Basivertebral Nerve Ablation

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Over the past few decades, research has increasingly focused on the vertebral endplates (VEPs) – the interface between the intervertebral disc and the vertebral body – as a potential source of CLBP (See Vertebrogenic Low Back Pain). Damage to the VEPs, often associated with degenerative processes, can lead to inflammation and pain signaling, a condition termed vertebrogenic pain. Pain signals originating from these damaged endplates are transmitted via the basivertebral nerve (BVN), a nerve trunk that enters the posterior vertebral body and branches extensively to innervate the superior and inferior endplates. Histological studies have confirmed the presence of nociceptive fibers within the BVN and VEPs, with increased density observed in patients with CLBP and degenerative changes

Procedure

Basivertebral nerve ablation (BVNA) is a minimally invasive procedure developed to treat vertebrogenic CLBP by targeting the BVN. The most studied system for performing BVNA is the Intracept™ Intraosseous Nerve Ablation System. The procedure involves accessing the vertebral body via a transpedicular approach under imaging guidance (typically fluoroscopy). A channel is created towards the terminus of the BVN, near the center of the vertebral body. A radiofrequency (RF) probe is then introduced, and RF energy is applied (typically at 85 °C for 15 minutes) to create a thermal lesion, thereby ablating the BVN and interrupting the transmission of pain signals from the damaged endplates. The procedure is typically performed in an outpatient setting and is implant-free. The Intracept system has received FDA 510(k) clearance in the US and is CE marked in the EU for its intended use.  

Evidence

There are two primary Level I RCTs:

1. SMART Trial: A double-blind, sham-controlled, prospective, multi-centre randomised trial by Fischgrund et al. supported the efficacy of BVNA, reporting a mean ODI reduction of 20.5 points in the treatment group compared to 15.2 points in the sham group at 3 months, with 75.6% of patients achieving a clinically meaningful improvement at 3 months. The magnitude of clinical improvement was found to be similar to that of fusion and total disc replacement surgery.
2. INTRACEPT Trial: Khalil et al. conducted a prospective, multi-centre, randomized, open label controlled trial comparing BVNA to standard care, showing that BVNA led to a mean ODI reduction of 25.3 points and a VAS reduction of 3.46 cm at 3 months, with 74.5% of patients achieving a ≥10-point improvement in ODI.. At 12 months, patients in the BVNA group showed a mean reduction in the 0-100 point Oswestry Disability Index (ODI) of 25.7 points and a mean reduction in a 0-10 point Visual Analog Scale (VAS) pain score of 3.8, with 64% of patients achieving at least a 50% reduction in pain.

The SMART Trial (Sham-Controlled)

Design and Methodology

The SMART trial was a rigorously designed, prospective, multi-center, randomized, double-blind, sham-controlled study conducted across 15 US and 3 European sites. A total of 225 patients were randomized in a 2:1 ratio to receive either BVNA (n=147) or a sham procedure (n=78). The sham procedure involved mimicking the operative setup and duration, including docking an introducer cannula into the pedicle, but without creating the channel to the BVN or delivering RF energy, aiming to maintain patient and follow-up investigator blinding.¹³ The primary endpoint was the mean change in the Oswestry Disability Index (ODI) from baseline to 3 months post-procedure. Patients were evaluated at multiple time points up to 12 months within the randomized phase, with provisions for sham patients to cross over to active treatment after the 12-month evaluation.

Patient Population

Participants were skeletally mature adults (mean age 47 years) with isolated CLBP of at least 6 months duration that had failed to respond to at least 6 months of non-operative management. A critical inclusion criterion was the presence of Type 1 or Type 2 Modic changes on MRI at one or more vertebral levels between L3 and S1. Patients were required to have a baseline ODI score of at least 30 points and a Visual Analog Scale (VAS) pain score of at least 4 cm, indicating moderate to severe pain and disability. Stringent exclusion criteria were applied to ensure a homogenous population with likely vertebrogenic pain, excluding those with radicular pain, symptomatic spinal stenosis, significant disc herniation or spondylolisthesis, prior lumbar surgery, osteoporosis, or significant psychosocial factors like depression or litigation.

Efficacy Results

At the 3-month primary endpoint, the results showed a statistically significant difference favoring BVNA over sham in the per-protocol (PP) population. The mean ODI reduction was 20.5 points in the BVNA arm compared to 15.2 points in the sham arm (p=0.019). Responder analysis using a 10-point ODI decrease threshold also favored the BVNA arm (75.6% vs 55.3%) in the PP population.

However, a notable characteristic of this trial was the substantial improvement observed in the sham group (15.2 point ODI reduction at 3 months). This significant placebo/sham effect complicated the interpretation, particularly for the intent-to-treat (ITT) population analysis, where the difference between groups at 3 months was less pronounced or did not achieve statistical significance according to some sources. This highlights the challenge of demonstrating efficacy over sham for procedural interventions in CLBP, where non-specific effects can be substantial.

VAS pain scores also showed improvement, though specific comparative data at 3 months between arms is less consistently reported in the provided abstracts than ODI data.

Long-Term Follow-up (BVNA Arm)

The BVNA treatment arm was followed prospectively beyond the initial 12-month randomized phase.

• 2-Year Follow-up: Data from 106 patients in the PP treatment group showed sustained improvements. The mean ODI reduction from baseline was 23.4 points (53.7% improvement), and the mean VAS reduction was 3.59 cm (52.9% improvement). Responder rates remained high, with 76.4% achieving 10-point ODI improvement and 70.2% achieving 1.5 cm VAS improvement.
• 5-Year Follow-up: A subsequent analysis focused on the US cohort of the BVNA treatment arm (n=100 available, 85% retention) with a mean follow-up of 6.4 years. Significant improvements from baseline were maintained: mean ODI reduction of 25.95 points (p<0.001) and mean VAS reduction of 4.38 points (p<0.001). At this time point, 66% reported >50% pain reduction, 47% reported >75% pain reduction, and 34% reported complete pain resolution (VAS=0). The composite responder rate (using thresholds of 15-point ODI and $\ge$2-point VAS) was 75%. Reductions in opioid use (73% reduction in active use) and spinal injections were also noted compared to baseline.

It is crucial to note that these 2-year and 5-year results reflect outcomes within the originally treated BVNA arm only and lack a concurrent randomized control group. While suggestive of durability, these findings are subject to potential biases inherent in long-term uncontrolled follow-up studies.

Safety

The SMART trial reported a favorable safety profile for BVNA. No device or procedure-related deaths, unanticipated adverse device effects, or device-related serious adverse events (SAEs) were reported during the 2-year follow-up period.¹³ Procedure-related adverse events were generally minor, with some instances of transient nerve root injury/irritation or lumbar radiculopathy reported across both arms.³⁷ Imaging follow-up showed no evidence of adverse spinal cord changes, avascular necrosis, or accelerated disc degeneration.

The INTRACEPT Trial (Standard Care Controlled)

Design and Methodology

The INTRACEPT trial was a prospective, multi-center, randomized, open-label study conducted at 23 US sites. A total of 140 eligible patients were randomized 1:1 to either BVNA plus continued standard care (SC) (n=66) or SC alone (n=74). Standard care was determined via shared decision-making and could include various non-surgical modalities. The primary endpoint was the between-arm comparison of mean ODI change from baseline at 3 months. An interim analysis was pre-specified, and due to demonstrated superiority of BVNA, the Data Monitoring Committee recommended offering BVNA to the SC arm patients earlier than initially planned. Subsequently, 92% of the SC arm patients elected to cross over and receive BVNA.

Patient Population

Eligibility criteria were similar to the SMART trial, requiring CLBP for 6 months, failure of conservative care, and MRI evidence of Type 1 or 2 Modic changes between L3 and S1. The patient population characteristics were also comparable, with a mean age around 50 years, severe baseline disability (mean ODI ~46), moderate-to-severe baseline pain (mean VAS ~6.8), and a long duration of symptoms. Patients had typically undergone multiple prior conservative treatments.

Efficacy Results

The INTRACEPT trial demonstrated statistically significant and clinically meaningful superiority of BVNA over SC at the primary 3-month endpoint and subsequent time points within the randomized phase.

• 3 Months: The mean ODI reduction difference between arms was -20.3 points favoring BVNA (p<0.001). The mean VAS reduction difference was -2.5 cm favoring BVNA (p<0.001). ODI responder rates (15 points) were significantly higher for BVNA (69.2% vs 20.8%, p<0.001).
• 6 Months: Superiority was maintained, with an ODI reduction difference of -24.5 points (p<0.001) and a VAS reduction difference of -3.3 cm (p<0.001) favoring BVNA. Combined pain and function responder rates also strongly favored BVNA (58.3% vs 6.0%, p<0.001).

Follow-up (BVNA Arm and Crossover Group)

• BVNA Arm (12 Months): Patients originally randomized to BVNA continued to show significant improvements from baseline, with a mean ODI reduction of 25.7 points and a mean VAS reduction of 3.8 cm (both p<0.001). At 12 months, 64% reported 50% VAS reduction, and 29% were pain-free. Quality of life measures (SF-36, EQ-5D-5L) also showed significant improvements.
• BVNA Arm (24 Months): Follow-up data available for 58 patients (88% retention) showed sustained benefits. Mean ODI improved by 28.5 points and mean VAS by 4.1 cm from baseline (both p<0.001). Over 72% reported 50% pain reduction, and 31% were pain-free.
• Crossover Group (6 Months Post-BVNA): The former SC patients who received BVNA demonstrated significant improvements from their re-baseline assessment. Mean ODI reduction was 25.9 points (p<0.001), and mean VAS reduction was 3.8 cm (p<0.001). Responder rates were also high in this group. These results mirror those seen in the original BVNA arm, suggesting reproducibility of the treatment effect.

An interesting finding from the RCT phase was that the proportion of patients using opioids did not significantly change between the BVNA and SC arms at the 6-month comparison (p=0.56). This contrasts with longer-term, uncontrolled follow-up data from pooled analyses which suggest reductions in opioid use over time post-BVNA.

Guidelines

The American Society of Pain and Neuroscience guidelines highlight that BVNA provides significant improvements in pain, function, and quality of life, with sustained benefits over several years and a favorable safety profile.[4-5] The guidelines designate the evidence as being Grade A with Certainty 1a based upon four randomised controlled trials.

Adverse Events

Adverse events are generally considered to be rare and minor. The American Society of Pain and Neuroscience guidelines state that the most common side effect is pain and transient worsening, which generally resolves with time. Transient nerve injury or inflammation can occur in approximately 1 in 100 cases. Serious adverse events are rare including fracture (one case reported in the surveillance data), serious haemorrhage (one case reported in the surveillance data), nerve root or plexus injury (3 cases reported). Infection is theoretically possible but there have been no reported cases. There have also been no reported cases of spinal cord injury or accelerated disc degeneration.

Long-term Data

Long-term data for basivertebral nerve ablation (BVNA) in the treatment of chronic low back pain associated with Modic changes indicates sustained efficacy and safety over extended follow-up periods.

A study by Fischgrund et al. reported 5-year outcomes from a prospective, randomized, double-blind, sham-controlled trial. The results showed a mean reduction in Oswestry Disability Index (ODI) of 25.95 points and a mean reduction in Visual Analog Scale (VAS) pain score of 4.38 points. Additionally, 66% of patients reported a >50% reduction in pain, and 34% reported complete pain resolution.

Smuck et al. pooled long-term outcomes from two prospective clinical trials, demonstrating significant improvements in pain and function at 3 years post-BVNA. The mean reduction in Numeric Pain Scores (NPS) was 4.3 points, and the mean reduction in ODI was 31.2 points. Responder rates for ≥15-point ODI improvement and ≥50% pain reduction were 85.3% and 72.6%, respectively.

Limitations

While the two Level I RCTs provide important evidence, several limitations should be acknowledged. Both pivotal trials were funded by the device manufacturer (Relievant Medsystems, now Boston Scientific), which introduces potential for bias. The interpretation of the SMART trial is complicated by the significant sham effect. The INTRACEPT trial's open-label design and use of standard care as a comparator limit definitive conclusions about efficacy specifically attributable to BVN ablation beyond non-specific effects or comparison to a less intensive intervention.

Furthermore, the compelling long-term durability data comes primarily from uncontrolled follow-up of the treatment arms. Systematic reviews based on this evidence generally conclude that there is moderate-quality evidence supporting BVNA's effectiveness for reducing pain and disability in appropriately selected patients, but also call for further high-quality research. Payer policies have varied, with some initially considering the procedure investigational due to the perceived limitations in the evidence base, although clinical guidelines like those from ISASS support its use in appropriately selected patients.  

A final concern is the very high cost of the INTRACEPT system (reportedly over 10-15,000 as a single use disposable system). There have been pragmatic modifications of the technique to allow the use of standard radiofrequency equipment, such as bipolar lesioning.

Resources

BVNA pooled analysis - Khalil 2024.pdf - 2.16 MB (f)