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.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Degenerative Sacroiliitis; Sacroiliac Joint Disruption
• Interventions: Device: iFuse Implant System; Other: Non-surgical management
• Enrollment: 159

Participant Flow

Recruitment Details
Pre-assignment Details	Of the 442 patients who were screened for participation at 19 sites, 159 (37.8%) were enrolled. Eleven subjects withdrew before treatment (1 before randomization and 10 after randomization but before any treatment was performed), yielding a total of 148 subjects who were enrolled, randomized and treated.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	Medications, SI joint injection, physical therapy and RF ablation of SI joint Non-surgical management: Medications for pain, physical therapy, SI joint injection and RF ablation. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Period Title: Primary Endpoint: 6 Months
Started	102	46
Crossover to Surgical Treatment	0	39 [1]
Completed	101	44
Not Completed	1	2
Reason Not Completed
Withdrawal by Subject	1	2
[1] Crossover to surgical treatment allowed per study protocol after the 6-month visit was complete.
Period Title: Study Completion
Started	101	44
Completed	89	36
Not Completed	12	8
Reason Not Completed
Lost to Follow-up	8	3
Physician Decision	1	3
Site Termination	2	1
Death	1	1

Baseline Characteristics

Arm/Group Title		iFuse Implant System	Non-Surgical Management	Total
Arm/Group Description		Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	Medications, SI joint injection, physical therapy and RF ablation of SI joint Non-surgical management: Medications for pain, physical therapy, SI joint injection and RF ablation Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.	Total of all reporting groups
Overall Number of Baseline Participants		102	46	148
Baseline Analysis Population Description		Of the 442 patients who were screened for participation at 19 sites, 159 (37.8%) were enrolled. Eleven subjects withdrew before treatment (1 before randomization and 10 after randomization but before any treatment was performed), yielding a total of 148 subjects who were enrolled, randomized and treated (102 to iFuse Implant System & 46 to NSM).
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	102 participants	46 participants	148 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	92 90.2%	38 82.6%	130 87.8%
	>=65 years	10 9.8%	8 17.4%	18 12.2%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	102 participants	46 participants	148 participants
	Female	75 73.5%	28 60.9%	103 69.6%
	Male	27 26.5%	18 39.1%	45 30.4%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	102 participants	46 participants	148 participants
White		97 95.1%	44 95.7%	141 95.3%
Black		3 2.9%	2 4.3%	5 3.4%
American Indian		1 1.0%	0 0.0%	1 0.7%
Other		1 1.0%	0 0.0%	1 0.7%
Ethnicity: Hispanic or Latino		4 3.9%	4 8.7%	8 5.4%
Body Mass Index, mean (range); Mean (Full Range); Unit of measure: Kg / m2
	Number Analyzed	102 participants	46 participants	148 participants
		30.4; (16.7 to 49.5)	30.6; (19.4 to 48.9)	30.43; (16.7 to 49.5)
Smoking Status (n, %); Measure Type: Number; Unit of measure: Participants	Number Analyzed	102 participants	46 participants	148 participants
Current Smoker		26	3	29
Former Smoker		30	13	43
Never smoker		46	30	76
Ambulatory without assistance; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	102 participants	46 participants	148 participants
		89 87.3%	41 89.1%	130 87.8%
Work status (n, %); Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	102 participants	46 participants	148 participants
Working full time		45 44.1%	21 45.7%	66 44.6%
Working part time		9 8.8%	4 8.7%	13 8.8%
Not working, student		1 1.0%	0 0.0%	1 0.7%
Not working, retired		21 20.6%	9 19.6%	30 20.3%
Not working due to back pain		20 19.6%	8 17.4%	28 18.9%
Not working other reason		6 5.9%	4 8.7%	10 6.8%
Prior Lumbar fusion (n, %); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	102 participants	46 participants	148 participants
		41 40.2%	17 37.0%	58 39.2%
Underlying diagnosis; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	102 participants	46 participants	148 participants
Degenerative sacroiliitis		88 86.3%	40 87.0%	128 86.5%
Sacroiliac joint disruption		14 13.7%	6 13.0%	20 13.5%
Years of pain, mean (range); Mean (Full Range); Unit of measure: Years
	Number Analyzed	102 participants	46 participants	148 participants
		7.0; (0.5 to 40.7)	5.0; (0.5 to 38.9)	6.0; (0.5 to 40.7)
Pain Syndrome; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	102 participants	46 participants	148 participants
Pain began peripartum		29 28.4%	19 41.3%	48 32.4%
Pain radiates down leg		89 87.3%	41 89.1%	130 87.8%
Groin pain		60 58.8%	29 63.0%	89 60.1%
Pain worse with sitting		89 87.3%	41 89.1%	130 87.8%
Pain worse with rising		88 86.3%	41 89.1%	129 87.2%
Pain worse with walking		87 85.3%	42 91.3%	129 87.2%
Pain worse with climbing stairs		93 91.2%	41 89.1%	134 90.5%
Pain worse with descending stairs		82 80.4%	37 80.4%	119 80.4%
Prior treatments; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	102 participants	46 participants	148 participants
Physical therapy		71 69.6%	36 78.3%	107 72.3%
Steroid SIJ injection		85 83.3%	42 91.3%	127 85.8%
RF ablation		21 20.6%	4 8.7%	25 16.9%
Taking opiods; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	102 participants	46 participants	148 participants
		70 68.6%	29 63.0%	99 66.9%
Participants with lumbar stenosis; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	102 participants	46 participants	148 participants
		15 14.7%	7 15.2%	22 14.9%
Participants with hip diagnosis (n, %); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	102 participants	46 participants	148 participants
		16 15.7%	3 6.5%	19 12.8%
Participants with sacral trauma (n, %); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	102 participants	46 participants	148 participants
		8 7.8%	3 6.5%	11 7.4%
VAS SIJ pain score, mean [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	102 participants	46 participants	148 participants
		82.3 (11.9)	82.2 (9.9)	82.3 (11.3)
		[1] Measure Description: The Visual Analog Scale (VAS) is a 100 mm line on which the subjects mark their pain rating. 0= no pain and 100= worst pain imaginable.
ODI score, mean [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	102 participants	46 participants	148 participants
		57.2 (12.8)	56.0 (14.0)	56.8 (13.2)
		[1] Measure Description: 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. If all sections are answered, the total possible score is 50/50 = 100% which is the worst disability possible on the scale. (0/50 = no disability at all.) If any section is skipped by the study participant, the total possible score for that section is removed from the denominator. Example - section 8 skipped, total possible score is 45/45 = 100%.
SF-36, mean [1]; Mean (Standard Deviation); Unit of measure: Units on a scale	Number Analyzed	102 participants	46 participants	148 participants
Physical component summary (PCS)		30.2 (6.2)	30.8 (6.2)	30.4 (6.2)
Mental component summary (MCS)		43.0 (11.5)	43.3 (12.1)	43.1 (11.6)
		[1] Measure Description: 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. 0% would represent the lowest or worst possible level of functioning while 100% would represent the highest / best possible level of functioning. The MCS is the Mental Component Summary score. 0% would represent the lowest or worst possible level of functioning while 100% would represent the highest / best possible level of functioning.
EQ-5D [1]; Mean (Standard Deviation); Unit of measure: Units on a scale	Number Analyzed	102 participants	46 participants	148 participants
Time trade-off (TTO) score		0.44 (0.18)	0.47 (0.19)	0.45 (0.18)
Health Thermometer		53.2 (23.8)	57.8 (22.9)	54.6 (23.5)
		[1] Measure Description: EQ-5D is a five-question broad quality of life measure that is combined into a single index using population norm data called 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. (Scores <0 are also possible, representing states worse than death.) EQ-5D also includes a 0-100 mm health thermometer, where 0 means death and 100 means perfect health.

Outcome Measures

1. Primary Outcome

Title	Subject Success
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

A modified intent-to-treat approach was used.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM with reporting to 6 months only. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	102	46
Measure Type: Count of Participants; Unit of Measure: Participants
	84 82.4%	12 26.1%

2. Secondary Outcome

Title	Improvement in SI Joint Pain VAS Score at 1 Month
Description	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.
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

2 iFuse and 1 NSM subjects did not complete the pain score.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	100	45
Measure Type: Count of Participants; Unit of Measure: Participants
	84 84.0%	13 28.9%

3. Secondary Outcome

Title	Improvement in Si Joint Pain VAS Score at 3 Months
Description	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.
Time Frame	3 Months

Outcome Measure Data

Analysis Population Description

2 iFuse and 3 NSM subjects did not complete the 3-month pain score.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	100	43
Measure Type: Count of Participants; Unit of Measure: Participants
	87 87.0%	17 39.5%

4. Secondary Outcome

Title	Improvement in SI Joint Pain VAS Score at 6 Months
Description	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.
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

1 iFuse and 3 NSM subjects did not complete the 6-month pain score.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	101	43
Measure Type: Count of Participants; Unit of Measure: Participants
	84 83.2%	12 27.9%

5. Secondary Outcome

Title	Improvement in SI Joint Pain VAS Score at 12 Months
Description	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.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

2 iFuse subjects did not complete the 12-month pain score. Analysis of 12-month scores in the NSM group is not valid because of the high crossover rate.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	100	6
Measure Type: Count of Participants; Unit of Measure: Participants
	81 81.0%	NA [1]

[1]

The intended analysis was to examine differences in responses at 6 months. The protocol anticipated a high crossover rate and therefore did not include any comparative analyses after month 6.

6. Secondary Outcome

Title	Improvement in SI Joint Pain VAS Score at 24 Months
Description	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.
Time Frame	24 Months

Outcome Measure Data

Analysis Population Description

12 iFuse subjects did not complete the 24-month pain score. Analysis of 24-month scores in the NSM group is not valid because of the high crossover rate.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	90	5
Measure Type: Count of Participants; Unit of Measure: Participants
	75 83.3%	NA [1]

[1]

The intended analysis was to examine differences in responses at 6 months. The protocol anticipated a high crossover rate and therefore did not include any comparative analyses after month 6.

7. Secondary Outcome

Title	Improvement in Back Dysfunction
Description	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.
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

2 iFuse and 1 NSM subjects did not complete ODI at 1 month

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	100	45
Measure Type: Count of Participants; Unit of Measure: Participants
	49 49.0%	6 13.3%

8. Secondary Outcome

Title	Improvement in Back Dysfunction
Description	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.
Time Frame	3 Months

Outcome Measure Data

Analysis Population Description

2 iFuse subjects and 3 NSM subjects did not complete ODI at month 3.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	100	43
Measure Type: Count of Participants; Unit of Measure: Participants
	72 72.0%	13 30.2%

9. Secondary Outcome

Title	Improvement in Back Dysfunction
Description	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.
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

1 iFuse and 2 NSM subjects did not complete ODI at month 6.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	101	44
Measure Type: Count of Participants; Unit of Measure: Participants
	74 73.3%	6 13.6%

10. Secondary Outcome

Title	Improvement in Back Dysfunction
Description	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.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

2 iFuse subjects did not complete ODI at month 12. ODI analysis is not valid in NSM group at 12 months because of high crossover.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	100	6
Measure Type: Count of Participants; Unit of Measure: Participants
	72 72.0%	NA [1]

[1]

The intended analysis was to examine differences in responses at 6 months. The protocol anticipated a high crossover rate and therefore did not include any comparative analyses after month 6.

11. Secondary Outcome

Title	Improvement in Back Dysfunction
Description	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.
Time Frame	24 Months

Outcome Measure Data

Analysis Population Description

The Count of participants = number of subjects that had a threshold change in ODI score of greater than or equal to 15 points. Overall number of participants = number of subjects analyzed. Of the 102, a total of 13 iFuse Implant subjects exited the study and 1 did not complete the ODI survey. By 6 months, 39 NSM subjects crossed over to surgical.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	88	40
Measure Type: Count of Participants; Unit of Measure: Participants
	60 68.2%	NA [1]

[1]

The intended analysis was to examine differences in responses at 6 months. The protocol anticipated a high crossover rate and therefore did not include any comparative analyses after month 6.

12. Secondary Outcome

Title	Improvement in Quality of Life (QOL) as Measured by SF-36 PCS (Physical Component) at Post-operative Visits
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

2 iFuse and 2 NSM subjects did not complete SF-36 at month 6.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	100	44
Mean (Standard Deviation); Unit of Measure: units on a scale
	12.5 (10.5)	1.3 (8.2)

13. Secondary Outcome

Title	Improvement in Quality of Life (QOL) as Measured by SF-36 PCS (Physical Component) at Post-operative Visits
Description	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.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

A total of 2 iFuse subjects had exited the study before making it to their 12 month visit. This outcome is not evaluated in the NSM group at month 12 because high crossover to surgical treatment prevents valid analysis.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	100	6
Mean (Standard Deviation); Unit of Measure: units on a scale
	13.0 (9.9)	NA [1] (NA)

[1]

The intended analysis was to examine differences in responses at 6 months. The protocol anticipated a high crossover rate and therefore did not include any comparative analyses after month 6.

14. Secondary Outcome

Title	Improvement in Quality of Life (QOL) as Measured by SF-36 PCS (Physical Component) at Post-operative Visits
Description	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.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Change in QOL score at 24 months. 89 participants had QOL information at 24 months. Analysis of the NSM cohort is not done because high crossover to surgery prevents valid analysis.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	89	5
Mean (Standard Deviation); Unit of Measure: units on a scale
	11.2 (10.7)	NA [1] (NA)

[1]

The intended analysis was to examine differences in responses at 6 months. The protocol anticipated a high crossover rate and therefore did not include any comparative analyses after month 6.

15. Secondary Outcome

Title	Improvement in Quality of Life (QOL) as Measured by EQ-5D (EuroQol-5D) at Post-operative Visits
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Results show improvement in score from baseline.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	100	44
Mean (Standard Deviation); Unit of Measure: units on a scale
	0.29 (0.22)	0.06 (0.28)

16. Secondary Outcome

Title	Improvement in Quality of Life (QOL) as Measured by EQ-5D (EuroQol-5D) at Post-operative Visits
Description	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.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

2 iFuse subjects did not complete the survey at month 12. Due to high crossover rate to surgery, analysis in the NSM group is not valid.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	100	6
Mean (Standard Deviation); Unit of Measure: units on a scale
	0.31 (0.22)	NA [1] (NA)

[1]

The intended analysis was to examine differences in responses at 6 months. The protocol anticipated a high crossover rate and therefore did not include any comparative analyses after month 6.

17. Secondary Outcome

Title	Improvement in Quality of Life (QOL) as Measured by EQ-5D (EuroQol-5D) at Post-operative Visits
Description	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.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

13 iFuse subjects did not complete the 24-month assessment. Analysis was not done for the NSM group at 24 months due to the high crossover rate.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	89	5
Mean (Standard Deviation); Unit of Measure: units on a scale
	0.29 (0.24)	NA [1] (NA)

[1]

The intended analysis was to examine differences in responses at 6 months. The protocol anticipated a high crossover rate and therefore did not include any comparative analyses after month 6.

18. Secondary Outcome

Title	Ambulatory Status
Description	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.
Time Frame	24 months (surgical group), 6 months (non-surgical group)

Outcome Measure Data

Analysis Population Description

Number of days to full ambulation among those without full ambulation at baseline. At baseline only 13 in the surgical arm were not Ambulatory without assistance and for the NSM group, it was only 5 at baseline.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months.. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	13	5
Median (95% Confidence Interval); Unit of Measure: Days, median
	60 [1]; (46 to NA)	NA [2]; (NA to NA)

[1]

Upper confidence limit not defined due to small sample size.

[2]

By month 6, only 40% of non-ambulatory NSM subjects regained full ambulation status

19. Secondary Outcome

Title	Work Status
Description	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.
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

Patients not working at baseline due to back or other pain. Note this is a subset of the entire population.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	26	12
Measure Type: Count of Participants; Unit of Measure: Participants
	2 7.7%	0 0.0%

20. Secondary Outcome

Title	Work Status
Description	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.
Time Frame	3 Months

Outcome Measure Data

Analysis Population Description

Patients not working at baseline due to back or other pain

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	26	12
Measure Type: Count of Participants; Unit of Measure: Participants
	3 11.5%	0 0.0%

21. Secondary Outcome

Title	Work Status
Description	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.
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

Patients not working at baseline due to back or other pain

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	26	12
Measure Type: Count of Participants; Unit of Measure: Participants
	5 19.2%	0 0.0%

22. Secondary Outcome

Title	Work Status
Description	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.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

Patients not working at baseline due to back or other pain

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	26	6
Measure Type: Count of Participants; Unit of Measure: Participants
	4 15.4%	NA [1]

[1]

The intended analysis was to examine differences in responses at 6 months. The protocol anticipated a high crossover rate and therefore did not include any comparative analyses after month 6.

23. Secondary Outcome

Title	Work Status
Description	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.
Time Frame	18 Months

Outcome Measure Data

Analysis Population Description

Patients not working at baseline due to back or other pain

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	23	5
Measure Type: Count of Participants; Unit of Measure: Participants
	3 13.0%	NA [1]

[1]

The intended analysis was to examine differences in responses at 6 months. The protocol anticipated a high crossover rate and therefore did not include any comparative analyses after month 6.

24. Secondary Outcome

Title	Work Status
Description	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.
Time Frame	24 Months

Outcome Measure Data

Analysis Population Description

Patients not working at baseline due to back or other pain

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM followed to 6 months. Subjects were allowed to cross over to other treatments (including surgical treatments) after the month 6 visit was complete.
Overall Number of Participants Analyzed	23	5
Measure Type: Count of Participants; Unit of Measure: Participants
	2 8.7%	NA [1]

[1]

The intended analysis was to examine differences in responses at 6 months. The protocol anticipated a high crossover rate and therefore did not include any comparative analyses after month 6.

25. Secondary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs)
Description	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.
Time Frame	Procedure, discharge, 1, 3, 6, 12, 18 and 24 months

Outcome Measure Data

Analysis Population Description

All treated study subjects.

Arm/Group Title	iFuse Implant System	Non-Surgical Management
Arm/Group Description:	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery	This arm includes all subjects randomized to NSM. Many of these subjects crossed over to treatment after 6 months of NSM.
Overall Number of Participants Analyzed	102	46
Measure Type: Count of Participants; Unit of Measure: Participants
	38 37.3%	12 26.1%

Adverse Events

Time Frame	1 month, 3 months, 6 months, 12 months, 18 months, 24 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	iFuse Implant System		Non-Surgical Management
Arm/Group Description	Surgical placement of iFuse implants in the affected SI joint iFuse Implant System: Placement of iFuse implant system via surgery		This arm includes all subjects randomized to NSM followed to 6 months Non-surgical management: Medications for pain, physical therapy, SI joint injection and RF ablation.
All-Cause Mortality
	iFuse Implant System		Non-Surgical Management
	Affected / at Risk (%)		Affected / at Risk (%)
Total	1/102 (0.98%)		1/46 (2.17%)
Serious Adverse Events
	iFuse Implant System		Non-Surgical Management
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/102 (37.25%)		12/46 (26.09%)
Cardiac disorders
Syncope †	2/102 (1.96%)	2	0/46 (0.00%)	0
Coronary artery disease †	1/102 (0.98%)	1	0/46 (0.00%)	0
Myocardial infarction - fatal † [1]	1/102 (0.98%)	1	0/46 (0.00%)	0
Eye disorders
Glaucoma †	0/102 (0.00%)	0	1/46 (2.17%)	1
Gastrointestinal disorders
Gastroenteritis †	1/102 (0.98%)	1	0/46 (0.00%)	0
Small bowel obstruction †	0/102 (0.00%)	0	1/46 (2.17%)	1
Gastroparesis †	1/102 (0.98%)	1	0/46 (0.00%)	0
Bowel obstruct, leading to surgery † [2]	1/102 (0.98%)	1	0/46 (0.00%)	0
Esophagitis †	1/102 (0.98%)	1	0/46 (0.00%)	0
Gastric ulcer †	1/102 (0.98%)	1	0/46 (0.00%)	0
General disorders
Benign prostatic hypertrophy †	1/102 (0.98%)	1	0/46 (0.00%)	0
Hepatobiliary disorders
Cholecystitis †	1/102 (0.98%)	1	0/46 (0.00%)	0
Biliary colic †	1/102 (0.98%)	1	0/46 (0.00%)	0
Injury, poisoning and procedural complications
Wound hematoma †	1/102 (0.98%)	1	0/46 (0.00%)	0
Revision - SIJ pain †	2/102 (1.96%)	2	0/46 (0.00%)	0
Revision - neuropathy †	1/102 (0.98%)	1	0/46 (0.00%)	0
Neuropathy - Resolved with revision †	0/102 (0.00%)	0	1/46 (2.17%)	1
Atrial fibrillation / respira failure †	1/102 (0.98%)	1	0/46 (0.00%)	0
Metabolism and nutrition disorders
Diabetes mellitus †	1/102 (0.98%)	1	0/46 (0.00%)	0
Musculoskeletal and connective tissue disorders
Osteoarthritis of the knee †	1/102 (0.98%)	1	0/46 (0.00%)	0
Meniscal tear †	4/102 (3.92%)	4	1/46 (2.17%)	2
Contralateral SIJ pain †	10/102 (9.80%)	10	0/46 (0.00%)	0
Degenerative disease - spine †	7/102 (6.86%)	7	1/46 (2.17%)	1
Ankle fracture †	0/102 (0.00%)	0	1/46 (2.17%)	1
Disc herniation †	1/102 (0.98%)	2	0/46 (0.00%)	0
Rotator cuff tear †	1/102 (0.98%)	1	0/46 (0.00%)	0
Back pain †	3/102 (2.94%)	3	1/46 (2.17%)	1
Ipsilateral - SIJ pain †	0/102 (0.00%)	0	1/46 (2.17%)	1
Osteoarthritis of the hip †	2/102 (1.96%)	2	0/46 (0.00%)	0
Avascular necrosis of left hip †	0/102 (0.00%)	0	1/46 (2.17%)	1
Hip revision †	1/102 (0.98%)	1	0/46 (0.00%)	0
Restrolisthesis T12-L1 †	1/102 (0.98%)	1	0/46 (0.00%)	0
Fracture - tibia / fibula †	0/102 (0.00%)	0	1/46 (2.17%)	1
Knee pain †	0/102 (0.00%)	0	1/46 (2.17%)	1
Labral tear & ilium fracture †	1/102 (0.98%)	1	0/46 (0.00%)	0
Snapping scapula syndrome †	0/102 (0.00%)	0	1/46 (2.17%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Dysfunctional uterine bleeding †	1/102 (0.98%)	1	0/46 (0.00%)	0
Nervous system disorders
S1 neuropathy †	1/102 (0.98%)	1	0/46 (0.00%)	0
Seizure †	0/102 (0.00%)	0	1/46 (2.17%)	1
Psychiatric disorders
Depression †	1/102 (0.98%)	1	0/46 (0.00%)	0
Renal and urinary disorders
Kidney disfunction due to nsaid †	0/102 (0.00%)	0	1/46 (2.17%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism †	1/102 (0.98%)	1	0/46 (0.00%)	0
COPD †	0/102 (0.00%)	0	1/46 (2.17%)	1
Pleurisy †	1/102 (0.98%)	1	0/46 (0.00%)	0
Pneumonia †	0/102 (0.00%)	0	1/46 (2.17%)	1
† Indicates events were collected by systematic assessment; [1] Myocardial infarction - fatal; [2] Bowel obstruct, leading to surgery
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	iFuse Implant System		Non-Surgical Management
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	69/102 (67.65%)		35/46 (76.09%)
Infections and infestations
Upper respiratory infection †	5/102 (4.90%)	5	4/46 (8.70%)	5
Musculoskeletal and connective tissue disorders
Knee pain †	6/102 (5.88%)	7	3/46 (6.52%)	3
Back pain †	27/102 (26.47%)	29	8/46 (17.39%)	8
Degenerative disease - spine †	17/102 (16.67%)	19	12/46 (26.09%)	16
SIJ pain - ipsilateral †	13/102 (12.75%)	14	10/46 (21.74%)	11
Shoulder pain †	8/102 (7.84%)	8	2/46 (4.35%)	2
SIJ pain - contralateral †	12/102 (11.76%)	12	6/46 (13.04%)	6
Trochanteric bursitis †	12/102 (11.76%)	14	4/46 (8.70%)	4
Leg pain †	0/102 (0.00%)	0	4/46 (8.70%)	5
Hip pain †	7/102 (6.86%)	7	0/46 (0.00%)	0
† Indicates events were collected by systematic assessment

Limitations and Caveats

Open-label (non-blinded) study. Most (>90%) NSM subjects with continued pain crossed over after the 6-month visit. Analysis across groups after 6 months is therefore biased, since surgery by definition is not a component of non-surgical treatment.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Daniel Cher, Vice President of Clinical Affairs
• Organization: SI-BONE, Inc.
• Phone: 408-207-0700
• EMail: dcher@si-bone.com

Publications of Results:

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.

• Responsible Party: SI-BONE, Inc.
• ClinicalTrials.gov Identifier: NCT01681004
• Other Study ID Numbers: 300103
• First Submitted: September 1, 2012
• First Posted: September 7, 2012
• Results First Submitted: June 22, 2017
• Results First Posted: August 25, 2017
• Last Update Posted: August 25, 2017