The SMART trial was a randomized, sham-controlled, double-blind, study (ClinicalTrials.gov—NCT01446419) that was conducted between October 2011 and February 2014. This single-arm, open-label, prospective, follow-up study includes the 5-year outcomes for the US treated patients from the original RCT. The SMART Five Year Follow-up Study is registered on ClinicalTrials.gov as NCT03997825 and was sponsored by Relievant Medsystems, Inc. (Minneapolis, MN). The study was HIPAA compliant and conducted under institutional review board approval and participant informed consent. Enrolled patients maintained their assigned unique participant ID number from the original RCT for comparisons. To reduce potential sources of bias, a central independent research nurse collected all study data. Treatment success was adjudicated by an independent orthopedic surgeon. A third-party statistician (Technomics Research LLC, Minneapolis, MN) conducted the analysis. There were no revisions to the study protocol during the study.
The primary requirements for inclusion in the original RCT were CLBP with a duration greater than 6 months; CLBP nonresponsive to at least 6 months of nonsurgical management; and Modic Type 1 or 2 changes at the vertebral endplates of the levels targeted for treatment. Detailed information about the original study design and randomization process is to be found in the previously published material . An independent panel of three spine surgeons oversaw study enrollment including a review of baseline MRIs for the presence of Modic and evaluation of medical records, clinical assessments, and spine x-rays for exclusion of nonvertebrogenic pain etiologies such as spine instability, stenosis, and nerve impingement. Full inclusion and exclusion criteria confirmed by the panel of independent reviewers are listed in Table 1.
The original SMART RCT study design allowed sham-controlled arm patients the option of crossing to BVN ablation after 1 year of follow-up; 73% of patients elected to cross to treatment, thus preventing an adequate control sample and a lack of statistical power for future between group comparisons. Due to the high rate of crossover, the RCT converted to a single-arm intrapatient comparison in BVN ablation arm patients after 12 months.
This 5-year follow-up study was conducted in the USA at the 13 study sites that treated patients in the original RCT. Of the 133 US patients treated with BVN ablation, 117 were successfully treated and targeted and comprise the per protocol (PP) population for this study. An assessment of potential bias with a USA only study population was conducted. No statistical differences in baseline values or observed clinical outcomes at the 3-month primary endpoint were noted between this US PP study population and the global PP population of the original RCT with a change in ODI of − 17.45 in the non-US patients compared to − 20.77 in US patients (p < 0.4996).
Follow-up study visit
US treated patients were contacted by study centers to participate in the study. A minimum of two contacts followed by a certified letter was required. The study consisted of a single telephonic study visit between June 2019 and November 2019 (a minimum of 5-year post-BVN ablation). Self-reported patient outcomes were collected via interview using validated questionnaires that were sent in advance of the visit. Data were entered electronically into a secure online clinical database by the independent research nurse.
The BVN ablation was performed under image guidance in an outpatient setting using the Intracept ® System (Relievant Medsystems, Minneapolis, MN, USA). The target zone for BVN ablation is midline in the posterior aspect of the vertebral body, typically between 31 and 50% from the posterior to anterior of the vertebral body. Mean operative times of 60–90 min were recorded. Detailed information about the surgical technique was previously described . No additional interventions were required in the five plus year follow-up study.
MR imaging (T1, T2, and STIR time constants) was performed at 6-week post-RF ablation. Measurements of the degree of overlap between the RF ablation lesion and the terminus of the BVN for each VB were taken by an independent, blinded neuroradiologist reviewer. Targeting success was based on a defined threshold of observed overlap.
Functional impact was measured using the Oswestry disability index (ODI) questionnaire . Low back pain was assessed using a Visual Analog Scale (VAS)  ranging from 0 (no pain) to 10 (worst pain imaginable). Additional data elements collected were treatments performed post-BVN ablation, opioid use in the past 30 days, activity levels, and patient satisfaction. The primary endpoint of this study was a comparison of the minimum of 5-year patient-reported ODI compared to baseline. Baseline was defined as the last nonmissing assessment at or before the baseline visit and prior to BVN ablation treatment. Medical records and imaging for surgeries/pain interventions were reviewed by an independent orthopedic surgeon and adjudicated for treatment failure; defined as the same treatment location and etiology as the BVN procedure.
The analysis population was those US treatment arm patients who had successful targeting and provided data at 5 years or more; no participants had imputed data. Assessment for bias in the 5-year study results was conducted. Descriptive statistics of the baseline characteristics of the 5-year study population were means, standard deviations (SDs), number of observations (N), and 95% confidence intervals (CIs) for continuous variables, and percentages, Ns, and 95% CIs for categorical variables. Analysis of covariance (ANCOVA) was used for the primary effectiveness endpoint; the change from baseline in ODI score at the last follow-up was analyzed as a function of the baseline ODI score (the covariate). The analyses of secondary endpoints used descriptive statistics as described for the baseline characteristics (above), except for the VAS analysis and the analysis of the regression to the mean. The VAS analysis used an ANCOVA analogous to the primary endpoint. The regression to the mean analysis compared the 12- and 24-month postprocedure results (control and treatment arms) to the 5-year results using t tests of the ODI and VAS scores. An alpha level of 0.05 was used for significance for analyses.
Procedure and targeting success
Procedure success for all randomized patients was previously described in the RCT . All 133 US treatment arm patients were treated except for one patient with extremely dense bone at S1. In the 132 US treated patients, 117 (88.6%) were adjudicated as successful for targeting and comprise the US PP study population for this study.
Demographics and baseline characteristics
Retention rates were high in this study with 100 of the 117 US PP treated patients (85%) available for review at a mean follow-up of 6.4 years (range 5.4–7.8 years). See Fig. 1 for patient disposition.
Mean age was 47 years, 58% were male, and 69% had experienced low back pain for > 5 years prior to the procedure. In this study population, 80% of patients had 2 VBs treated and 20% had three VBs ablated. The most commonly treated VBs were L5 (98%) and S1 (75%) followed by L4 (42%). A comparison between patients participating in this study (N = 100) and the US PP patients that did not participate in the 5-year study visit (N = 17) was made. There were no statistically significant differences noted in baseline values or observed clinical outcomes at 3 months between these two groups. See Tables 2 and 3.
Long-term results for ODI improvement, VAS improvement, and responder rates were all statistically significant following treatment with BVN ablation.
ODI (primary endpoint)
At a minimum of 5 years following BVN ablation, patients reported a significant mean reduction in ODI of 25.95 ± 18.54 (60.6%) compared to a baseline of 42.81 (p < 0.001). See Fig. 2.
VAS pain scores
Mean reduction in VAS at 5-year post-BVN ablation was significant at 4.38 ± 2.35 points on a 10-point scale from a baseline of 6.74 (p < 0.001). Sixty-six percent (66%) of patients reported a > 50% reduction in VAS, 47% reported a > 75% reduction in VAS, and 34% of patients reported complete pain resolution. See Fig. 3.
Using a 15-point improvement in ODI, a commonly accepted minimum clinically important difference (MCID) for functional impact in the treatment of CLBP [17, 18], 77% (77/100) of treated patients exhibited a successful response (p < 0.001) at 5 years following BVN ablation. Using a 2-point improvement in VAS, the commonly accepted minimum clinically important difference (MCID) for pain in the treatment of CLBP , 88% (88/100) of treated patients reported a successful response. A combined responder rate of 75% was demonstrated using thresholds of ≥ 15-point ODI and ≥ 2-point VAS improvements for function and pain at 5 years following BVN ablation.
Clinically meaningful function and pain levels observed in the treatment arm patients at 1 and 2 years in the original RCT are sustained beyond 5 years of follow-up. See Figs. 4 and 5. Incremental differences between 24-month and 5-year outcomes were statistically significant with a mean incremental reduction of ODI of 3.33 (p < 0.016) and a mean VAS improvement of 0.79 (p < 0.002).
Post-BVN ablation healthcare utilization
At baseline 30/100 patients (30%) were actively taking opioids at least once a week. At 5 years, only 8/100 patients (8%) were actively taking opioids, a reduction of 73%. An additional 4/100 patients (4%) were taking opioids less than 1 time per week.
Injections were also significantly reduced in this group of patients at 5 years compared to baseline. At baseline, 59/100 patients (59%) had received an injection in the prior 12 months. At 5 years, only 4/100 patients (4%) had received injections in the prior 12 months. Only one of these (1%) was for the same treatment location and etiology for which BVN ablation was undertaken.
Twenty-one patients had surgery, or an interventional pain procedure performed in the mean of 6.4-year post-BVN ablation. Ten of these were adjudicated by the independent reviewer as not related to the original CLBP for which the patient underwent the BVN procedure and included L2 burst fracture (1), spinal stenosis (1), spondylolysis at different level (1), disk herniation at a different level (4), and spondylosis at a different level (3). Eleven (11%) were adjudicated as related to the original location and etiology of axial back pain and included fusion (8) and facet RF ablation (3). There were no patient-reported complications at the 5-year follow-up.
To understand any potential impact of additional treatments on clinical outcomes, an analysis was performed between the “as-treated” and the “BVN ablation only” populations in this study. There were no significant differences in 5-year outcomes noted with ODI reductions or pain scores between these two groups. See Table 4.
Patients reported a high degree of patient satisfaction: 70% (70/100) rated their condition as improved; 27% reported no change; and 3% indicated their condition had worsened. Seventy-nine percent (79%) of patients indicated they would have the BVN ablation again for the same condition, and 65% reported that they had resumed their level of activity that they had enjoyed prior to low back pain.