Accell Evo3™ Demineralized Bone Matrix in Instrumented Lumbar Spine Fusion

• Sponsor: SeaSpine, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02018445
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arm: 1
• Duration (Months): 42
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The objective of this study is to prospectively evaluate the performance of Integra Accell Evo3 Demineralized Bone Matrix as an adjunct for instrumented posterolateral spine fusion, as compared to local autograft.

Condition or Disease	Intervention/Treatment	Phase
Degenerative Changes; Stenosis; Spondylosis	Procedure: Posterolateral Fusion	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Other: Accell Evo3 DBM & Local Autograft Accell Evo3 DBM (posterolateral gutter symptomatic side) and Local Autograft (posterolateral gutter contralateral non-symptomatic side)	Procedure: Posterolateral Fusion

Outcome Measures

Primary Outcome Measures

1. Time to Arthrodesis (Fusion) for Each Spinal Level (Unit), as Measured by X-rays. [12 months]

   There were 29 patients and 43 total spinal levels (unit) treated at baseline. Time to arthodesis was measured as the mean time to achieve fusion. At each time point fusion was evaluated, the first time point fusion was achieved was considered fusion.

Secondary Outcome Measures

1. Percent (%) of Fusion for Each Spinal Level (Unit), as Measured by Computed Tomography (CT) Scan [12 months]

2. Medical Outcomes: Oswestry Disability Index (ODI) [12 months]

   The ODI is an index derived from the Oswestry Low Back Pain Questionnaire used by surgeons, clinicians and researchers to quantify disability for low back pain. The questionnaire is self-completed and covers 10 topics about pain intensity, lifting, ability to care for oneself, ability to walk, ability to sit, sexual function, ability to stand, social life, sleep quality, and ability to travel. Scores are from 0-100 and a lower score represents a better score.

3. Medical Outcomes: Worst Leg Pain Visual Analog Scale (VAS) [12 months]

   The visual analogue scale (VAS) is a commonly used outcome measure for research studies. It is presented as a 100-mm horizontal line on which the patient's pain intensity is represented by a point between the extremes of "0"/no pain at all" and "100/worst pain imaginable." The study in this scale is used for the worst leg pain. A lower score represents a better score.

4. Medical Outcomes: Back Pain Visual Analog Scale (VAS) [12 months]

   The visual analogue scale (VAS) is a commonly used outcome measure for research studies. It is presented as a 100- mm horizontal line on which the patient's pain intensity is represented by a point between the extremes of "0"/no pain at all" and "100/worst pain imaginable." The study in this scale is used for the back pain. A lower score represents a better score.

5. Medical Outcomes: Measure of EQ-5D™ Visual Analog Scale (VAS). [12 months]

   EQ-5D is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments. The EQ-5D consists of a descriptive system and the EQ VAS. The EQ-5D-5l has a descriptive system and the EQ visual analogue scale (EQ VAS). The EQ VAS records the patient's self-rated health on a vertical visual analogue scale. Only the EQ VAS Score was analyzed in the study. The EQ VAS scored from 0-100 and a lower score represents a better score.

6. Medical Outcomes: Maintenance of Lower Extremity Neurological Function [12 months]

   Posterolateral fusion study in which one spinal level is treated with both the study and control arm. One posterolateral spinal side is Evo3 and the other posterolateral spinal side is local autograft. NA (Not Applicable): Neurological function data was not able to be analyzed as there was a limitation of the method in the ability to distinguish between left and right side neurological function. Neurological function is indistinguishable between the right and left side of the lower extremities using the methods in the protocol and analysis of neurological function therefore would have made no impact on the outcome of the study.

7. Number of Patients With Serious Adverse Events, Adverse Device Effects, Serious Adverse Device Effects and Subsequent Surgical Interventions [24 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Are 18 (eighteen) years of age or older at the time of surgery.

2. Require spinal fusion using Transforaminal Lumbar Interbody Fusion (TLIF), Posterior Lumbar Fusion (PLF) or Posterior Lumbar Interbody Fusion (PLIF), with or without the use of an interbody spacer, at 1 to 3 levels between L3-S1.

3. Willing and able to return for the scheduled follow-up visits, follow post-operative instructions and undergo the required radiographic exams (A/P, Lateral Neutral and Lateral Flexion/Extension X-rays) for up to 4 time points between 2 weeks and 12 months post-surgery (3 months ± 2 weeks, 6±1 months, 12±2 months and if required 24±3 months post-surgery), including one CT-scan at 12±2 months.

4. Unresponsive to conservative care over a period of at least 6 months or has signs and/or symptoms that mandate urgent surgical intervention.

5. Willing and able to sign study specific informed consent.

Exclusion Criteria:

1. Are long term users of medications (i.e. steroids greater than 8 days) that are known to inhibit fusion or bone metabolism at any time within 6 months prior to surgery. Exceptions are inhaled steroids for asthma treatment (i.e. subjects on inhaled steroids are allowed), or epidural steroid injections.

2. Are taking immunosuppressive agents (Cancer chemotherapy, treatment with Disease Modifying Anti-rheumatic drugs (DMARDs) or any similar immunomodulating drugs) or are treated with Growth Factors or Insulin at any time within 6 months prior to surgery.

3. Are being treated with radiotherapy.

4. Are having medical conditions, known to impact bone metabolism, such as Paget's disease, osteoporosis, severe degenerative bone disease.

5. Are smokers and/or nicotine/tobacco users.

6. Have a Body Mass Index (BMI) ≥ 40

7. Are pregnant, lactating or women wishing to become pregnant.

8. Are a prisoner.

9. Are currently participating in an investigational drug or device study that has not completed the primary endpoint or that clinically interferes with the study endpoints.

10. Prior spine surgery at the index level except posterior decompressive surgery where the posterior elements are preserved e.g. facet saving techniques such as discectomy, laminotomy, and intradiscal procedures.

11. Use of any other bone graft or bone graft substitute in addition to or in place of Accell Evo3 and/or local autograft.

12. Use of routine prophylactic NSAIDS for 3 months post-operatively, but low dose concomitant pain medications e.g. aspirin should be continued and recorded on the Concomitant Pain Medications case report form (CRF).

13. Have a known sensitivity Polymyxin Sulfate B, Bacitracin, Gentamycin and/or Iodine.

14. Severe vascular or neurological disease.

15. Uncontrolled diabetes.

16. Uncooperative patients who will not or cannot follow postoperative instructions, including individuals who abuse drugs and/or alcohol.

17. Renal impairment.

18. Active or latent infection in or around the surgical site.

19. Accell Evo3 is contraindicated when there is significant vascular impairment proximal to the implantation site and when there are metabolic or systemic bone disorders that affect bone or wound healing, or when stabilization of the defect is not possible.

20. The use of Accell Evo3 is also contraindicated in cases where intraoperative soft tissue coverage is not planned or possible and in infected or contaminated wounds.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Orthopaedic Surgical Group	Long Beach	California	United States	90806

Sponsors and Collaborators

• SeaSpine, Inc.

Investigators

• Principal Investigator: Philip Yuan, M.D, Memorial Orthopaedic Surgical Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: SeaSpine, Inc.
• ClinicalTrials.gov Identifier: NCT02018445
• Other Study ID Numbers: ACC3-US-2012-2
• First Posted: Dec 23, 2013
• Last Update Posted: Feb 18, 2020
• Last Verified: Feb 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Spondylosis

Study Results

Participant Flow

Recruitment Details	During the study in which each patient undergoes posterolateral fusion (PLF). During PLF, each spinal level is treated with two graft materials, the symptomatic posterolateral gutter is treated with study arm (Accel Evo3) and the contralateral non-symptomtic posterolateral gutter is treated with the control arm (local autograft).

Arm/Group Title	All Patients
Arm/Group Description	Posterolateral fusion study in which each patient undergoes posterolateral fusion (PLF). During the PLF, each spinal level is treated with two graft materials, the symptomatic posterolateral gutter is treated with study arm (Evo3) and the contralateral posterolateral gutter is treated with the control arm (local autograft).
Period Title: Overall Study
STARTED	36
COMPLETED	29
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	All Patients
Arm/Group Description
Overall Participants	29
Overall Spinal Levels	43
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.4 (11.3)
Sex: Female, Male (Count of Participants)
Female	20 69%
Male	9 31%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	28.39 (5.38)

Outcome Measures

1. Primary Outcome

Title	Time to Arthrodesis (Fusion) for Each Spinal Level (Unit), as Measured by X-rays.
Description	There were 29 patients and 43 total spinal levels (unit) treated at baseline. Time to arthodesis was measured as the mean time to achieve fusion. At each time point fusion was evaluated, the first time point fusion was achieved was considered fusion.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Time to arthodesis was measured as the mean time to achieve fusion for each spinal level treated.

Arm/Group Title	All Patients
Arm/Group Description	Posterolateral fusion: each spinal level is treated with two graft materials, the posterolateral gutter is treated with study arm (Accel Evo3) and the contralateral posterolateral gutter is treated with the control arm (local autograft).
Measure Participants	29
Measure Spinal Levels	43
Mean (Standard Deviation) [months to fusion]	6 (5.7)

2. Secondary Outcome

Title	Percent (%) of Fusion for Each Spinal Level (Unit), as Measured by Computed Tomography (CT) Scan
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group Description	Posterolateral fusion: each spinal level is treated with two graft materials, the posterolateral gutter is treated with study arm (Accel Evo3) and the contralateral posterolateral gutter is treated with the control arm (local autograft).
Measure Participants	34
Measure Posterolateral Sides	34
Count of Units [Posterolateral Sides]	26

3. Secondary Outcome

Title	Medical Outcomes: Oswestry Disability Index (ODI)
Description	The ODI is an index derived from the Oswestry Low Back Pain Questionnaire used by surgeons, clinicians and researchers to quantify disability for low back pain. The questionnaire is self-completed and covers 10 topics about pain intensity, lifting, ability to care for oneself, ability to walk, ability to sit, sexual function, ability to stand, social life, sleep quality, and ability to travel. Scores are from 0-100 and a lower score represents a better score.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Patients were lost to follow-up as study progressed

Arm/Group Title	All Patients
Arm/Group Description	Patients were treated at multiple levels. Accell Evo3 was placed in the posterolateral gutter of the symptomatic side and local autograft was used in the posterolateral gutter of the contralateral asymptomatic side.
Measure Participants	29
Baseline	47.6 (17.7)
6 Month	26.0 (16.9)
12 Month	25.0 (21.0)

4. Secondary Outcome

Title	Medical Outcomes: Worst Leg Pain Visual Analog Scale (VAS)
Description	The visual analogue scale (VAS) is a commonly used outcome measure for research studies. It is presented as a 100-mm horizontal line on which the patient's pain intensity is represented by a point between the extremes of "0"/no pain at all" and "100/worst pain imaginable." The study in this scale is used for the worst leg pain. A lower score represents a better score.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Patients lost to follow-up over course of the study.

Arm/Group Title	All Patients
Arm/Group Description	Patients were treated at multiple levels. Accell Evo3 was placed in the posterolateral gutter of the symptomatic side and local autograft was used in the posterolateral gutter of the contralateral asymptomatic side.
Measure Participants	29
Baseline	64.8 (28.8)
6 Month	15.3 (25.7)
12 Month	13.3 (25.2)

5. Secondary Outcome

Title	Medical Outcomes: Back Pain Visual Analog Scale (VAS)
Description	The visual analogue scale (VAS) is a commonly used outcome measure for research studies. It is presented as a 100- mm horizontal line on which the patient's pain intensity is represented by a point between the extremes of "0"/no pain at all" and "100/worst pain imaginable." The study in this scale is used for the back pain. A lower score represents a better score.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Patients were lost to follow-up as study progressed

Arm/Group Title	All Patients
Arm/Group Description	Patients were treated at multiple levels. Accell Evo3 was placed in the posterolateral gutter of the symptomatic side and local autograft was used in the posterolateral gutter of the contralateral asymptomatic side.
Measure Participants	29
Baseline Over Time: Baseline	66.1 (30.6)
6 Month	23.6 (28.4)
12 Month	22.3 (30.2)

6. Secondary Outcome

Title	Medical Outcomes: Measure of EQ-5D™ Visual Analog Scale (VAS).
Description	EQ-5D is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments. The EQ-5D consists of a descriptive system and the EQ VAS. The EQ-5D-5l has a descriptive system and the EQ visual analogue scale (EQ VAS). The EQ VAS records the patient's self-rated health on a vertical visual analogue scale. Only the EQ VAS Score was analyzed in the study. The EQ VAS scored from 0-100 and a lower score represents a better score.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Patients were loss to follow-up as clinical study progressed.

Arm/Group Title	All Patients
Arm/Group Description	Patients were treated at multiple levels. Accell Evo3 was placed in the posterolateral gutter of the symptomatic side and local autograft was used in the posterolateral gutter of the contralateral asymptomatic side.
Measure Participants	29
Baseline	73.0 (21.0)
6 Month	82.2 (13.5)
12 Month	81.8 (20.0)

7. Secondary Outcome

Title	Medical Outcomes: Maintenance of Lower Extremity Neurological Function
Description	Posterolateral fusion study in which one spinal level is treated with both the study and control arm. One posterolateral spinal side is Evo3 and the other posterolateral spinal side is local autograft. NA (Not Applicable): Neurological function data was not able to be analyzed as there was a limitation of the method in the ability to distinguish between left and right side neurological function. Neurological function is indistinguishable between the right and left side of the lower extremities using the methods in the protocol and analysis of neurological function therefore would have made no impact on the outcome of the study.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

NA (Not Applicable): Neurological function data was not able to be analyzed as there was a limitation of the method in the ability to distinguish between left and right side neurological function. Neurological function is indistinguishable between the right and left side of the lower extremities using the methods in the protocol.

Arm/Group Title	All Patients
Arm/Group Description	All patients
Measure Participants	0

8. Secondary Outcome

Title	Number of Patients With Serious Adverse Events, Adverse Device Effects, Serious Adverse Device Effects and Subsequent Surgical Interventions
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group Description
Measure Participants	36
Count of Participants [Participants]	8 27.6%

Adverse Events

Time Frame	24 months
Arm/Group Title	All Patients
Arm/Group Description	Patients were treated at multiple levels. Accell Evo3 was placed in the posterolateral gutter of the symptomatic side and local autograft was used in the posterolateral gutter of the contralateral asymptomatic side.
All Cause Mortality
	All Patients
	Affected / at Risk (%)	# Events
Total	0/36 (0%)
Serious Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	8/36 (22.2%)
Infections and infestations
Infection	2/36 (5.6%)	2
Musculoskeletal and connective tissue disorders
Fall resulting in injury	1/36 (2.8%)	2
Nervous system disorders
Pain	4/36 (11.1%)	5
Social circumstances
Alcohol Abuse	1/36 (2.8%)	1
Surgical and medical procedures
Device (non-study) complication	1/36 (2.8%)	1
wound drainage	1/36 (2.8%)	1
Other (Not Including Serious) Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	17/36 (47.2%)
Cardiac disorders
Elevated blood pressure	1/36 (2.8%)	1
Gastrointestinal disorders
Impacted bowel	1/36 (2.8%)	1
Immune system disorders
Medication reaction	2/36 (5.6%)	2
Musculoskeletal and connective tissue disorders
Minor fracture	2/36 (5.6%)	3
Muscle tear	1/36 (2.8%)	1
Fall on side with no reported outcome	1/36 (2.8%)	1
Nervous system disorders
Pain, stiffness, strain, or discomfort	11/36 (30.6%)	13
Skin and subcutaneous tissue disorders
Minor cut	2/36 (5.6%)	4
Rash	1/36 (2.8%)	1
Left ear carcinoma removed	1/36 (2.8%)	1
Surgical and medical procedures
Device (non-study) Complication	1/36 (2.8%)	1
Radiographic Haloing of Screws (non-study)	1/36 (2.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.