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

A Prospective, Randomized, Assessor Blind, Active-controlled, Single-center Study to Evaluate the Efficacy of Iovera Lumbar Medial Branch Cryoneurolysis Versus Radiofrequency Ablation for the Treatment of Facet-mediated Chronic Low Back Pain

A research study is being conducted to compare two treatments for long-term low back pain:

• One uses the iovera° system, which applies cold to certain nerves in the lower back.
• The other is the standard treatment called radiofrequency ablation, which uses heat.

The primary objective is to find out which treatment works better to reduce back pain. Participants in this study will be randomly placed in one of the two treatment groups. The clinical research team will check on participant pain levels and overall health before and after the procedure for about 12 months. The entire study will last about 14 months for each participant.

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.

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.