Investigation of Sacroiliac Fusion Treatment (INSITE) (INSITE)

• ClinicalTrials.gov Identifier: NCT01681004
• Recruitment Status: Completed
• First Posted: September 7, 2012
• Results First Posted: August 25, 2017
• Last Update Posted: August 25, 2017
• Sponsor: SI-BONE, Inc.
• Information provided by (Responsible Party): SI-BONE, Inc.

Tracking Information

• First Submitted Date: September 1, 2012
• First Posted Date: September 7, 2012
• Results First Submitted Date: June 22, 2017
• Results First Posted Date: August 25, 2017
• Last Update Posted Date: August 25, 2017
• Study Start Date: September 2012
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 23, 2017)

Subject Success [ Time Frame: 6 months ]

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.

Original Primary Outcome Measures (submitted: September 6, 2012)

Subject Success [ Time Frame: 6 months ]

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.

Current Secondary Outcome Measures (submitted: August 23, 2017)

• Improvement in SI Joint Pain VAS Score at 1 Month [ Time Frame: 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.
• Improvement in Si Joint Pain VAS Score at 3 Months [ Time Frame: 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.
• Improvement in SI Joint Pain VAS Score at 6 Months [ Time Frame: 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.
• Improvement in SI Joint Pain VAS Score at 12 Months [ Time Frame: 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.
• Improvement in SI Joint Pain VAS Score at 24 Months [ Time Frame: 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.
• Improvement in Back Dysfunction [ Time Frame: 1 month ]
  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.
• Improvement in Back Dysfunction [ Time Frame: 3 Months ]
  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.
• Improvement in Back Dysfunction [ Time Frame: 6 Months ]
  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.
• Improvement in Back Dysfunction [ Time Frame: 12 Months ]
  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.
• Improvement in Back Dysfunction [ Time Frame: 24 Months ]
  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.
• Improvement in Quality of Life (QOL) as Measured by SF-36 PCS (Physical Component) at Post-operative Visits [ Time Frame: 6 months ]
  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.
• Improvement in Quality of Life (QOL) as Measured by SF-36 PCS (Physical Component) at Post-operative Visits [ Time Frame: 12 Months ]
  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.
• Improvement in Quality of Life (QOL) as Measured by SF-36 PCS (Physical Component) at Post-operative Visits [ Time Frame: 24 months ]
  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.
• Improvement in Quality of Life (QOL) as Measured by EQ-5D (EuroQol-5D) at Post-operative Visits [ Time Frame: 6 months ]
  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.
• Improvement in Quality of Life (QOL) as Measured by EQ-5D (EuroQol-5D) at Post-operative Visits [ Time Frame: 12 Months ]
  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.
• Improvement in Quality of Life (QOL) as Measured by EQ-5D (EuroQol-5D) at Post-operative Visits [ Time Frame: 24 months ]
  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.
• Ambulatory Status [ Time Frame: 24 months (surgical group), 6 months (non-surgical group) ]
  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.
• Work Status [ Time Frame: 1 month ]
  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.
• Work Status [ Time Frame: 3 Months ]
  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.
• Work Status [ Time Frame: 6 Months ]
  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.
• Work Status [ Time Frame: 12 Months ]
  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.
• Work Status [ Time Frame: 18 Months ]
  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.
• Work Status [ Time Frame: 24 Months ]
  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.
• Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Procedure, discharge, 1, 3, 6, 12, 18 and 24 months ]
  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.

Original Secondary Outcome Measures (submitted: September 6, 2012)

• Improvement in Si joint pain [ Time Frame: Screening, 1, 3, 6, 12, 18 and 24 months ]
  Improvement in SI joint pain VAS score at post-operative visits
• Improvement in back dysfunction [ Time Frame: Screening, 1, 3, 6, 12 and 24 months ]
  Improvement in ODI at post-operative visits
• Improvement in quality of life [ Time Frame: Baseline, 6, 12 and 24 months ]
  Improvement in QOL as measured by SF-36 PCS and ED-5D at post-operative visits
• Ambulatory status [ Time Frame: Baseline, 1,3,6,12,18 and 24 months ]
  Time to full ambulation amongst those without full ambulation at baseline
• Work status [ Time Frame: Baseline, 1,3,6,12,18 and 24 months ]
  Proportion of non-working subjects who return to work
• Serious adverse events [ Time Frame: Procedure, discharge, 1, 3, 6, 12, 18 and 24 months ]
  Any event meeting ISO14155 definition for serious adverse event at following timepoints: 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Investigation of Sacroiliac Fusion Treatment (INSITE)
• Official Title: INSITE Investigation of Sacroiliac Fusion Treatment
• Brief Summary: 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: 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.
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Parallel group randomized controlled trial

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Degenerative Sacroiliitis
• Sacroiliac Joint Disruption

Intervention

• Device: iFuse Implant System
  Placement of iFuse implant system via surgery
• Other: Non-surgical management
  Medications for pain, physical therapy, SI joint injection and RF ablation

Study Arms

• Experimental: iFuse Implant System
  Surgical placement of iFuse implants in the affected SI joint
  Intervention: Device: iFuse Implant System
• Active Comparator: Non-Surgical Management
  Medications, SI joint injection, physical therapy and RF ablation of SI joint
  Intervention: Other: Non-surgical management

Publications *

• Polly DW, Swofford J, Whang PG, Frank CJ, Glaser JA, Limoni RP, Cher DJ, Wine KD, Sembrano JN; INSITE Study Group. Two-Year Outcomes from a Randomized Controlled Trial of Minimally Invasive Sacroiliac Joint Fusion vs. Non-Surgical Management for Sacroiliac Joint Dysfunction. Int J Spine Surg. 2016 Aug 23;10:28. doi: 10.14444/3028. eCollection 2016.
• Polly D, Cher D, Whang PG, Frank C, Sembrano J; INSITE Study Group. Does Level of Response to SI Joint Block Predict Response to SI Joint Fusion? Int J Spine Surg. 2016 Jan 21;10:4. doi: 10.14444/3004. eCollection 2016.
• Cher DJ, Frasco MA, Arnold RJ, Polly DW. Cost-effectiveness of minimally invasive sacroiliac joint fusion. Clinicoecon Outcomes Res. 2015 Dec 18;8:1-14. doi: 10.2147/CEOR.S94266. eCollection 2016. Erratum In: Clinicoecon Outcomes Res. 2016;8:305.
• Polly DW, Cher DJ, Wine KD, Whang PG, Frank CJ, Harvey CF, Lockstadt H, Glaser JA, Limoni RP, Sembrano JN; INSITE Study Group. Randomized Controlled Trial of Minimally Invasive Sacroiliac Joint Fusion Using Triangular Titanium Implants vs Nonsurgical Management for Sacroiliac Joint Dysfunction: 12-Month Outcomes. Neurosurgery. 2015 Nov;77(5):674-90; discussion 690-1. doi: 10.1227/NEU.0000000000000988.
• Whang P, Cher D, Polly D, Frank C, Lockstadt H, Glaser J, Limoni R, Sembrano J. Sacroiliac Joint Fusion Using Triangular Titanium Implants vs. Non-Surgical Management: Six-Month Outcomes from a Prospective Randomized Controlled Trial. Int J Spine Surg. 2015 Mar 5;9:6. doi: 10.14444/2006. eCollection 2015.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 23, 2017): 159
• Original Estimated Enrollment (submitted: September 6, 2012): 200
• Actual Study Completion Date: June 2017
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age 21-70 at time of screening
2. Patient has lower back pain for >6 months inadequately responsive to conservative care

3. Diagnosis of sacroiliac joint disruption or degenerative sacroiliitis based on ALL of the following:

   1. 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
   2. Patient has at least 3 of 5 physical examination maneuvers specific for the SI joint (see Table 3), and
   3. 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
   4. 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
4. Baseline Oswestry Disability Index (ODI) score of at least 30%
5. Baseline SI joint pain score of at least 50 on 0-100 mm visual analog scale*
6. Patient has signed study-specific informed consent form
7. Patient has the necessary mental capacity to participate and is physically able to comply with study protocol requirements

Exclusion Criteria:

1. 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**

2. Other known sacroiliac pathology such as:

   1. Sacral dysplasia
   2. Inflammatory sacroiliitis (e.g., ankylosing spondylitis or other HLA-associated spondyloarthropathy)
   3. Tumor
   4. Infection
   5. Acute fracture
   6. Crystal arthropathy
3. History of recent (<1 year) major trauma to pelvis
4. 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.
5. Osteomalacia or other metabolic bone disease
6. Chronic rheumatologic condition (e.g., rheumatoid arthritis)
7. Any condition or anatomy that makes treatment with the iFuse Implant System infeasible
8. Chondropathy
9. Known allergy to titanium or titanium alloys
10. Use of medications known to have detrimental effects on bone quality and soft-tissue healing
11. Prominent neurologic condition that would interfere with physical therapy
12. Current local or systemic infection that raises the risk of surgery
13. Patient currently receiving or seeking worker's compensation, disability remuneration, and/or involved in injury litigation.
14. Currently pregnant or planning pregnancy in the next 2 years
15. Patient is a prisoner or a ward of the state.
16. Known or suspected drug or alcohol abuse***
17. Diagnosed psychiatric disease (e.g., schizophrenia, major depression, personality disorders) that could interfere with study participation
18. Patient is participating in an investigational study or has been involved in an investigational study within 3 months prior to evaluation for participation

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01681004
• Other Study ID Numbers: 300103
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: SI-BONE, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: SI-BONE, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Daniel J Cher, MD; SI-BONE

• PRS Account: SI-BONE, Inc.
• Verification Date: August 2017