ECAP-controlled closed-loop versus open-loop SCS for the treatment of chronic pain: 36-month results of the EVOKE blinded randomized clinical trial
Authors: Mekhail Nagy A , Levy Robert M , Deer Timothy R , Kapural Leonardo , Li Sean , Amirdelfan Kasra , Pope Jason E , Hunter Corey W , Rosen Steven M , Costandi Shrif J , Falowski Steven M , Burgher Abram H , Gilmore Christopher A , Qureshi Farooq A , Staats Peter S , Scowcroft James , McJunkin Tory , Carlson Jonathan , Kim Christopher K , Yang Michael I , Stauss Thomas , Petersen Erika A , Hagedorn Jonathan M , Rauck Richard , Kallewaard Jan W , Baranidharan Ganesan , Taylor Rod S , Poree Lawrence , Brounstein Dan , Duarte Rui V , Gmel Gerrit E , Gorman Robert , Gould Ian , Hanson Erin , Karantonis Dean M , Khurram Abeer , Leitner Angela , Mugan Dave , Obradovic Milan , Ouyang Zhonghua , Parker John , Single Peter , Soliday Nicole 
Published: August 2023

Introduction

The evidence for spinal cord stimulation (SCS) has been criticized for the absence of blinded, parallel randomized controlled trials (RCTs) and limited evaluations of the long-term effects of SCS in RCTs. The aim of this study was to determine whether evoked compound action potential (ECAP)-controlled, closed-loop SCS (CL-SCS) is associated with better outcomes when compared with fixed-output, open-loop SCS (OL-SCS) 36 months following implant.

Methods

The EVOKE study was a multicenter, participant-blinded, investigator-blinded, and outcome assessor-blinded, randomized, controlled, parallel-arm clinical trial that compared ECAP-controlled CL-SCS with fixed-output OL-SCS. Participants with chronic, intractable back and leg pain refractory to conservative therapy were enrolled between January 2017 and February 2018, with follow-up through 36 months. The primary outcome was a reduction of at least 50% in overall back and leg pain. Holistic treatment response, a composite outcome including pain intensity, physical and emotional functioning, sleep, and health-related quality of life, and objective neural activation was also assessed.

Results

At 36 months, more CL-SCS than OL-SCS participants reported ≥50% reduction (CL-SCS=77.6%, OL-SCS=49.3%; difference: 28.4%, 95% CI 12.8% to 43.9%, p<0.001) and ≥80% reduction (CL-SCS=49.3%, OL-SCS=31.3%; difference: 17.9, 95% CI 1.6% to 34.2%, p=0.032) in overall back and leg pain intensity. Clinically meaningful improvements from baseline were observed at 36 months in both CL-SCS and OL-SCS groups in all other patient-reported outcomes with greater levels of improvement with CL-SCS. A greater proportion of patients with CL-SCS were holistic treatment responders at 36-month follow-up (44.8% vs 28.4%), with a greater cumulative responder score for CL-SCS patients. Greater neural activation and accuracy were observed with CL-SCS. There were no differences between CL-SCS and OL-SCS groups in adverse events. No explants due to loss of efficacy were observed in the CL-SCS group.

Conclusion

This long-term evaluation with objective measurement of SCS therapy demonstrated that ECAP-controlled CL-SCS resulted in sustained, durable pain relief and superior holistic treatment response through 36 months. Greater neural activation and increased accuracy of therapy delivery were observed with ECAP-controlled CL-SCS than OL-SCS.

Trial registration number

NCT02924129.