A Study of Infuse® Bone Graft With Mastergraft® Strip and Posterior Fixation for Posterolateral Fusion (PLF) Treatment of Multi-Level Degenerative Lumbosacral Spinal Conditions

• ClinicalTrials.gov Identifier: NCT03118505
• Recruitment Status: Recruiting
• First Posted: April 18, 2017
• Last Update Posted: December 4, 2020
• Sponsor: Medtronic Spinal and Biologics
• Information provided by (Responsible Party): Medtronic Spinal and Biologics

Study Description

Brief Summary:

The purpose of this study is to obtain safety and effectiveness data on the investigational device for multi-level PLF procedures and determine the most appropriate rhBMP-2 dose for use in this indication. The study information may be used for a potential pivotal study design.

Condition or disease	Intervention/treatment	Phase
Multi-Level Degenerative Lumbosacral Spinal Conditions	Device: Infuse Bone Graft; Device: Medtronic DBM	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 125 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized, Multi-Center, Open-Label Pilot Study of Infuse® Bone Graft With Mastergraft® Strip and Posterior Fixation for Posterolateral Fusion (PLF) Treatment of Multi-Level Degenerative Lumbosacral Spinal Conditions
• Actual Study Start Date: June 29, 2017
• Estimated Primary Completion Date: October 2023
• Estimated Study Completion Date: October 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1; Infuse Bone Graft [4.2 mg per operative level] + Mastergraft Strip + local bone autograft + posterior fixation	Device: Infuse Bone Graft; Infuse Bone Graft + Mastergraft Strip + local bone autograft + posterior fixation
Experimental: Group 2; Infuse Bone Graft [6 mg per operative level] + Mastergraft Strip + local bone autograft + posterior fixation	Device: Infuse Bone Graft; Infuse Bone Graft + Mastergraft Strip + local bone autograft + posterior fixation
Experimental: Group 3; Infuse Bone Graft [12 mg per operative level] + Mastergraft Strip + local bone autograft + posterior fixation	Device: Infuse Bone Graft; Infuse Bone Graft + Mastergraft Strip + local bone autograft + posterior fixation
Active Comparator: Control; Medtronic DBM + local bone autograft (and supplemented with iliac crest bone graft (ICBG), if needed) + posterior fixation.	Device: Medtronic DBM; Medtronic DBM + local bone autograft (and supplemented with iliac crest bone graft (ICBG), if needed) + posterior fixation

Outcome Measures

Primary Outcome Measures :

1. Radiological Fusion Success [ Time Frame: 12 months ]

   Fusion at each treated level is defined as radiological fusion assessed by radiograph and CT. A subject will be considered a fusion success when the following criteria are met for each treated level:

   • Bilateral bridging bone (superior transverse process to the inferior transverse process) at each treated level (CT);
   • No more than 3mm translational motion and less than 5 degrees in angular motion at each treated level (flexion/extension radiographs); and
   • Absence of cracking, as evidenced by radiolucent lines completely through the fusion mass (all radiograph views).

Secondary Outcome Measures :

1. Overall success rate at 12 and 24 months [ Time Frame: 12 and 24 months ]

   Overall success is defined as the participant who meet the following five criteria:

   • Radiographic success, defined as radiological fusion success in the posterolateral space;
   • Pain/disability (ODI) success, defined as at least a 15-point improvement from baseline;
   • Neurological success, defined as maintenance or improvement in neurological status;
   • No SAE related to the PLF grafting material or posterior fixation; and
   • No secondary surgeries classified as a "failure."
2. ODI score at 12 and 24 months [ Time Frame: 12 and 24 months ]
   The self-administered Oswestry Disability Index (ODI) Questionnaire (Version 2.1) will be used to assess patient pain and ability to function. The ODI scale ranges from 0-100. The best score is 0 (no disability) and worst is 100 (maximum disability).
3. ODI success rate at 12 and 24 months [ Time Frame: 12 and 24 months ]
   ODI success is defined as at least a 15-point improvement from baseline.
4. Neurological success rate at 12 and 24 months [ Time Frame: 12 and 24 months ]
   Overall neurological success is defined as maintenance or improvement in four key neurological assessments: motor function, sensory function, reflexes, and straight leg raise. In order to be considered a success, each element in the motor, sensory, reflexes, and straight leg raise examinations must remain the same or improve from the time of the preoperative evaluation to the time period evaluated.
5. Back pain score at 12 and 24 months [ Time Frame: 12 and 24 months ]
   Numerical rating scales, adapted in part from Measuring Health, will be used to evaluate back pain. The back pain score (0-20) is the summation of pain intensity (0-10) and duration (0-10) scores.
6. Back pain success at 12 and 24 months [ Time Frame: 12 and 24 months ]
   Back pain success is defined as at least 30% improvement from baseline.
7. Leg pain score at 12 and 24 months [ Time Frame: 12 and 24 months ]
   Numerical rating scales, adapted in part from Measuring Health, will be used to evaluate leg pain. The leg pain score (0-20) is the summation of pain intensity (0-10) and duration (0-10) scores.
8. Leg pain success at 12 and 24 months [ Time Frame: 12 and 24 months ]
   Leg pain success is defined as at least 30% improvement from baseline.
9. Radiological fusion success rate at 24 months [ Time Frame: 24 months ]

   Fusion at each treated level is defined as radiological fusion assessed by radiograph and CT. A subject will be considered a fusion success when the following criteria are met for each treated level:

   • Bilateral bridging bone (superior transverse process to the inferior transverse process) at each treated level (CT);
   • No more than 3mm translational motion and less than 5 degrees in angular motion at each treated level (flexion/extension radiographs); and
   • Absence of cracking, as evidenced by radiolucent lines completely through the fusion mass (all radiograph views).
10. AEs related to the PLF grafting material or posterior fixation up to 24 months [ Time Frame: 24 months ]
    A summary of AEs related to the PLF grafting material or posterior fixation up to 24 months.
11. Secondary surgeries related to the PLF grafting material or posterior fixation up to 24 months [ Time Frame: 24 months ]
    A summary of secondary surgeries related to the PLF grafting material or posterior fixation up to 24 months

Eligibility Criteria

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Degenerative lumbar spine condition:

   1. Requiring a PLF procedure using a bilateral metallic screw and rod system in 2-4 consecutive levels from L2-S1; and
   2. Diagnosed with: instability (up to and including Grade 2 spondylolisthesis, retrolisthesis, or lateral listhesis), stenosis with documented pre-operative instability, and/or recurrent disc herniation, any of which may have possible concomitant lumbar degenerative deformity (Cobb angle ≤ 30 degrees).
2. Preoperative ODI score ≥40.
3. Preoperative pain score of ≥8 (out of 20) on the Preoperative Leg Pain Questionnaire.
4. Most inferior treated spinal level is able to accommodate an interbody fusion device.
5. ≥21 years of age at the time of signing the informed consent.
6. Failed ≥6 months non-operative treatment (e.g., bed rest, physical therapy, medications, spinal injections, manipulation, and/or TENS).
7. Is willing and able to comply with the study plan and able to understand and sign the Subject Informed Consent Form.

Exclusion Criteria:

1. Prior spinal fusion surgical procedure at the involved or adjacent spinal levels. (Prior non-fusion surgery at the target levels, including discectomy and/or single-level foraminotomy or laminectomy, is allowed.)
2. Prior lumbar disc arthroplasty.
3. Significant lumbar instability, defined as sagittal listhesis >Grade 2 at any involved level using Meyerding's Classification or lateral listhesis >25% lateral translation at any involved level.
4. Planned use of an internal or external bone growth stimulator.
5. Lumbar scoliosis >30 degrees.
6. Osteoporosis to a degree that spinal instrumentation is contraindicated or a history of atraumatic vertebral fracture.
7. Morbidly obese, as defined by a Body Mass Index (BMI) >40.
8. Presence of active malignancy or prior history of malignancy.
9. Overt or active bacterial infection, either local or systemic.
10. Has undergone systemic administration of any type of corticosteroid, anti-neoplastic, immunostimulating, or immunosuppressive agents within 30 days prior to implantation of the assigned treatment.
11. Comorbidities precluding subject from being a surgical candidate.
12. History of autoimmune disease known to affect bone metabolism or the spine (e.g., spondyloarthropathies, juvenile arthritis, rheumatoid arthritis, Graves' disease, Hashimoto's thyroiditis).
13. History of any endocrine or metabolic disorder known to affect osteogenesis (e.g., Paget's disease, renal osteodystrophy, Ehlers-Danlos syndrome, or osteogenesis imperfecta).
14. History of exposure to any recombinant proteins used for bone formation (i.e., Infuse Bone Graft, OP-1 Putty, OP-1 Implant, AUGMENT Bone Graft, GEM21S, i-FACTOR Peptide Enhanced Bone Graft, or PepGen P-15 Synthetic Bone Graft).
15. Hypersensitivity or allergy to any components of the study treatments including, but not limited to, bone morphogenetic proteins (BMPs); injectable collagen; protein pharmaceuticals (e.g., monoclonal antibodies or gamma globulins); bovine collagen products; gentamicin or glycerol (which may be present in trace amounts in the DBM products); and/or instrumentation materials (titanium, titanium alloy, cobalt chrome, cobalt chrome alloy, or polyetheretherketone [PEEK]).
16. History of any allergy resulting in anaphylaxis.
17. Is a prisoner.
18. Is mentally incompetent. If questionable, obtain psychiatric consult.
19. Treatment with an investigational therapy (drug, device, and/or biologic) within 30 days prior to implantation surgery, or such treatment is planned during the 24-month period following implantation of the study treatment.
20. Pregnant or nursing. Females of child-bearing potential must agree not to become pregnant for one year following surgery.
21. Any condition that would interfere with the subject's ability to comply with study instructions, might confound the interpretation of the study, or put the subject at risk.

Contacts and Locations

Locations

United States, California

University of California, Davis; Recruiting

Sacramento, California, United States, 95816

Contact: Nancy Rudisill 916-551-3234 narudisill@ucdavis.edu

Principal Investigator: Kee Kim, MD

Sub-Investigator: Julius Ebinu, MD

Sub-Investigator: Ronaldo Roberto, MD

United States, Colorado

Spine Colorado; Active, not recruiting

Durango, Colorado, United States, 81301

The Steadman Clinic; Active, not recruiting

Vail, Colorado, United States, 81657

United States, Florida

The Spine Health Institute; Recruiting

Altamonte Springs, Florida, United States, 32701

Contact: Pamela Carrigan 407-303-2367 Pamela.Carrigan@flhosp.org

Principal Investigator: Chetan Patel, MD

Foundation for Orthopedic Research and Education; Recruiting

Tampa, Florida, United States, 33637

Contact: Deborah Warren, RN, CCRC 813-978-9700 ext 6766 dwarren@foreonline.org

Principal Investigator: John Small, MD

United States, Georgia

Emory University; Active, not recruiting

Atlanta, Georgia, United States, 30329

United States, Indiana

Indiana Spine Group; Recruiting

Carmel, Indiana, United States, 46032

Contact: Sheetal Vinayek, M.Sc 317-715-5897 svinayek@indianaspinegroup.com

Principal Investigator: Joseph Smucker, MD

Sub-Investigator: Paul Kraemer, MD

Fort Wayne Orthopedics; Terminated

Fort Wayne, Indiana, United States, 46804

United States, Kansas

The University of Kansas (KUMC); Terminated

Kansas City, Kansas, United States, 66160

United States, Michigan

Bronson Methodist Hospital; Active, not recruiting

Kalamazoo, Michigan, United States, 49007

United States, New York

Upstate Orthopedics; Recruiting

East Syracuse, New York, United States, 13057

Contact: Tina Craig 315-464-8618 craigt@upstate.edu

Principal Investigator: William Lavelle, MD

Sub-Investigator: Richard Tallarico, MD

United States, Texas

Seton Spine & Scoliosis Center; Active, not recruiting

Austin, Texas, United States, 78731

United States, Virginia

University of Virginia; Recruiting

Charlottesville, Virginia, United States, 22903

Contact: Lorrie Sipe 434-924-8775 LAG3K@hscmail.mcc.virginia.edu

Principal Investigator: Mark E. Shaffrey, MD

Sub-Investigator: Chun-Po Yen, MD

Sub-Investigator: Avery L. Buchholz, MD

Sponsors and Collaborators

Medtronic Spinal and Biologics

More Information

• Responsible Party: Medtronic Spinal and Biologics
• ClinicalTrials.gov Identifier: NCT03118505
• Other Study ID Numbers: P16-03
• First Posted: April 18, 2017
• Last Update Posted: December 4, 2020
• Last Verified: December 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Additional relevant MeSH terms:

Disease; Pathologic Processes