TY - JOUR
T1 - Durable multimodal and holistic response for physiologic closed-loop spinal cord stimulation supported by objective evidence from the EVOKE double-blind randomized controlled trial
AU - Kapural, Leonardo
AU - Mekhail, Nagy A.
AU - Costandi, Shrif
AU - Gilmore, Christopher
AU - Pope, Jason E.
AU - Li, Sean
AU - Hunter, Corey W.
AU - Poree, Lawrence
AU - Staats, Peter S.
AU - Taylor, Rod S.
AU - Eldabe, Sam
AU - Kallewaard, Jan Willem
AU - Thomson, Simon
AU - Petersen, Erika A.
AU - Sayed, Dawood
AU - Deer, Timothy R.
AU - Antony, Ajay
AU - Budwany, Ryan
AU - Leitner, Angela
AU - Soliday, Nicole
AU - Duarte, Rui V.
AU - Levy, Robert M.
N1 - Funding Information: This study was supported by Saluda Medical. Publisher Copyright: © American Society of Regional Anesthesia & Pain Medicine 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.
PY - 2023
Y1 - 2023
N2 - Introduction: Chronic pain patients may experience impairments in multiple health-related domains. The design and interpretation of clinical trials of chronic pain interventions, however, remains primarily focused on treatment effects on pain intensity. This study investigates a novel, multidimensional holistic treatment response to evoked compound action potential-controlled closed-loop versus open-loop spinal cord stimulation as well as the degree of neural activation that produced that treatment response. Methods: Outcome data for pain intensity, physical function, health-related quality of life, sleep quality and emotional function were derived from individual patient level data from the EVOKE multicenter, participant, investigator, and outcome assessor-blinded, parallel-arm randomized controlled trial with 24 month follow-up. Evaluation of holistic treatment response considered whether the baseline score was worse than normative values and whether minimal clinical important differences were reached in each of the domains that were impaired at baseline. A cumulative responder score was calculated to reflect the total minimal clinical important differences accumulated across all domains. Objective neurophysiological data, including spinal cord activation were measured. Results: Patients were randomized to closed-loop (n=67) or open-loop (n=67). A greater proportion of patients with closed-loop spinal cord stimulation (49.3% vs 26.9%) were holistic responders at 24-month follow-up, with at least one minimal clinical important difference in all impaired domains (absolute risk difference: 22.4%, 95% CI 6.4% to 38.4%, p=0.012). The cumulative responder score was significantly greater for closed-loop patients at all time points and resulted in the achievement of more than three additional minimal clinical important differences at 24-month follow-up (mean difference 3.4, 95% CI 1.3 to 5.5, p=0.002). Neural activation was three times more accurate in closed-loop spinal cord stimulation (p<0.001 at all time points). Conclusion: The results of this study suggest that closed-loop spinal cord stimulation can provide sustained clinically meaningful improvements in multiple domains and provide holistic improvement in the long-term for patients with chronic refractory pain. Trial registration number: NCT02924129.
AB - Introduction: Chronic pain patients may experience impairments in multiple health-related domains. The design and interpretation of clinical trials of chronic pain interventions, however, remains primarily focused on treatment effects on pain intensity. This study investigates a novel, multidimensional holistic treatment response to evoked compound action potential-controlled closed-loop versus open-loop spinal cord stimulation as well as the degree of neural activation that produced that treatment response. Methods: Outcome data for pain intensity, physical function, health-related quality of life, sleep quality and emotional function were derived from individual patient level data from the EVOKE multicenter, participant, investigator, and outcome assessor-blinded, parallel-arm randomized controlled trial with 24 month follow-up. Evaluation of holistic treatment response considered whether the baseline score was worse than normative values and whether minimal clinical important differences were reached in each of the domains that were impaired at baseline. A cumulative responder score was calculated to reflect the total minimal clinical important differences accumulated across all domains. Objective neurophysiological data, including spinal cord activation were measured. Results: Patients were randomized to closed-loop (n=67) or open-loop (n=67). A greater proportion of patients with closed-loop spinal cord stimulation (49.3% vs 26.9%) were holistic responders at 24-month follow-up, with at least one minimal clinical important difference in all impaired domains (absolute risk difference: 22.4%, 95% CI 6.4% to 38.4%, p=0.012). The cumulative responder score was significantly greater for closed-loop patients at all time points and resulted in the achievement of more than three additional minimal clinical important differences at 24-month follow-up (mean difference 3.4, 95% CI 1.3 to 5.5, p=0.002). Neural activation was three times more accurate in closed-loop spinal cord stimulation (p<0.001 at all time points). Conclusion: The results of this study suggest that closed-loop spinal cord stimulation can provide sustained clinically meaningful improvements in multiple domains and provide holistic improvement in the long-term for patients with chronic refractory pain. Trial registration number: NCT02924129.
KW - chronic pain
KW - spinal cord stimulation
KW - treatment outcome
UR - http://www.scopus.com/inward/record.url?scp=85166435573&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/rapm-2023-104639
DO - https://doi.org/10.1136/rapm-2023-104639
M3 - Article
C2 - 37491149
SN - 1098-7339
JO - Regional anesthesia and pain medicine
JF - Regional anesthesia and pain medicine
M1 - e104639
ER -