Fig. 2

Patient-reported outcomes—stimulation-naïve patients. A Mean (± SEM) baseline (n = 135) overall pain scores (VNRS) in stimulation-naïve patients were 8.2 ± 0.1. After 12 months, (n = 76) pain scores decreased to 2.5 ± 0.3. B Responder and high-responder rates. At 12 months, 80% (n = 61 out of 76) of patients were responders, and 45% (n = 34 out of 76) of patients were high-responders. C Individual patient percentage change from baseline in overall pain scores at 12 months. D Comparison of overall pain relief (%) to the AVALON and EVOKE studies. No significant differences at 3 and 12 months between the real-world data release (RWE; 71.3%; 69.6%) and the AVALON (71.2%; 73.6%) and EVOKE (78.1%; 76.7%) studies

Fig. 3

Overview of prior neuromodulation experience and VNRS scores. A Sub-analysis of conversion patients (n = 13). Certain patients demonstrated prior use of multiple SCS devices. B Mean (± SEM) baseline (n = 13) overall pain scores (VNRS) for salvage/conversion patients were 7.9 ± 0.3. After 12 months (n = 9) pain scores decreased to 3.8 ± 0.5

Fig. 4

Patient-reported outcomes—patient satisfaction and sensation awareness to stimulation. A Subjects rated their satisfaction with the stimulator using a four-point scale (with options ranging from “very unsatisfied” to “very satisfied”) at the 3-month, 6-month, and 12-month follow-ups. At the 3-month follow-up (n = 96), more than 95% of the patients were very satisfied or satisfied with the therapy, which only improved at the 12-month follow-up (n = 85), where the percentage of very satisfied patients increased even more. B Subjects rated their sensation awareness of the stimulator using a five-point scale (with options ranging from “never aware of stimulation sensation” to “always aware of stimulation sensation”) at the 3-month, 6-month, and 12-month follow-ups. More than 60% of all patients (n = 95) at the 3-month follow-up were either always aware or usually aware of the stimulation sensation. This amount stayed more or less the same at the 6-month and 12-month follow-up visits

Fig. 5

In-clinic and out-of-clinic spinal cord activation. A Median (IQR: Q1–Q3) data at 12 months (n = 52) revealed the ECAP threshold to be 2.7 µV (− 3.2 to 7.8). Median data at 12 months (n = 52) revealed the ECAP amplitude at perception threshold to be 6.0 µV (2.0–14.0). The ECAP amplitude at the maximum discomfort level was 55.0 µV (38.0–82.5) at 12 months. The mode ECAP amplitude target, the patients’ actual activation outside the clinic, was at every time point greater than the median ECAP threshold at each visit interval at 12.0 µV (0.0–28–6) at 12 months.*If the activation plot was not analyzable due to technical issues or was not captured, the values were not taken into consideration. Therefore, not all patients have activation plot data presented here. B Patients used their patient controller to adjust stimulation or program once (median) every 3 days, i.e., 0.4 adjustments per day

Fig. 6

Neural metrics analysis. Scatterplots with associated distribution plots of usage over threshold, dose ratio, and dose accuracy