Sacroiliac Joint Fusion Comparison Study

Introduction This document is a protocol for a human research study. This study is to be conducted according to US and international standards of Good Clinical Practice (FDA Title 21 part 312 and International Conference on Harmonization guidelines), applicable government regulations and Institutional research policies and procedures.

Background

Sacroiliac joint (SIJ) dysfunction is a common pain condition involving the buttock and may irradiate in the low back, groin and/or lower extremity. About one in five patients with low back pain is estimated to have SI joint pain. The economic burden of SIJ pain is high in the United States and there is a need for more cost effective treatment options. There is a lack of relevant high quality studies that compared nonsurgical and surgical treatment for SI joint dysfunction.

Sacroiliac joint (SIJ) dysfunction has been estimated to be the origin of lower back pain in 13 to 30% of patients. SIJ pain is usually referred to the buttock, low back, groin and/or lower extremity. SIJ osteoarthritis, trauma, SIJ degeneration following lumbar fusion and postpartum SIJ dysfunction are common causes of SIJ pain found in a clinical setting. Other less common causes for SIJ pain include inflammatory sacroiliitis, infective sacroiliitis, insufficiency stress fractures and neoplasia.

Diagnostic evidences for SIJ dysfunction

The presenting symptoms of SIJ dysfunction can be similar to those of other spinal conditions such as disc herniation or degenerative spinal stenosis. Unlike radiculopathy, there is often an absence of specific radiological finding with SIJ dysfunction. A gold standard for SI joint pain diagnosis does not exist, but dual comparative local anesthetic joint blocks with at least 70% pain relief are considered a validated diagnostic test for SI joint pain. Reproducibility of SIJ pain with at least 3 SIJ-selective stressing tests, including the thigh trust, compression, Patrick's, distraction and Gaenslen's test, is also considered having good diagnostic validity.

Investigational Agents and Preclinical Data

Nonsurgical treatment efficacy for SIJ dysfunction

Sacroiliac dysfunction is thought to be secondary to a loss of SIJ stability caused by either deficient form closure (joint anatomy) or force closure (compressive forces exerted by neuromuscular and ligamentous structures around the joint. Physical therapy can improve SI joint pain by increasing force closure. Pelvic stabilization, strengthening and self-bracing exercises have been showed to improve force closure and may provide SIJ pain relief.

When SIJ pain fails to improve with physical therapy, several pain management interventions can be offered to patients. Up to now, the level of evidence for SIJ intraarticular or periarticular steroid injections is mainly limited to short-term outcome (3 months) and the effectiveness results are conflicting between different studies.

Compared to conventional radio frequency ablation, the effectiveness of cooled radiofrequency ablation is supported by superior level of evidence. Two randomized controlled trials comparing cooled radio frequency ablation vs placebo demonstrated a success rate varying between 38 to 57% at 6 months for cooled radiofrequency ablation. Observational studies also demonstrated success rate varying from 40% to 71% at 6 months for both conventional and cooled radio frequency ablation. The effectiveness of conventional and cooled radio frequency ablation at 9 and 12 months are more limited and some studies did report loss of effectiveness at 12 months. Based on the available data, there is no evidence supporting clinical superiority between traditional and cool radio frequency ablation. A retrospective study on 88 patients revealed comparable effectiveness between conventional and cool radio frequency ablation with > 50% pain reduction in the majority of patients after 3 and 6 months.

Surgical treatment evidence for SIJ dysfunction

Minimally invasive SIJ fusion is a surgical treatment aimed at stabilizing the SIJ to reduce pain, disability and improve quality of life. In a recent randomized controlled trial called Investigation of Sacroiliac Fusion Treatment (INSITE), minimally invasive SIJ fusion, using triangular titanium implants (iFuse Implant System, SI-BONE®, San Jose, CA), has been shown superior to non-surgical treatments in managing SIJ dysfunction at 6 months (81.4% vs 26.1% success rate) and the results in the surgical group were sustained at one year and two years of follow-up. In this trial, success rate was defined as a decreased in SIJ pain Visual Analogue Score of at least 20 mm compared to baseline, an absence of device-related serious adverse events, an absence of neurological worsening and no surgical reintervention. There were 101 subjects in the SIJ fusion group who completed the 6 months follow-up.

Clinical Data to Date The INSITE study is the first and only published Level 1 randomized controlled trial to have compared SIJ fusion with nonsurgical treatment. Although this study demonstrated prolonged improvement in pain, disability and quality of life with SIJ fusion, superiority of SIJ fusion compared to nonsurgical treatment at 6 months cannot be generalized. This superiority trial may not have been truly clinically relevant because there was no specific treatment protocol used in the nonsurgical group for each subject. Nonsurgical management consisted of physical therapy in 98%, at least one steroid injection in 74%, 2 steroid injections in 4% and radiofrequency ablation of the sacral nerve root lateral branches in 46% of the 46 subjects assigned to nonsurgical treatment. The different proportions of treatment offered in the nonsurgical group may in fact differ from other pain management clinical practices and the generalizability of the results is questionable.

Compared to all nonsurgical treatment available for SIJ pain, the effectiveness of radiofrequency ablation is supported by literature of higher level of evidence. Prolonged therapeutic effect up to 6 months after the procedure has been demonstrated for radiofrequency ablation. In the INSITE study, only 21 subjects received radio frequency ablation, a group size that corresponds to only 21% of the number of subjects studied for SIJ fusion. This may explain why the nonsurgical group only had 26.1% success rate in this trial. The quality of evidence for the INSITE study may also be contested as the study sponsor, SI-BONE®, participated in the manuscript redaction and performed the statistical analysis.

The costs of nonsurgical treatments for SIJ pain are substantial in the United Sates medicare population and there is a need to assess the best cost effective therapy for SI joint pain. SIJ fusion and RFN are two SIJ pain treatment modalities that have been studied with a higher level of evidence compared to other modalities, showing significant effectiveness lasting more than 6 months after each procedure. However the effectiveness and costs associated with these two different treatments have never been compared in a clinically relevant randomized trial.

Dose Rationale and Risk/Benefits

RISKS

General / Unforeseeable

The risks of receiving a SIJ fusion include but are not limited to:

• post-operative incisional pain or worsened pain due to muscle spams
• hematoma and/or surgical site infection (less likely)
• nerve damage that can cause paralysis, loss of sensation or pain (unlikely
• possible second intervention for revision or withdrawal of implants (unlikely)

The risks of receiving SIJ radiofrequency ablation include but are not limited to:

• Pain or discomfort around the area treated
• numbness of skin covering the area treated, worsened pain due to muscle spasm,
• permanent nerve pain (less likely)
• allergies or reactions to medications, infection and/or hematoma (less likely) 3rd degree burn (rare)
• Nerve damage due to trauma (rare)

Other risks that are not specifically related to SIJ fusion or SIJ radiofrequency ablation but may occur during any procedure include:

• cardiovascular and /or cerebrovascular events
• cardiac arrhythmia
• deep vein thrombosis
• pulmonary emboli
• pneumonia
• urinary tract infection
• skin abrasions
• coma or death

Radiation Risks

Fluoroscopy is an imaging technique that uses X-rays during the SIJ fusion or SIJ radiofrequency ablation. This form or ionizing radiation poses a potential for increasing the patient's risk of radiation-induced cancer. Radiations doses and exposure during the study are the same that would be used if the subjects were receiving the treatment outside of this study. Therefore, this study does not involve any additional radiation risk for the subjects.

Study Objectives

Primary objective: Determine clinical superiority between minimally invasive SIJ fusion and radiofrequency ablation in chronic SIJ dysfunction patients

Secondary Objectives: Compare cost-effectiveness between treatment groups

Study Design

General Design

• Randomized controlled trial where randomization is done by a random number generator. Even numbers will be directed to the SI joint procedure group and odd numbers will be directed to the radiofrequency ablation procedure.
• The enrolment uses a 1:1 ratio of SIJ fusion to radio frequency ablation
• The subjects and investigators are not blinded to treatment allocation

Subjects will have a detailed medical history and will complete these questionnaires

• SIJ pain rating using the Visual Analogue Scale (VAS)
• Oswestry Disability Index (ODI)
• Short Form-36 (SF-36)

All subjects will be evaluated at randomization and at follow-up visits scheduled at 1, 3, 6, 9, and 12 months.