Investigation of Sacroiliac Fusion Treatment (INSITE)

Study Overview
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Brief Summary
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The purpose of this study is to compare outcomes when patients with degenerative sacroiliitis (arthritis of the SI joint) and or sacroiliac disruption (abnormal separation or tearing of the sacroiliac joint)undergo either SI joint fusion with the iFuse Implant System or undergo specific, targeted non-surgical treatment of the SI joint.

Detailed Description
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The intended analysis was to examine differences in responses at 6 months. It was acknowledged that subjects with chronic pain in the NSM arm group might not experience any benefit as there was little evidence at the time that NSM was helpful. The protocol included optional crossover to other treatments, including surgical treatment. The protocol anticipated a high crossover rate and therefore did not include any comparative analyses after month 6.

Official Title
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INSITE Investigation of Sacroiliac Fusion Treatment

Conditions
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Degenerative Sacroiliitis, Sacroiliac Joint Disruption

Intervention / Treatment
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* Device: iFuse Implant System
* Other: Non-surgical management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 21-70 at time of screening Patient has lower back pain for >6 months inadequately responsive to conservative care Diagnosis of sacroiliac joint disruption or degenerative sacroiliitis based on ALL of the following: Patient has pain at or close to the posterior superior iliac spine (PSIS) with possible radiation into buttocks, posterior thigh or groin and can point with a single finger to the location of pain (Fortin Finger Test), and Patient has at least 3 of 5 physical examination maneuvers specific for the SI joint (see Table 3), and Patient has improvement in lower back pain numeric rating scale (NRS) of at least 50% after injection of local anesthetic into affected SI joint(s) (see Section 3.6.4), and One or more of the following: i. SI joint disruption: Asymmetric SI joint widening on X-ray or CT scan, or Leakage of contrast on diagnostic arthrography ii. Degenerative sacroiliitis: Radiographic evidence of SI joint degeneration, including sclerosis, osteophytes, subchondral cysts, or vacuum phenomenon on CT or plain film, or Due to prior lumbosacral spine fusion Baseline Oswestry Disability Index (ODI) score of at least 30% Baseline SI joint pain score of at least 50 on 0-100 mm visual analog scale* Patient has signed study-specific informed consent form Patient has the necessary mental capacity to participate and is physically able to comply with study protocol requirements Exclusion Criteria: Severe back pain due to other causes, such as lumbar disc degeneration, lumbar disc herniation, lumbar spondylolisthesis, lumbar spinal stenosis, lumbar facet degeneration, and lumbar vertebral body fracture** Other known sacroiliac pathology such as: Sacral dysplasia Inflammatory sacroiliitis (e.g., ankylosing spondylitis or other HLA-associated spondyloarthropathy) Tumor Infection Acute fracture Crystal arthropathy History of recent (<1 year) major trauma to pelvis Previously diagnosed osteoporosis (defined as prior T-score <-2.5 or history of osteoporotic fracture). Patients meeting the osteoporosis screening criteria identified by the National Osteoporosis Foundation should be screened for osteoporosis with DEXA.**** See Section 3.6.4. Osteomalacia or other metabolic bone disease Chronic rheumatologic condition (e.g., rheumatoid arthritis) Any condition or anatomy that makes treatment with the iFuse Implant System infeasible Chondropathy Known allergy to titanium or titanium alloys Use of medications known to have detrimental effects on bone quality and soft-tissue healing Prominent neurologic condition that would interfere with physical therapy Current local or systemic infection that raises the risk of surgery Patient currently receiving or seeking worker's compensation, disability remuneration, and/or involved in injury litigation. Currently pregnant or planning pregnancy in the next 2 years Patient is a prisoner or a ward of the state. Known or suspected drug or alcohol abuse*** Diagnosed psychiatric disease (e.g., schizophrenia, major depression, personality disorders) that could interfere with study participation Patient is participating in an investigational study or has been involved in an investigational study within 3 months prior to evaluation for participation

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel group randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: iFuse Implant System<br>Surgical placement of iFuse implants in the affected SI joint | Device: iFuse Implant System<br>* Placement of iFuse implant system via surgery<br>|
| Active Comparator: Non-Surgical Management<br>Medications, SI joint injection, physical therapy and RF ablation of SI joint | Other: Non-surgical management<br>* Medications for pain, physical therapy, SI joint injection and RF ablation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject Success | Composite endpoint of reduction from baseline in VAS back pain score by at least 20 mm, lack of device-related serious adverse events, absence of neurologic worsening and absence of surgical re-intervention. Note that the primary endpoint analysis is **intent to treat**, meaning that an outcome (success or failure) is assigned to all subjects randomized and treated. Subjects who withdrew early were deemed study failures. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in SI Joint Pain VAS Score at 1 Month | Improvement in SI joint pain VAS score of greater than or equal to 20 points, at post-operative & NSM visit after 1 month. The Visual Analog Scale (VAS) is a 100 mm line on which the subject indicates their level of pain. 0 = no pain. 100 = worst imaginable pain. Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 1 month | 
| Improvement in Si Joint Pain VAS Score at 3 Months | Improvement in SI joint pain VAS score of greater than or equal to 20 points, at post-operative & NSM visits after 3 months. The Visual Analog Scale (VAS) is a 100 mm line on which the subject indicates their level of pain. 0 = no pain. 100 = worst imaginable pain. Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 3 Months | 
| Improvement in SI Joint Pain VAS Score at 6 Months | Improvement in SI joint pain VAS score of greater than or equal to 20 points, at post-operative & NSM visits after 6 months. The Visual Analog Scale (VAS) is a 100 mm line on which the subject indicates their level of pain. 0 = no pain. 100 = worst imaginable pain. Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 6 Months | 
| Improvement in SI Joint Pain VAS Score at 12 Months | Improvement in SI joint pain VAS score of greater than or equal to 20 points compared to baseline. The Visual Analog Scale (VAS) is a 100 mm line on which the subject indicates their level of pain. 0 = no pain. 100 = worst imaginable pain. Note that secondary endpoint analysis is based on available data only. Subjects in the NSM group who crossed over are considered failures for this endpoint by definition. | 12 Months | 
| Improvement in SI Joint Pain VAS Score at 24 Months | Improvement in SI joint pain VAS score of greater than or equal to 20 points compared to baseline. The Visual Analog Scale (VAS) is a 100 mm line on which the subject indicates their level of pain. 0 = no pain. 100 = worst imaginable pain. Note that secondary endpoint analysis is based on available data only. Subjects in the NSM group who crossed over are considered failures for this endpoint by definition. | 24 Months | 
| Improvement in Back Dysfunction | Improvement in ODI score of greater than or equal to 15 points, at month 1. Oswestry Disability Index is a validated measure of disability related to low back pain. There are 10 sections, each with a score between 0-5. Scores are expressed on a percent basis without using the percent term. Scores range from 0 (no disability) to 100 (completely disabled). Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 1 month | 
| Improvement in Back Dysfunction | Improvement in ODI score of greater than or equal to 15 points, at month 3. Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 3 Months | 
| Improvement in Back Dysfunction | Improvement in ODI score of greater than or equal to 15 points, at post-operative visits. 6 month visit. Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 6 Months | 
| Improvement in Back Dysfunction | Improvement in ODI score of greater than or equal to 15 points compared to baseline. Oswestry Disability Index is a validated measure of disability related to low back pain. Subjects in the NSM group who crossed over are considered failures for this endpoint by definition. | 12 Months | 
| Improvement in Back Dysfunction | Improvement in ODI score of greater than or equal to 15 points compared to baseline. Oswestry Disability Index is a validated measure of disability related to low back pain. Subjects in the NSM group who crossed over are considered failures for this endpoint by definition. | 24 Months | 
| Improvement in Quality of Life (QOL) as Measured by SF-36 PCS (Physical Component) at Post-operative Visits | Improvement in quality of life (QOL) as measured by SF-36 PCS (Physical Component) at post-operative / NSM visits. The Short Form 36 health survey (SF-36) is a 36-item patient reported health questionnaire to measure quality of life across 8 domains. The PCS is the Physical Component Summary score. PCS is normed, so that normal scores are 50 +- 10. Higher scores indicate higher quality of life; lower scores indicate lower quality of life. SF-36 PCS (NBS, 2009 norms) ranges from 5 (minimum value, poor physical function) to 80 (maximum, excellent clinical function). Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 6 months | 
| Improvement in Quality of Life (QOL) as Measured by SF-36 PCS (Physical Component) at Post-operative Visits | Improvement in quality of life (QOL) as measured by SF-36 PCS (Physical Component) at post-operative / NSM visits. The Short Form 36 health survey (SF-36) is a 36-item patient reported health questionnaire to measure quality of life across 8 domains. The PCS is the Physical Component Summary score. PCS is normed, so that normal scores are 50 +- 10. Higher scores indicate higher quality of life; lower scores indicate lower quality of life. SF-36 PCS (NBS, 2009 norms) ranges from 5 (minimum value, poor physical function) to 80 (maximum, excellent clinical function). Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 12 Months | 
| Improvement in Quality of Life (QOL) as Measured by SF-36 PCS (Physical Component) at Post-operative Visits | Improvement in quality of life (QOL) as measured by SF-36 PCS (Physical Component) at post-operative / NSM visits. The Short Form 36 health survey (SF-36) is a 36-item patient reported health questionnaire to measure quality of life across 8 domains. The PCS is the Physical Component Summary score. PCS is normed, so that normal scores are 50 +- 10. Higher scores indicate higher quality of life; lower scores indicate lower quality of life. SF-36 PCS (NBS, 2009 norms) ranges from 5 (minimum value, poor physical function) to 80 (maximum, excellent clinical function). Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 24 months | 
| Improvement in Quality of Life (QOL) as Measured by EQ-5D (EuroQol-5D) at Post-operative Visits | Improvement in quality of life (QOL) as measured by EQ-5D (EuroQol-5D) at post-operative visits. EQ-5D is a five-question broad quality of life measure that can be combined into a single index and represents the time trade-off (TTO) utility of current health. A score of 0 would = worst imaginable health, while a score of 1.0 would be best imaginable health. Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 6 months | 
| Improvement in Quality of Life (QOL) as Measured by EQ-5D (EuroQol-5D) at Post-operative Visits | Improvement in quality of life (QOL) as measured by EQ-5D (EuroQol-5D) at post-operative visits. EQ-5D is a five-question broad quality of life measure that can be combined into a single index and represents the time trade-off (TTO) utility of current health. A score of 0 would = worst imaginable health, while a score of 1.0 would be best imaginable health. Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 12 Months | 
| Improvement in Quality of Life (QOL) as Measured by EQ-5D (EuroQol-5D) at Post-operative Visits | Improvement in quality of life (QOL) as measured by EQ-5D (EuroQol-5D) at post-operative visits. EQ-5D is a five-question broad quality of life measure that can be combined into a single index and represents the time trade-off (TTO) utility of current health. A score of 0 would = worst imaginable health, while a score of 1.0 would be best imaginable health. Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 24 months | 
| Ambulatory Status | Time to full ambulation among those without full ambulation at baseline. 60 days was the median of time to full ambulation for the iFuse implant System arm. | 24 months (surgical group), 6 months (non-surgical group) | 
| Work Status | Proportion of non-working (due to back pain or other reasons) subjects who return to work Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 1 month | 
| Work Status | Non-working subjects (due to back pain or other reasons) who return to work Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 3 Months | 
| Work Status | Non-working subjects who return to work Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 6 Months | 
| Work Status | Non-working subjects who return to work Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 12 Months | 
| Work Status | Non-working subjects who return to work Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 18 Months | 
| Work Status | Non-working subjects who return to work Note that secondary endpoint analysis is based on available data only. No imputation of missing scores was prespecified in the protocol. | 24 Months | 
| Number of Participants With Serious Adverse Events (SAEs) | Any event meeting ISO 14155 definition for serious adverse event at following time points: during procedure (if randomized to iFuse), hospital discharge (if iFuse, typically 1-2 days), and 1, 3, 6, 12, 18 and 24 months after randomization. | Procedure, discharge, 1, 3, 6, 12, 18 and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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si joint injury, si joint pain, sacroiliac joint arthritis treatment, si joint, si joint treatment, si joint injections, si joint inflammation, si joint problems, si joint symptoms, hypermobile si joint, si joint arthritis, si joint pain treatment, inflamed si joint, si joint sclerosis, locked si joint, si joint injuries, si joint disease, si joint infection, sacroiliac joint pelvic pain