Long-term quality of life improvement for chronic intractable back and leg pain patients using spinal cord stimulation: 12-month results from the SENZA-RCT

Long-term quality of life improvement for chronic intractable back and leg pain patients using... Purpose Chronic axial low-back pain is a debilitating disorder that impacts all aspects of an afflicted individual’s life. Effec- tive, durable treatments have historically been elusive. Interventional therapies, such as spinal cord stimulation (SCS), have shown limited efficacy at best. Recently, a novel treatment, 10 kHz SCS, has demonstrated superior pain relief compared with traditional SCS in a randomized controlled trial (RCT). In this manuscript, we report on the long-term improvements in quality of life (QoL) outcomes for subjects enrolled in this study. Methods A prospective, multicenter, randomized controlled trial (SENZA-RCT) was conducted. Patients with both chronic back and leg pain were enrolled and randomized (1:1) into 10 kHz SCS or traditional SCS treatment groups. A total of 171 subjects received a permanent SCS device implant. QoL and functionality measures were collected up to 12 months. The device remote control utilization, which is an indication of patient interaction with the device for adjustments, was collected at 24-month post-implantation. Results At 12 months, a higher proportion of 10 kHz SCS subjects had marked improvement of their disability (Oswestry Disability Index) to a “moderate” or “minimal” impact on their daily function versus the control group. The subjects also reported better improvement in the Global Assessment of Functioning, Clinician Global Impression of Change, Pittsburgh Sleep Quality Index, and short-form McGill Pain Questionnaire, compared to traditional SCS subjects. The 10 kHz SCS subjects also reported far higher rates of both driving and sleeping with their device turned on, as well as reduced reliance on their programmers to adjust therapy settings. Conclusions In addition to superior pain relief, 10 kHz SCS provides long-term improvements in quality of life and func- tionality for subjects with chronic low-back and leg pain. Trial registration: ClinicalTrials.gov (NCT01609972). Keywords Spinal cord stimulation · Quality of life · Neuropathic pain · 10 kHz · High-frequency SCS · Chronic low-back pain · Leg pain * Jeyakumar Subbaroyan Center for Clinical Research and Carolina’s Pain Institute jey.subbaroyan@nevro.com at Brookstown, Wake Forest Baptist Health, Winston-Salem, NC, USA IPM Medical Group, Inc., Walnut Creek, CA, USA Millennium Pain Center, Bloomington, IL, USA Swedish Pain Center, Seattle, WA, USA Advanced Pain Therapy, PLLC, Hattiesburg, MS, USA The Pain Center of Arizona and HOPE Research Institute, Comprehensive Pain and Rehabilitation, Pascagoula, MS, Phoenix, AZ, USA USA Clinical Affairs, Nevro Corp., 1800 Bridge Parkway, Coastal Orthopedics and Pain Medicine, Bradenton, FL, Redwood City, CA 94065, USA USA Pain Specialists of Oregon, Eugene, OR, USA Vol.:(0123456789) 1 3 Quality of Life Research parameters results in paresthesia-free pain relief with Introduction 10  kHz SCS. In a multicenter, randomized controlled trial (SENZA-RCT), 10 kHz SCS demonstrated superior, For the past two decades, low-back pain has been the sin- long-lasting back and leg pain relief, when compared to gle leading cause of disability worldwide, affecting 9.2% traditional, low-frequency SCS without the need for pain- of the population [1, 2]. Chronic, intractable back pain paresthesia overlap [22, 23]. At 12 months, the responder dramatically affects one’s work function, activities of rates (≥ 50% pain relief) for the 10  kHz SCS and low- daily living, as well as social relationships with friends frequency SCS were 76.5% and 49.3% for back pain and and family members. In addition, the global pervasive- 72.9% and 49.3% for leg pain, respectively. Pain relief ness and intractable nature of this ailment, as the leading is the primary goal when treating subjects with chronic cause of disability in the population, results in tremendous pain; however, there are secondary measures that reflect healthcare utilization [3–5] and loss of workforce produc- the subjects’ overall well-being and functionality. Out- tivity [6, 7]. Treatments for chronic pain currently include comes related to QoL, as assessed by appropriate meas- exercise, physical therapy, psychological support, phar- ures of functionality, sleep, pain interference, and subject maceuticals, interventional procedures, neuromodulation, satisfaction, elucidate a more comprehensive picture of the and surgery. However, the evidence of efficacy of such subjects’ disposition [10, 15, 24–28]. We present data col- treatments is limited for many chronic pain patients [8]. lected during the SENZA-RCT, demonstrating improved Thus, there is great need for improved treatment options functionality and QoL outcomes for subjects treated with for patients living with chronic low-back and leg pain, in 10 kHz SCS therapy. order to not only reduce their pain, but to also improve their quality of life (QoL). Spinal cord stimulation (SCS) is a well-established Methods treatment option for chronic neuropathic pain arising from various etiologies [9–12]. Traditional SCS utilizes This study was registered with ClinicalTrials.gov an array of electrodes placed in the epidural space to (NCT01609972) on May 30th, 2012 and conducted in com- deliver low-frequency (∼50 Hz) electrical stimulation to pliance with the United States Code of Federal Regulations the dorsal column nerve fibers. This therapy depends on and in accordance with recommendations of the 18th World the induction of paresthesias (tingling or buzzing sen- Medical Assembly (Helsinki, Finland) guiding physicians in sations) overlapping the patient’s pain distribution [13]. biomedical research. Both the study protocol and informed Paresthesias are caused by the activation of large diameter consent were approved by each participating site’s govern- Aβ fibers [14]. While it has been found to be an effective ing institutional review board (Western Institutional Review treatment for chronic, intractable neuropathic pain [15, Board, Puyallup, Washington; Forsyth Medical Center Insti- 16], published evidence demonstrates that pain relief from tutional Review Board, Winston-Salem, North Carolina). All traditional SCS may not be sustained over the long-term. subjects enrolled in the study provided written, informed Moreover, traditional SCS may not effectively treat axial consent prior to their participation. low-back pain [15, 17–19]. The arrangement of dorsal A total of 198 subjects with both back and leg pain were column fibers innervating the axial back makes it diffi- randomized 1:1 to either low-frequency, traditional SCS or cult to elicit paresthesias in this region using traditional 10 kHz SCS across ten comprehensive pain treatment cent- SCS. Moreover, the intensity of these paresthesias can ers in the United States. Detailed methods, including sub- also vary, based on body position resulting in either a ject demographics and subject flow diagram, are described sudden, uncomfortable increase in stimulation or persis- elsewhere [29]. Briefly, a pair of percutaneous leads was tent unwanted sensations [20, 21]. This precludes the use placed in the dorsal epidural space along the radiographic of traditional SCS during sleeping, driving, and operat- midline of the spinal column and stimulation was trialed ing machinery. Thus, there remains great potential for for up to 14 days. Of the subjects randomized, 189 com- improved efficacy of neuromodulation as an attractive pleted the trial phase and 171 of those had a successful alternative to both conventional medical management and trial, defined as ≥ 40% reduction in back pain as measured more invasive surgical procedures. by the 10-cm visual analog scale (VAS). The subjects with Recently, a neuromodulation therapy utilizing a high- successful trials were implanted with a permanent SCS frequency, 10 kHz stimulation waveform (HF10 therapy) system, 90 with 10 kHz SCS (Senza System; Nevro Corp., has emerged as a promising therapeutic option. This USA) and 81 with traditional SCS (Precision Plus System; therapy involves percutaneous leads placed in the epi- Boston Scientific, USA). Of the 198 subjects (101–10 kHz, dural space, similar to traditional SCS. But a combina- 97—low-frequency SCS) randomized to trial stimulation, tion of anatomical midline lead placement and stimulation 1 3 Quality of Life Research a total of 9 were not trialed (4–10 kHz SCS and 5—low- could be surrogate marker for good pain relief and quality frequency SCS) for the following reasons: 10 kHz SCS— of life. medical contraindication (2), withdrawal of consent (1), Data are presented as the median and 95% confidence lost to follow-up (1); low-frequency SCS—withdrawal of interval (CI) of the median. In outcomes where no base- consent (4), medical contraindication (1). Only those with line values are available for comparison, data are presented a successful trial (≥ 40% pain relief) proceeded to perma- as median and their interquartile range (IQR). Categorical nent implant (10 kHz SCS—90 or 92.8%; low-frequency variables were compared using either Fisher’s exact test or SCS—81 or 88.0%). Mann–Whitney test if there was evidence of non-normality Under the guidance of the study investigators, SCS in the data. This study was powered for the primary end- devices were programmed by representatives of the respec- point of responder rate with a hierarchical testing proce- tive company according to their best practices. Low-back and dure performed for secondary endpoints (all of which were leg pain scores (VAS) were collected at all follow-up visits, determined to be significant) [29]. The quality of life out- in addition to measures of functionality [Oswestry Disability comes reported in the current manuscript were tertiary or Index (ODI) and Global Assessment of Functioning (GAF)], observational outcomes, and therefore were not subject to pain interference [Short Form McGill Pain Questionnaire hierarchical testing. As such, we report nominal p values (SF-MPQ-2)], and sleep quality [Pittsburgh Sleep Quality without correction. Index (PSQI)]. Overall well-being [Short Form Health Sur- vey (SF-12) and Global Impression of Change (GIC)] data were also captured at baseline and 12-month post-permanent Results device implant. ODI assesses the level of disability as “minimal,” “mod- Oswestry Low‑Back Pain Disability Questionnaire erate,” “severe,” “crippled,” or “bed bound,” [30] while GAF (ODI) categorizes symptoms that affect social, occupational, and school activities as “none,” “minimal,” “transient,” “mild,” There was no difference between the two groups in baseline “moderate,” or “serious” [31]. SF-MPQ-2 measures both ODI scores, whether analyzing average raw scores (dif- neuropathic and non-neuropathic (affective) pain associated ference in medians: 2.00 [95% CI 0.00–5.33], p = .141, with a disease condition [32]. GIC assesses the change in exact non-parametric Mann–Whitney test, 2-sided) or dis- severity of a subject’s pain over time and involves both a tribution of subjects among the subcategories (p = .228, patient’s report as well as a clinician’s evaluation [33, 34]. exact non-parametric Mann–Whitney test, 2-sided). At PSQI assesses seven subscales related to sleep that together 12 months, however, there was a notable improvement for add up to a global score [35]. the 10 kHz SCS group compared with traditional SCS sub- ODI has been validated in a low-back pain population jects in both average raw scores (difference in medians: [30, 36], whereas SF-MPQ-2 was validated for use in clini- 6.00 [95% CI 1.56–11.12], p = .016, exact non-parametric cal research with neuropathic and non-neuropathic pain con- Mann–Whitney test, 2-sided) and distribution of subjects ditions [32]. SF-12 is an established, generic measure of among the subcategories (p = .010, exact non-parametr ic health status used in various disease conditions [37]. All of Mann–Whitney test, 2-sided) (Fig. 1). Within the 10 kHz the above listed questionnaires along with GIC were recom- SCS group, 69.6% of subjects had an improved ODI score mended health-related quality of life (HRQOL) outcomes in sufficient to reclassify them into a lower disability cate- chronic pain trials by the Initiative on Methods, Measure- gory, whereas 55.1% of traditional SCS subjects were in ment and Pain Assessment in Clinical Trials (IMMPACT) a lower disability grouping at 12 months (Table 1). The [38]. Current traditional SCS therapies can cause sudden specific distribution of subjects among subcategories has changes in paresthesias with activities as the position of the been previously reported [29]. stimulating electrode and spinal cord varies [39]. Frequent interaction with the device, by changing the stimulation Global Assessment of Functioning (GAF) or turning the therapy off to avoid unwanted shocks, may be perceived as burdensome to patient’s normal daily rou- Baseline scores were 65.00 (IQR 15.00) and 65.00 (IQR tine. To explore this question, subjects returning for their 18.25) for 10 kHz SCS and traditional SCS groups, respec- 24-month follow-up visit were asked how often they used tively (difference in median: 0.00 [95% CI − 2.00–5.00], their remote programmers and whether they carried it with p = .511). Improvement in GAF scores at 12 months com- them when they left the house. Also, the continuous usage pared to baseline was 14.00 (IQR 15.00) in the 10 kHz SCS of stimulation including while sleeping and during activi- group and 6.50 (IQR 19.00) in the traditional SCS group. ties without having to frequently change stimulation settings Therefore, improvement in GAF scores for 10  kHz SCS 1 3 Quality of Life Research Fig. 1 Distribution of subjects amongst the subcategories of Oswestry Disability Index (ODI) in the traditional SCS and 10 kHz SCS groups at baseline and at 12 months Table 1 The number and percentage of subjects stratified into “minimal,” “moderate,” “severe,” “crippled”, or “bedbound” categories by the ODI administered at baseline and 12 months A. Traditional SCS 12 months N = 80 Minimal Moderate Severe Crippled Baseline  Minimal – – – –  Moderate 1 (1.3%) 0 0 0  Severe 6 (7.5%) 25 (31.3%) 28 (35.0%) 2 (2.5%)  Crippled 0 5 (6.3%) 7 (8.8%) 6 (7.5%)  Bedbound – – – – B. 10 kHz SCS 12 months N = 89 Minimal Moderate Severe Crippled Baseline  Minimal – – – –  Moderate 4 (4.5%) 4 (4.5%) 0 0  Severe 9 (10.1%) 32 (36.0%) 21 (23.6%) 1 (1.1%)  Crippled 2 (2.2%) 5 (5.6%) 10 (11.2%) 1 (1.1%)  Bedbound – – – – The number of subjects who improved from baseline are in normal font, the number with no change from baseline are in Italics, and the number who worsened are in bold. For traditional SCS subjects (A), 44 (55.1%) improved by at least one category. For 10  kHz SCS subjects (B), 62 (69.6%) improved by one or more categories group was higher than that reported in the traditional SCS groups at 12 months revealed that 10 kHz SCS subjects group (difference in medians: 5.00, [95% CI 0.10–10.00], reported greater improvements than their traditional SCS p < .01, Mann–Whitney test). The specific distribution of counterparts in continuous (difference in medians: 1.17, subjects among subcategories has been previously reported [95% CI 2.00–0.50], p < .005), inter mittent (difference [29]. in medians: 1.33, [95% CI 2.00–0.50], p < .005), and neuropathic pain (difference in medians: 0.83, [95% CI Short Form McGill Pain Questionnaire 2 (SF‑MPQ‑2) 1.50–0.17], p < .01, Mann–Whitney non-parametric test). However, there was no difference between the treatment Compared to their respective baseline values, both tradi- groups on the affective disorders subscale (Fig.  2, dif- tional SCS and 10 kHz SCS subjects reported reductions ference in medians: 0.25, [95% CI 0.00–0.75], p = .080, in all components of pain and affective disorder subscales Mann–Whitney non-parametric test). on the SF-MPQ-2. Comparisons between the two treatment 1 3 Quality of Life Research “better” or “a great deal better,” compared to 75.0% of 10 kHz SCS subjects (Fig. 4B, p = .009, Fisher’s exact test, 2-sided). Sleeping or driving with stimulation on At 12 months, 82 of 86, or 95.3%, of the 10 kHz SCS sub- jects reported leaving the stimulator on while sleeping, whereas 41 of 69, or 59.4%, of the traditional SCS subjects did the same (Table 2, p < .001, Fisher’s exact test, 2-sided). Seventy six of 81, or 93.8%, of the 10 kHz SCS subjects also reported that they drive with the stimulator turned on, compared to 40 of 61, or 65.6%, of traditional SCS subjects who reported doing the same (Table  2, p < .001, Fisher’s exact test, 2-sided). Pittsburgh Sleep Quality Assessment (PSQI) The PSQI collects data from seven 4-point subscales that collectively make up the global score. On 6 of the 7 sub- scales, a higher proportion of 10 kHz SCS subjects improved compared with traditional SCS subjects. The improvement with 10 kHz SCS subjects was noted to be in subjective sleep quality, improved sleep latency and duration, better habitual sleep efficiency, reduced use of sleep medications, Fig. 2 Average scores at baseline and 12 months assessed by the SF- and less daytime dysfunction. A PSQI global score of 5 or MPQ-2. Data are presented as median and interquartile range with greater indicates poor sleep quality. There was no difference upper and lower bounds for the subscales of continuous pain (A), neu- between the two groups in proportion of “good sleepers” ropathic pain (B), intermittent pain (C), and affective descriptors (D ) to “poor sleepers” at baseline (p = .587, Fisher’s exact test, 2-sided). At 12 months, there was no increase in the number 12 Item Short Form Survey (SF‑12) of traditional SCS subjects with good sleep quality but there was an observable increase in the number of “good sleepers” The results of the SF-12 questionnaire are reported as two among the 10 kHz SCS group compared to traditional SCS subjects (p = .001, Fisher’s exact test, 2-sided). separate subscale scores: a physical health composite score (PCS) and a mental health composite score (MCS). Both Reliance on Patient Remote Programmer the traditional and 10 kHz SCS groups showed improve- ment from baseline in their PCS and MCS (Fig. 3). In PCS, At 24 months, subjects were asked to complete an optional the differences in medians for 10 kHz SCS and traditional SCS were 7.97 [95% CI 5.72–10.39] and 6.20 [95% CI survey about their use and reliance on their programmer, including if they took it outside of their homes and if they 3.70–8.78], respectively. In MCS, the differences in medi- ans for 10 kHz SCS and traditional SCS were 3.77 [95% used it daily (n = 55 for 10 kHz SCS and n = 40 for tradi- tional SCS). Approximately 85% of the subjects treated CI 0.13–7.53] and 2.10 [95% CI 1.26–5.55], respectively. There was no statistical difference between the groups in with traditional SCS, reported carrying their programmer outside of their homes and 35.4% used their programmers either score. daily. Only 38.2% of 10 kHz SCS subjects carried the device with them when they left the house. None of the 10 kHz SCS Global Impression of Change (GIC) subjects used their remote programming device daily. On the Patient Global Impression of Change (PGIC) question- naire collected at 12 months, 42.0% of traditional SCS subjects Discussion reported feeling “better” or “a great deal better,” compared to 57.3% of 10 kHz SCS subjects (Fig. 4A, p = .052, Fisher’s When evaluating treatments for chronic, intractable pain, exact test, 2-sided). On the Clinician Global Impression of Change (CGIC) questionnaire collected at 12 months, 56.5% the paramount focus should be on the magnitude of reduc- tion in pain scores. However, improvement in quality of life of traditional SCS subjects were rated by their physician as 1 3 Quality of Life Research Fig. 3 Subject well-being as captured at baseline and the 12-month follow-up with the SF-12 questionnaire and reported as two separate sub- scale scores: a physical health composite score (PCS) and a mental health composite score (MCS) metrics may not be neglected, as they add a comprehensive populations and may lack the sensitivity to detect a differ - overview at patient’s overall function and well-being. The ence between the SENZA-RCT treatment groups [40]. In SENZA-RCT not only demonstrated superior pain relief for addition, the SENZA-RCT was powered for the primary 10 kHz SCS subjects with chronic low-back and leg pain endpoint of responder rates and not the secondary, QoL compared to subjects treated with traditional SCS [29], but it endpoints. Thus, a larger sample size may be necessary to also demonstrated greater improvements across a variety of detect differences on the SF-12 questionnaire. Similarly, QoL measures, including the ODI, GAF, SF-MPQ-2, GIC, this study was not powered to detect differences in sleep PSQI, and subject remote programmer usage. quality as measured by the PSQI, although we do see a One assay, the SF-12, showed improvements from notable increase in the number of 10 kHz SCS subjects at baseline, but did not statistically differ between the two 12 months who score in the “good sleeper” category on the treatment groups. This instrument is designed to meas- global scale, while there was no change for traditional SCS ure QoL and functionality in a wide variety of patient subjects. A larger sample size may help elucidate which 1 3 Quality of Life Research Fig. 4 The percentage of subjects categorized into “a great deal bet- A) and the clinician (CGIC, B). The total percentage of subjects ter,” “better,” “moderately better,” “somewhat better,” “a little bet- whose change from baseline was classified as either “a great deal bet- ter,” “almost the same,” or “no change” by the GIC administered at ter” or “better” is indicated next to each bar 12 months. This assessment is completed by both the patient (PGIC, Table 2 Subject device usage while sleeping or driving also explain the difference in device usage (10 kHz SCS: 24 ± 0.1 h/day versus traditional SCS: 17.0 ± 7.3 h/day). Traditional SCS 10 kHz SCS Another concept which may help interpret clinical out- N = 69 N = 86 comes and simplify treatment algorithms would be to estab- Sleep with stimulation turned on? lish what constitutes a minimal clinically important differ -  Yes 41 (59.4%) 82 (95.3%) ence (MCID) for a variety of measures commonly used in  No 28 (40.6%) 4 (4.7%) chronic pain research. MCID is defined as “The smallest dif - Drive with stimulation turned on? ference in score in the domain of interest which patients per-  Yes 40 (65.6%) 76 (93.8%) ceive as beneficial and which would mandate, in the absence  No 21 (34.4%) 5 (6.2%) of troublesome side effects and excessive cost, a change  NA 8 5 in the patient’s management” [43]. Few studies assessing SCS therapy have examined MCID in functional and QoL Results of subject questionnaire at 12  months about SCS use during sleep and while driving. Data are reported as N (%). NA indicates outcomes. Defining MCID threshold for QoL assessments subjects that do not drive; thus, the percentages are based on only would help identify what level of score improvement an subjects who drive intervention is of noticeable benefit to the patient; therefore, potentially worth the attendant risks. For the ODI, several specific aspects of sleep quality improve for 10 kHz SCS studies have defined a range of absolute value changes in the overall score as an MCID [44–48]. An analysis of the subjects. It is noteworthy that this scale has been shown to correlate strongly with measures of depression, anxiety, SENZA-RCT ODI data per the MCID definitions estab- lished in these studies demonstrate the responder rates for stress, and a negative outlook [41, 42]. Traditional SCS subjects reported much higher daily both traditional SCS and 10 kHz SCS subjects at 12 months which is depicted in Fig. 5. Regardless of how conservative usage of their programmers and were more likely to carry it with them than subjects being treated with 10 kHz SCS. the definition of the MCID is, approximately 10–15% more 10 kHz SCS subjects achieved an MCID than their tradi- This suggests that those being treated with 10 kHz were less burdened by the needs of the therapy. It is possible that tional SCS counterparts. Presenting the data in this manner, as the proportion of subjects who report a MCID from their the uncomfortable paresthesia reported in the traditional SCS group could have attributed to this behavior. Majority baseline score, will provide a standard by which a physician can evaluate the clinical significance of an improved score. (95.5%) of subjects receiving traditional SCS experienced paresthesia and of those, 11.1% found it uncomfortable and Further research to establish MCID thresholds for additional QoL assessments would be of tremendous value. 39.7% experienced discomfort with changes in posture. The uncomfortable paresthesia elicited by traditional SCS could 1 3 Quality of Life Research Compliance with ethical standards Conflict of interest KA: Personal fees from Nevro Corp., Saluda Medical, and Abbott. Grants from Nevro Corp., Mesoblast, Abbott, Saluda and Biotronik. Scientific advisory board member of Mesoblast, Nalu Medical and Biotronik. CY: Personal fees from Boston Scientific, Medtronic, and St. Jude Medical. LK: Grants from Nevro Corp., Bos- ton Scientific, and Saluda Medical and personal fees from Medtronic, Stimwave and St. Jude Medical. BEG, ESB, AAP and JS: Employees of Nevro Corp. RV: Grants from Nevro Corp. and Boston Scientific and personal fees from Boston Scientific. RB (Coastal Orthopedics and Pain Medicine): Personal fees (speaking engagements) and re- search grants from Nevro Corp. TLY: Research grants from Boston Scientific, Nevro Corp., and St. Jude Medical; Consulting agreements with Boston Scientific, Nevro Corp., St. Jude Medical and Neuronano; Officer in Meagan Medical (Chief Medical Officer) and Algos Clini- cal Development (Director). RB (Millennium Pain Center): Consulting agreement with Medtronic; Research Grants from Medtronic, Boston Fig. 5 The percentage of subjects achieving an improvement in ODI Scientific, St. Jude Medical and Nevro Corp. TY: Consulting agree- score that meets or exceeds the definition of a MCID, as previously ment with Nevro Corp. MWD, DMM, BTS, AHB: No conflict. defined in the literature. The difference between comparable bars is shown above each pair Ethical approval This study was registered with ClinicalTrials.gov (NCT01609972) on May 30th, 2012 and conducted in compliance with the United States Code of Federal Regulations and in accordance Prior publications have demonstrated the safety, effi - with recommendations of the 18th World Medical Assembly (Helsinki, cacy, and stability of 10 kHz SCS for long-term treatment Finland) guiding physicians in biomedical research. Both the study pro- of chronic, intractable pain of the trunk and limbs, includ- tocol and informed consent were approved by each participating site’s governing institutional review board (Western Institutional Review ing the axial low-back [23, 29, 49]. Results presented here Board, Puyallup, Washington; Forsyth Medical Center Institutional further demonstrate that 10 kHz SCS markedly improves Review Board, Winston-Salem, North Carolina). secondary outcomes that reflect the subjects’ better health, functionality, and overall well-being. The higher subject Informed consent All subjects enrolled in the study provided written, informed consent prior to their participation. satisfaction scores could be due to the absence of paresthe- sias with 10 kHz SCS and/or the superior, stable pain relief. Based on the available data, it is reasonable to postulate that Open Access This article is distributed under the terms of the Crea- tive Commons Attribution 4.0 International License (http://creat iveco a high degree of pain relief, in the absence of paresthesias, mmons.or g/licenses/b y/4.0/), which permits unrestricted use, distribu- enables the subjects to carry out daily activities, including tion, and reproduction in any medium, provided you give appropriate driving and sleeping, without experiencing unwanted stim- credit to the original author(s) and the source, provide a link to the ulation from postural changes, a common complaint with Creative Commons license, and indicate if changes were made. traditional low-frequency SCS systems [50, 51]. A limitation of the study was that these tertiary endpoints were not powered to assess multiple hypothesis tests. 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Long-term quality of life improvement for chronic intractable back and leg pain patients using spinal cord stimulation: 12-month results from the SENZA-RCT

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Medicine & Public Health; Quality of Life Research; Sociology, general; Public Health; Quality of Life Research
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Abstract

Purpose Chronic axial low-back pain is a debilitating disorder that impacts all aspects of an afflicted individual’s life. Effec- tive, durable treatments have historically been elusive. Interventional therapies, such as spinal cord stimulation (SCS), have shown limited efficacy at best. Recently, a novel treatment, 10 kHz SCS, has demonstrated superior pain relief compared with traditional SCS in a randomized controlled trial (RCT). In this manuscript, we report on the long-term improvements in quality of life (QoL) outcomes for subjects enrolled in this study. Methods A prospective, multicenter, randomized controlled trial (SENZA-RCT) was conducted. Patients with both chronic back and leg pain were enrolled and randomized (1:1) into 10 kHz SCS or traditional SCS treatment groups. A total of 171 subjects received a permanent SCS device implant. QoL and functionality measures were collected up to 12 months. The device remote control utilization, which is an indication of patient interaction with the device for adjustments, was collected at 24-month post-implantation. Results At 12 months, a higher proportion of 10 kHz SCS subjects had marked improvement of their disability (Oswestry Disability Index) to a “moderate” or “minimal” impact on their daily function versus the control group. The subjects also reported better improvement in the Global Assessment of Functioning, Clinician Global Impression of Change, Pittsburgh Sleep Quality Index, and short-form McGill Pain Questionnaire, compared to traditional SCS subjects. The 10 kHz SCS subjects also reported far higher rates of both driving and sleeping with their device turned on, as well as reduced reliance on their programmers to adjust therapy settings. Conclusions In addition to superior pain relief, 10 kHz SCS provides long-term improvements in quality of life and func- tionality for subjects with chronic low-back and leg pain. Trial registration: ClinicalTrials.gov (NCT01609972). Keywords Spinal cord stimulation · Quality of life · Neuropathic pain · 10 kHz · High-frequency SCS · Chronic low-back pain · Leg pain * Jeyakumar Subbaroyan Center for Clinical Research and Carolina’s Pain Institute jey.subbaroyan@nevro.com at Brookstown, Wake Forest Baptist Health, Winston-Salem, NC, USA IPM Medical Group, Inc., Walnut Creek, CA, USA Millennium Pain Center, Bloomington, IL, USA Swedish Pain Center, Seattle, WA, USA Advanced Pain Therapy, PLLC, Hattiesburg, MS, USA The Pain Center of Arizona and HOPE Research Institute, Comprehensive Pain and Rehabilitation, Pascagoula, MS, Phoenix, AZ, USA USA Clinical Affairs, Nevro Corp., 1800 Bridge Parkway, Coastal Orthopedics and Pain Medicine, Bradenton, FL, Redwood City, CA 94065, USA USA Pain Specialists of Oregon, Eugene, OR, USA Vol.:(0123456789) 1 3 Quality of Life Research parameters results in paresthesia-free pain relief with Introduction 10  kHz SCS. In a multicenter, randomized controlled trial (SENZA-RCT), 10 kHz SCS demonstrated superior, For the past two decades, low-back pain has been the sin- long-lasting back and leg pain relief, when compared to gle leading cause of disability worldwide, affecting 9.2% traditional, low-frequency SCS without the need for pain- of the population [1, 2]. Chronic, intractable back pain paresthesia overlap [22, 23]. At 12 months, the responder dramatically affects one’s work function, activities of rates (≥ 50% pain relief) for the 10  kHz SCS and low- daily living, as well as social relationships with friends frequency SCS were 76.5% and 49.3% for back pain and and family members. In addition, the global pervasive- 72.9% and 49.3% for leg pain, respectively. Pain relief ness and intractable nature of this ailment, as the leading is the primary goal when treating subjects with chronic cause of disability in the population, results in tremendous pain; however, there are secondary measures that reflect healthcare utilization [3–5] and loss of workforce produc- the subjects’ overall well-being and functionality. Out- tivity [6, 7]. Treatments for chronic pain currently include comes related to QoL, as assessed by appropriate meas- exercise, physical therapy, psychological support, phar- ures of functionality, sleep, pain interference, and subject maceuticals, interventional procedures, neuromodulation, satisfaction, elucidate a more comprehensive picture of the and surgery. However, the evidence of efficacy of such subjects’ disposition [10, 15, 24–28]. We present data col- treatments is limited for many chronic pain patients [8]. lected during the SENZA-RCT, demonstrating improved Thus, there is great need for improved treatment options functionality and QoL outcomes for subjects treated with for patients living with chronic low-back and leg pain, in 10 kHz SCS therapy. order to not only reduce their pain, but to also improve their quality of life (QoL). Spinal cord stimulation (SCS) is a well-established Methods treatment option for chronic neuropathic pain arising from various etiologies [9–12]. Traditional SCS utilizes This study was registered with ClinicalTrials.gov an array of electrodes placed in the epidural space to (NCT01609972) on May 30th, 2012 and conducted in com- deliver low-frequency (∼50 Hz) electrical stimulation to pliance with the United States Code of Federal Regulations the dorsal column nerve fibers. This therapy depends on and in accordance with recommendations of the 18th World the induction of paresthesias (tingling or buzzing sen- Medical Assembly (Helsinki, Finland) guiding physicians in sations) overlapping the patient’s pain distribution [13]. biomedical research. Both the study protocol and informed Paresthesias are caused by the activation of large diameter consent were approved by each participating site’s govern- Aβ fibers [14]. While it has been found to be an effective ing institutional review board (Western Institutional Review treatment for chronic, intractable neuropathic pain [15, Board, Puyallup, Washington; Forsyth Medical Center Insti- 16], published evidence demonstrates that pain relief from tutional Review Board, Winston-Salem, North Carolina). All traditional SCS may not be sustained over the long-term. subjects enrolled in the study provided written, informed Moreover, traditional SCS may not effectively treat axial consent prior to their participation. low-back pain [15, 17–19]. The arrangement of dorsal A total of 198 subjects with both back and leg pain were column fibers innervating the axial back makes it diffi- randomized 1:1 to either low-frequency, traditional SCS or cult to elicit paresthesias in this region using traditional 10 kHz SCS across ten comprehensive pain treatment cent- SCS. Moreover, the intensity of these paresthesias can ers in the United States. Detailed methods, including sub- also vary, based on body position resulting in either a ject demographics and subject flow diagram, are described sudden, uncomfortable increase in stimulation or persis- elsewhere [29]. Briefly, a pair of percutaneous leads was tent unwanted sensations [20, 21]. This precludes the use placed in the dorsal epidural space along the radiographic of traditional SCS during sleeping, driving, and operat- midline of the spinal column and stimulation was trialed ing machinery. Thus, there remains great potential for for up to 14 days. Of the subjects randomized, 189 com- improved efficacy of neuromodulation as an attractive pleted the trial phase and 171 of those had a successful alternative to both conventional medical management and trial, defined as ≥ 40% reduction in back pain as measured more invasive surgical procedures. by the 10-cm visual analog scale (VAS). The subjects with Recently, a neuromodulation therapy utilizing a high- successful trials were implanted with a permanent SCS frequency, 10 kHz stimulation waveform (HF10 therapy) system, 90 with 10 kHz SCS (Senza System; Nevro Corp., has emerged as a promising therapeutic option. This USA) and 81 with traditional SCS (Precision Plus System; therapy involves percutaneous leads placed in the epi- Boston Scientific, USA). Of the 198 subjects (101–10 kHz, dural space, similar to traditional SCS. But a combina- 97—low-frequency SCS) randomized to trial stimulation, tion of anatomical midline lead placement and stimulation 1 3 Quality of Life Research a total of 9 were not trialed (4–10 kHz SCS and 5—low- could be surrogate marker for good pain relief and quality frequency SCS) for the following reasons: 10 kHz SCS— of life. medical contraindication (2), withdrawal of consent (1), Data are presented as the median and 95% confidence lost to follow-up (1); low-frequency SCS—withdrawal of interval (CI) of the median. In outcomes where no base- consent (4), medical contraindication (1). Only those with line values are available for comparison, data are presented a successful trial (≥ 40% pain relief) proceeded to perma- as median and their interquartile range (IQR). Categorical nent implant (10 kHz SCS—90 or 92.8%; low-frequency variables were compared using either Fisher’s exact test or SCS—81 or 88.0%). Mann–Whitney test if there was evidence of non-normality Under the guidance of the study investigators, SCS in the data. This study was powered for the primary end- devices were programmed by representatives of the respec- point of responder rate with a hierarchical testing proce- tive company according to their best practices. Low-back and dure performed for secondary endpoints (all of which were leg pain scores (VAS) were collected at all follow-up visits, determined to be significant) [29]. The quality of life out- in addition to measures of functionality [Oswestry Disability comes reported in the current manuscript were tertiary or Index (ODI) and Global Assessment of Functioning (GAF)], observational outcomes, and therefore were not subject to pain interference [Short Form McGill Pain Questionnaire hierarchical testing. As such, we report nominal p values (SF-MPQ-2)], and sleep quality [Pittsburgh Sleep Quality without correction. Index (PSQI)]. Overall well-being [Short Form Health Sur- vey (SF-12) and Global Impression of Change (GIC)] data were also captured at baseline and 12-month post-permanent Results device implant. ODI assesses the level of disability as “minimal,” “mod- Oswestry Low‑Back Pain Disability Questionnaire erate,” “severe,” “crippled,” or “bed bound,” [30] while GAF (ODI) categorizes symptoms that affect social, occupational, and school activities as “none,” “minimal,” “transient,” “mild,” There was no difference between the two groups in baseline “moderate,” or “serious” [31]. SF-MPQ-2 measures both ODI scores, whether analyzing average raw scores (dif- neuropathic and non-neuropathic (affective) pain associated ference in medians: 2.00 [95% CI 0.00–5.33], p = .141, with a disease condition [32]. GIC assesses the change in exact non-parametric Mann–Whitney test, 2-sided) or dis- severity of a subject’s pain over time and involves both a tribution of subjects among the subcategories (p = .228, patient’s report as well as a clinician’s evaluation [33, 34]. exact non-parametric Mann–Whitney test, 2-sided). At PSQI assesses seven subscales related to sleep that together 12 months, however, there was a notable improvement for add up to a global score [35]. the 10 kHz SCS group compared with traditional SCS sub- ODI has been validated in a low-back pain population jects in both average raw scores (difference in medians: [30, 36], whereas SF-MPQ-2 was validated for use in clini- 6.00 [95% CI 1.56–11.12], p = .016, exact non-parametric cal research with neuropathic and non-neuropathic pain con- Mann–Whitney test, 2-sided) and distribution of subjects ditions [32]. SF-12 is an established, generic measure of among the subcategories (p = .010, exact non-parametr ic health status used in various disease conditions [37]. All of Mann–Whitney test, 2-sided) (Fig. 1). Within the 10 kHz the above listed questionnaires along with GIC were recom- SCS group, 69.6% of subjects had an improved ODI score mended health-related quality of life (HRQOL) outcomes in sufficient to reclassify them into a lower disability cate- chronic pain trials by the Initiative on Methods, Measure- gory, whereas 55.1% of traditional SCS subjects were in ment and Pain Assessment in Clinical Trials (IMMPACT) a lower disability grouping at 12 months (Table 1). The [38]. Current traditional SCS therapies can cause sudden specific distribution of subjects among subcategories has changes in paresthesias with activities as the position of the been previously reported [29]. stimulating electrode and spinal cord varies [39]. Frequent interaction with the device, by changing the stimulation Global Assessment of Functioning (GAF) or turning the therapy off to avoid unwanted shocks, may be perceived as burdensome to patient’s normal daily rou- Baseline scores were 65.00 (IQR 15.00) and 65.00 (IQR tine. To explore this question, subjects returning for their 18.25) for 10 kHz SCS and traditional SCS groups, respec- 24-month follow-up visit were asked how often they used tively (difference in median: 0.00 [95% CI − 2.00–5.00], their remote programmers and whether they carried it with p = .511). Improvement in GAF scores at 12 months com- them when they left the house. Also, the continuous usage pared to baseline was 14.00 (IQR 15.00) in the 10 kHz SCS of stimulation including while sleeping and during activi- group and 6.50 (IQR 19.00) in the traditional SCS group. ties without having to frequently change stimulation settings Therefore, improvement in GAF scores for 10  kHz SCS 1 3 Quality of Life Research Fig. 1 Distribution of subjects amongst the subcategories of Oswestry Disability Index (ODI) in the traditional SCS and 10 kHz SCS groups at baseline and at 12 months Table 1 The number and percentage of subjects stratified into “minimal,” “moderate,” “severe,” “crippled”, or “bedbound” categories by the ODI administered at baseline and 12 months A. Traditional SCS 12 months N = 80 Minimal Moderate Severe Crippled Baseline  Minimal – – – –  Moderate 1 (1.3%) 0 0 0  Severe 6 (7.5%) 25 (31.3%) 28 (35.0%) 2 (2.5%)  Crippled 0 5 (6.3%) 7 (8.8%) 6 (7.5%)  Bedbound – – – – B. 10 kHz SCS 12 months N = 89 Minimal Moderate Severe Crippled Baseline  Minimal – – – –  Moderate 4 (4.5%) 4 (4.5%) 0 0  Severe 9 (10.1%) 32 (36.0%) 21 (23.6%) 1 (1.1%)  Crippled 2 (2.2%) 5 (5.6%) 10 (11.2%) 1 (1.1%)  Bedbound – – – – The number of subjects who improved from baseline are in normal font, the number with no change from baseline are in Italics, and the number who worsened are in bold. For traditional SCS subjects (A), 44 (55.1%) improved by at least one category. For 10  kHz SCS subjects (B), 62 (69.6%) improved by one or more categories group was higher than that reported in the traditional SCS groups at 12 months revealed that 10 kHz SCS subjects group (difference in medians: 5.00, [95% CI 0.10–10.00], reported greater improvements than their traditional SCS p < .01, Mann–Whitney test). The specific distribution of counterparts in continuous (difference in medians: 1.17, subjects among subcategories has been previously reported [95% CI 2.00–0.50], p < .005), inter mittent (difference [29]. in medians: 1.33, [95% CI 2.00–0.50], p < .005), and neuropathic pain (difference in medians: 0.83, [95% CI Short Form McGill Pain Questionnaire 2 (SF‑MPQ‑2) 1.50–0.17], p < .01, Mann–Whitney non-parametric test). However, there was no difference between the treatment Compared to their respective baseline values, both tradi- groups on the affective disorders subscale (Fig.  2, dif- tional SCS and 10 kHz SCS subjects reported reductions ference in medians: 0.25, [95% CI 0.00–0.75], p = .080, in all components of pain and affective disorder subscales Mann–Whitney non-parametric test). on the SF-MPQ-2. Comparisons between the two treatment 1 3 Quality of Life Research “better” or “a great deal better,” compared to 75.0% of 10 kHz SCS subjects (Fig. 4B, p = .009, Fisher’s exact test, 2-sided). Sleeping or driving with stimulation on At 12 months, 82 of 86, or 95.3%, of the 10 kHz SCS sub- jects reported leaving the stimulator on while sleeping, whereas 41 of 69, or 59.4%, of the traditional SCS subjects did the same (Table 2, p < .001, Fisher’s exact test, 2-sided). Seventy six of 81, or 93.8%, of the 10 kHz SCS subjects also reported that they drive with the stimulator turned on, compared to 40 of 61, or 65.6%, of traditional SCS subjects who reported doing the same (Table  2, p < .001, Fisher’s exact test, 2-sided). Pittsburgh Sleep Quality Assessment (PSQI) The PSQI collects data from seven 4-point subscales that collectively make up the global score. On 6 of the 7 sub- scales, a higher proportion of 10 kHz SCS subjects improved compared with traditional SCS subjects. The improvement with 10 kHz SCS subjects was noted to be in subjective sleep quality, improved sleep latency and duration, better habitual sleep efficiency, reduced use of sleep medications, Fig. 2 Average scores at baseline and 12 months assessed by the SF- and less daytime dysfunction. A PSQI global score of 5 or MPQ-2. Data are presented as median and interquartile range with greater indicates poor sleep quality. There was no difference upper and lower bounds for the subscales of continuous pain (A), neu- between the two groups in proportion of “good sleepers” ropathic pain (B), intermittent pain (C), and affective descriptors (D ) to “poor sleepers” at baseline (p = .587, Fisher’s exact test, 2-sided). At 12 months, there was no increase in the number 12 Item Short Form Survey (SF‑12) of traditional SCS subjects with good sleep quality but there was an observable increase in the number of “good sleepers” The results of the SF-12 questionnaire are reported as two among the 10 kHz SCS group compared to traditional SCS subjects (p = .001, Fisher’s exact test, 2-sided). separate subscale scores: a physical health composite score (PCS) and a mental health composite score (MCS). Both Reliance on Patient Remote Programmer the traditional and 10 kHz SCS groups showed improve- ment from baseline in their PCS and MCS (Fig. 3). In PCS, At 24 months, subjects were asked to complete an optional the differences in medians for 10 kHz SCS and traditional SCS were 7.97 [95% CI 5.72–10.39] and 6.20 [95% CI survey about their use and reliance on their programmer, including if they took it outside of their homes and if they 3.70–8.78], respectively. In MCS, the differences in medi- ans for 10 kHz SCS and traditional SCS were 3.77 [95% used it daily (n = 55 for 10 kHz SCS and n = 40 for tradi- tional SCS). Approximately 85% of the subjects treated CI 0.13–7.53] and 2.10 [95% CI 1.26–5.55], respectively. There was no statistical difference between the groups in with traditional SCS, reported carrying their programmer outside of their homes and 35.4% used their programmers either score. daily. Only 38.2% of 10 kHz SCS subjects carried the device with them when they left the house. None of the 10 kHz SCS Global Impression of Change (GIC) subjects used their remote programming device daily. On the Patient Global Impression of Change (PGIC) question- naire collected at 12 months, 42.0% of traditional SCS subjects Discussion reported feeling “better” or “a great deal better,” compared to 57.3% of 10 kHz SCS subjects (Fig. 4A, p = .052, Fisher’s When evaluating treatments for chronic, intractable pain, exact test, 2-sided). On the Clinician Global Impression of Change (CGIC) questionnaire collected at 12 months, 56.5% the paramount focus should be on the magnitude of reduc- tion in pain scores. However, improvement in quality of life of traditional SCS subjects were rated by their physician as 1 3 Quality of Life Research Fig. 3 Subject well-being as captured at baseline and the 12-month follow-up with the SF-12 questionnaire and reported as two separate sub- scale scores: a physical health composite score (PCS) and a mental health composite score (MCS) metrics may not be neglected, as they add a comprehensive populations and may lack the sensitivity to detect a differ - overview at patient’s overall function and well-being. The ence between the SENZA-RCT treatment groups [40]. In SENZA-RCT not only demonstrated superior pain relief for addition, the SENZA-RCT was powered for the primary 10 kHz SCS subjects with chronic low-back and leg pain endpoint of responder rates and not the secondary, QoL compared to subjects treated with traditional SCS [29], but it endpoints. Thus, a larger sample size may be necessary to also demonstrated greater improvements across a variety of detect differences on the SF-12 questionnaire. Similarly, QoL measures, including the ODI, GAF, SF-MPQ-2, GIC, this study was not powered to detect differences in sleep PSQI, and subject remote programmer usage. quality as measured by the PSQI, although we do see a One assay, the SF-12, showed improvements from notable increase in the number of 10 kHz SCS subjects at baseline, but did not statistically differ between the two 12 months who score in the “good sleeper” category on the treatment groups. This instrument is designed to meas- global scale, while there was no change for traditional SCS ure QoL and functionality in a wide variety of patient subjects. A larger sample size may help elucidate which 1 3 Quality of Life Research Fig. 4 The percentage of subjects categorized into “a great deal bet- A) and the clinician (CGIC, B). The total percentage of subjects ter,” “better,” “moderately better,” “somewhat better,” “a little bet- whose change from baseline was classified as either “a great deal bet- ter,” “almost the same,” or “no change” by the GIC administered at ter” or “better” is indicated next to each bar 12 months. This assessment is completed by both the patient (PGIC, Table 2 Subject device usage while sleeping or driving also explain the difference in device usage (10 kHz SCS: 24 ± 0.1 h/day versus traditional SCS: 17.0 ± 7.3 h/day). Traditional SCS 10 kHz SCS Another concept which may help interpret clinical out- N = 69 N = 86 comes and simplify treatment algorithms would be to estab- Sleep with stimulation turned on? lish what constitutes a minimal clinically important differ -  Yes 41 (59.4%) 82 (95.3%) ence (MCID) for a variety of measures commonly used in  No 28 (40.6%) 4 (4.7%) chronic pain research. MCID is defined as “The smallest dif - Drive with stimulation turned on? ference in score in the domain of interest which patients per-  Yes 40 (65.6%) 76 (93.8%) ceive as beneficial and which would mandate, in the absence  No 21 (34.4%) 5 (6.2%) of troublesome side effects and excessive cost, a change  NA 8 5 in the patient’s management” [43]. Few studies assessing SCS therapy have examined MCID in functional and QoL Results of subject questionnaire at 12  months about SCS use during sleep and while driving. Data are reported as N (%). NA indicates outcomes. Defining MCID threshold for QoL assessments subjects that do not drive; thus, the percentages are based on only would help identify what level of score improvement an subjects who drive intervention is of noticeable benefit to the patient; therefore, potentially worth the attendant risks. For the ODI, several specific aspects of sleep quality improve for 10 kHz SCS studies have defined a range of absolute value changes in the overall score as an MCID [44–48]. An analysis of the subjects. It is noteworthy that this scale has been shown to correlate strongly with measures of depression, anxiety, SENZA-RCT ODI data per the MCID definitions estab- lished in these studies demonstrate the responder rates for stress, and a negative outlook [41, 42]. Traditional SCS subjects reported much higher daily both traditional SCS and 10 kHz SCS subjects at 12 months which is depicted in Fig. 5. Regardless of how conservative usage of their programmers and were more likely to carry it with them than subjects being treated with 10 kHz SCS. the definition of the MCID is, approximately 10–15% more 10 kHz SCS subjects achieved an MCID than their tradi- This suggests that those being treated with 10 kHz were less burdened by the needs of the therapy. It is possible that tional SCS counterparts. Presenting the data in this manner, as the proportion of subjects who report a MCID from their the uncomfortable paresthesia reported in the traditional SCS group could have attributed to this behavior. Majority baseline score, will provide a standard by which a physician can evaluate the clinical significance of an improved score. (95.5%) of subjects receiving traditional SCS experienced paresthesia and of those, 11.1% found it uncomfortable and Further research to establish MCID thresholds for additional QoL assessments would be of tremendous value. 39.7% experienced discomfort with changes in posture. The uncomfortable paresthesia elicited by traditional SCS could 1 3 Quality of Life Research Compliance with ethical standards Conflict of interest KA: Personal fees from Nevro Corp., Saluda Medical, and Abbott. Grants from Nevro Corp., Mesoblast, Abbott, Saluda and Biotronik. Scientific advisory board member of Mesoblast, Nalu Medical and Biotronik. CY: Personal fees from Boston Scientific, Medtronic, and St. Jude Medical. LK: Grants from Nevro Corp., Bos- ton Scientific, and Saluda Medical and personal fees from Medtronic, Stimwave and St. Jude Medical. BEG, ESB, AAP and JS: Employees of Nevro Corp. RV: Grants from Nevro Corp. and Boston Scientific and personal fees from Boston Scientific. RB (Coastal Orthopedics and Pain Medicine): Personal fees (speaking engagements) and re- search grants from Nevro Corp. TLY: Research grants from Boston Scientific, Nevro Corp., and St. Jude Medical; Consulting agreements with Boston Scientific, Nevro Corp., St. Jude Medical and Neuronano; Officer in Meagan Medical (Chief Medical Officer) and Algos Clini- cal Development (Director). RB (Millennium Pain Center): Consulting agreement with Medtronic; Research Grants from Medtronic, Boston Fig. 5 The percentage of subjects achieving an improvement in ODI Scientific, St. Jude Medical and Nevro Corp. TY: Consulting agree- score that meets or exceeds the definition of a MCID, as previously ment with Nevro Corp. MWD, DMM, BTS, AHB: No conflict. defined in the literature. The difference between comparable bars is shown above each pair Ethical approval This study was registered with ClinicalTrials.gov (NCT01609972) on May 30th, 2012 and conducted in compliance with the United States Code of Federal Regulations and in accordance Prior publications have demonstrated the safety, effi - with recommendations of the 18th World Medical Assembly (Helsinki, cacy, and stability of 10 kHz SCS for long-term treatment Finland) guiding physicians in biomedical research. Both the study pro- of chronic, intractable pain of the trunk and limbs, includ- tocol and informed consent were approved by each participating site’s governing institutional review board (Western Institutional Review ing the axial low-back [23, 29, 49]. Results presented here Board, Puyallup, Washington; Forsyth Medical Center Institutional further demonstrate that 10 kHz SCS markedly improves Review Board, Winston-Salem, North Carolina). secondary outcomes that reflect the subjects’ better health, functionality, and overall well-being. The higher subject Informed consent All subjects enrolled in the study provided written, informed consent prior to their participation. satisfaction scores could be due to the absence of paresthe- sias with 10 kHz SCS and/or the superior, stable pain relief. Based on the available data, it is reasonable to postulate that Open Access This article is distributed under the terms of the Crea- tive Commons Attribution 4.0 International License (http://creat iveco a high degree of pain relief, in the absence of paresthesias, mmons.or g/licenses/b y/4.0/), which permits unrestricted use, distribu- enables the subjects to carry out daily activities, including tion, and reproduction in any medium, provided you give appropriate driving and sleeping, without experiencing unwanted stim- credit to the original author(s) and the source, provide a link to the ulation from postural changes, a common complaint with Creative Commons license, and indicate if changes were made. traditional low-frequency SCS systems [50, 51]. A limitation of the study was that these tertiary endpoints were not powered to assess multiple hypothesis tests. 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Quality of Life ResearchSpringer Journals

Published: Jun 1, 2018

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