A Prospective Study to Evaluate the Efficacy of Iovera Lumbar Medial Branch Cryoneurolysis Versus Radiofrequency Ablation for the Treatment of Chronic Low Back Pain

Secondary objectives of this study include:

1. Evaluate safety outcomes (i.e., adverse device effects, serious adverse device effects, and adverse events) related to iovera° treatment;
2. Evaluate clinical outcomes related to iovera° treatment including pain, functional disability, and concomitant medication use (including opioids and analgesics);
3. Evaluate the treatment success and failure rate of iovera° medial branch cryoneurolysis;
4. Evaluate health-related quality of life (HRQoL);
5. Evaluate subject satisfaction with pain management;
6. Identify subgroups of patients who are most and least likely to benefit from iovera° medial branch cryoneurolysis for facet-mediated CLBP.

An adaptive study design will be used in this study. A blinded interim analysis will occur after approximately 56 total subjects, at least 28 per study arm, have completed assessment data for the primary efficacy outcome. The primary purpose of this interim analysis is to evaluate the sample size assumptions.

• Iovera Medial Branch Cryoneurolysis (Device): The iovera group will receive fluoroscopic guided medial branch cryoneurolysis with the subject in the prone position under asepsis: * Investigator injects 1% lidocaine at the treatment site using a 25-gauge, 3/4 -inch needle to numb the skin and tissue around the facet joint * Introducer needle is inserted through the skin wheal to the target medial branch nerve below the junction of the superior articular and transverse process * The introducer needle is positioned, and an x-ray image is taken to confirm the needle's position * With the desired introducer needle position confirmed, the iovera Smart Tip is guided through the introducer needle and the handpiece is secured to the Smart Tip. The start/stop button on the iovera° handpiece is then pressed to start the cycle. * After the cycle is complete, Smart Tip can be removed and next treatment cycle can commence ensuring an overlap of the ice ball * The needle is removed, and light compression is applied with gauze
• Radiofrequency ablation (RFA) (Procedure): Subjects will receive a fluoroscopic guided RFA medial branch block in the prone position under asepsis: * The Right L4, L5, S1 articular pillars are identified with fluoroscopy at each level and the target points are located * A skin wheal is formed using 5mL 1% Lidocaine and 5mL 0.25% Bupivacaine * A 20-gauge, 10cm needle with a 10mm active tip is inserted using a 15-degree oblique view and a 15-degree caudad angle onto the waist of each pillar at each level * Anterior-posterior and oblique neuroforamen views confirm positioning * Stimulation is performed and recorded to confirm proper needle placement * A mixture of 3mL of 0.25% Bupivacaine and 2mL of 1% Lidocaine is divided and injected at each level * A lesion is then performed at each level at 80 degrees centigrade for 60 seconds * The needles are removed, and bandages applied to the puncture sites * The same procedure is carried out on the opposite side

Primary outcomes

• Numeric rating scale (NRS) pain intensity score [360 days after intervention]: Subjects will evaluate their pain in the low back region using an 11-point NRS where 0=no pain and 10=worst possible pain, such that higher scores are associated with greater pain intensity. * Pain intensity scores (using the NRS) measured as "On a scale from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, how much pain are you experiencing in your low back right now? * Pain intensity scores (using the numeric rating scale; NRS) measured as "On a scale from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, what was the worst pain in your low back in the last 24 hours?" * Pain intensity scores (using the NRS) measured as "On a scale from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, what was the average pain in your low back in the last 24 hours?" Mean numeric pain intensity rating scores will be summarized by study arm using basic descriptive statistics.

Secondary outcomes

• Change in Functional Disability from baseline using Oswestry Disability Questionnaire [360 days after intervention]: The Oswestry Disability Questionnaire is a 10-item condition-specific measure of functional status (pain and disability) for patients with low back pain (LBP). Each question has 6 possible answers (0 = worse, 5 = best). The raw score is doubled to provide a percent score from 0 to 100%; with 0 equaling no disability and 100% equaling the worst possible outcome. It measures pain-related disability. Change from baseline scores will be summarized by study arm using descriptive statistics.
• Change in Patients' Global Impression of Change (PGIC) scale from baseline [360 days after intervention]: The Patient Global Impression of Change (PGIC) scale is a subjective measure used to evaluate a patient's perceived improvement following treatment, rated on a 7-point Likert scale ranging from 1 to 7 \[1= "No change (or condition has got worse)" to 7 = "a great deal better, and a considerable improvement that has made all the difference"\], wherein higher scores are associated with improved patient impression following treatment. Change from baseline scores will be summarized by study arm using descriptive statistics.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for participation:

* Subjects at least 18 years of age at Screening
* Primary complaint of axial low-back pain suggestive of bilateral facet joint involvement (i.e., facet mediated CLBP) by evidence of provocative testing (e.g., axial loading, paraspinal tenderness)
* Low back pain is chronic (i.e., ≥ 3 months' duration)
* Low back pain is moderate to severe (score of ≥ 5 to ≤ 9) on the 0 to 10 NRS at Screening
* Low back pain causes functional impairment (≥ 30% on ODI) at Screening
* Successful trial of two diagnostic medial branch blocks consisting of two positive blocks with local anesthetic only (i.e., no steroids) that results in at least 80% relief of primary (index) pain for the duration of the local anesthetic used
* Failure of at least three months of conservative non-operative therapy (e.g., physical therapy, chiropractic care, sleep hygiene, weight loss, spinal injections, NSAIDs, physician-directed exercise program or other appropriate analgesics)
* Able to provide informed consent, adhere to the study visit schedule, and complete all study assessment

Exclusion Criteria:

Subjects who meet any of the following exclusion criteria will not be eligible for participation in this study:

* Active workers' compensation, personal injury, Social Security disability insurance (SSDI), or other litigation/compensation related to the spine
* Serious spinal disorders (verified on magnetic resonance imaging (MRI)) that may impact outcomes, including any of the following:

  1. Suspected cauda equina syndrome (e.g., bowel/bladder dysfunction)
  2. Infection
  3. Tumor
  4. Traumatic fracture
  5. Systemic inflammatory spondyloarthropathy
  6. Lumbar radiculopathy/radiculitis (i.e., root irritation and deficit)
  7. Neurogenic claudication Prior lumbar spinal fusion surgery at the intended treatment levels
* Comorbidity that, in the judgment of the Investigator, may affect the subject's ability to participate in the study including lumbar radiculopathy and neuropathic pain disorder
* Currently pregnant, nursing, or planning to become pregnant during the study
* Known contraindication to study device, including any of the following:

  1. Cryoglobulinemia
  2. Paroxysmal cold hemoglobinuria
  3. Cold urticaria
  4. Raynaud's disease
  5. Open and/or infected wounds at or near the treatment site
  6. Coagulopathy
* Severe chronic pain disorder that in the opinion of the investigator may impact study outcomes
* Presence of any of the following:

  1. Spinal neurostimulator
  2. Intrathecal analgesic drug pump
  3. Cardiac implantable device
* Current manifestation of poorly controlled mental illness or catastrophizing that in the opinion of the investigator may meaningfully impact treatment outcomes, including any of the following:

  1. Mood disorder (e.g., depression, bipolar)

     Patient Health Questionnaire (PHQ-9) ≥ 12 at Screening
  2. Psychotic disorder (e.g., schizophrenia)
  3. Catastrophizing

Patient Catastrophizing Scale (PCS) score > 30 at Screening

* Subject received other spine intervention/therapies in the 30 days prior to block administration (e.g., spinal injections, minimally invasive therapies, surgical therapies) at the intended lumbar treatment levels
* Subject received radiofrequency ablation in the low back region ≤ 6 months before study enrollment at the intended lumbar treatment levels
* Pain relief following diagnostic medial branch blocks lasted longer than the duration of the local anesthetic used (i.e., > 24 hours)

  1. History, suspicion, or clinical manifestation of:
  2. Alcohol abuse or dependence
  3. Illicit drug use
* Opioid abuse or dependence (≥40 mg medication PO/day in past 30 days)
* Given the COVID-19 pandemic, the subject must be medically fit/cleared for surgery by the investigator. If there is a concern about a subject's recent or potential exposure to COVID-19, or if the subject is not medically fit/cleared for surgery due to suspected COVID-19 illness/symptoms (or other serious illness), the subject must be excluded.

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• Karina Gritsenko, MD, Principal investigator, Montefiore Medical Center