Clinical trial NCT04073563: Transforaminal Lumbar Interbody Fusion (TLIF)
Official title: Prospective, Randomized, Controlled, Blinded Pivotal Study In Subjects Undergoing A Transforaminal Lumbar Interbody Fusion (TLIF) At One Or Two Levels Using Infuse™ Bone Graft With an Intervertebral Body Fusion Device and Posterior Supplemental Fixation For The Treatment Of Symptomatic Degenerative Disease Of The Lumbosacral Spine
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Degenerative Disease of the Lumbosacral Spine
Lead sponsor: Medtronic Spinal and Biologics
Sponsor class: INDUSTRY
First posted: 2019-08-29
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a global, multi-center, prospective, randomized, blinded, controlled pivotal study. Clinical and radiological evaluation will be performed preoperatively and postoperatively up to 24 months; and endpoint success will be determined at 24 months postoperatively.

Overall a maximum of 600 subjects will be enrolled and treated. The purpose of the study is to provide safety and effectiveness data of Infuse™ in Transforaminal Lumbar Interbody Fusion (TLIF) procedures and to obtain indication expansion for Infuse™ use in one and two level TLIF procedures.


Eligibility criteria: Inclusion Criteria:

A subject must meet all of the following inclusion criteria to participate in this study:

* I.1. Has degenerative disease of the lumbosacral spine in one or two adjacent levels (L2 to S1) that results in radiculopathy secondary to nerve root compression, manifested by:

  1. History of radiating leg or buttock pain, paresthesia, numbness or weakness, or
  2. History of neurogenic claudication.
* I.2. Has a history of low back pain.
* I.3. Has radiographic evidence (e.g. CT, MRI, x-ray, etc.) of degenerative lumbosacral disease including at least one of the following:

  1. Instability up to and including Grade 2 spondylolisthesis/retrolisthesis based on the Meyerding classification (Meyerding, HW, 1932), or lateral listhesis demonstrated by coronal plane translation (slippage) of the superior (cranial) vertebral body lateral to the inferior (caudal) vertebral body less than or equal to 3mm, or
  2. Stenosis, or narrowing, of the lumbar spinal canal and/or intervertebral foramen requiring significant decompression leading to segmental instability, or
  3. Recurrent disc herniation
* I.4. Has preoperative Oswestry Disability Index score ≥ 35.

Has to meet either inclusion criteria 5 or 6 to qualify for the study:

* I.5. Has preoperative back and leg pain scores of (back pain ≥ 4 and leg pain ≥ 1) based on the Preoperative Back and Leg Pain Questionnaire.
* I.6. Has preoperative back and leg pain scores of (back pain ≥ 1 and leg pain ≥ 4) based on the Preoperative Back and Leg Pain Questionnaire.
* I.7. Is at least 18 years of age and skeletally mature at the time of surgery.
* I.8. Has not responded to non-operative treatment (e.g., bed rest, physical therapy, medications, spinal injections, manipulation, and/or TENS) for a period of six months.
* I.9. Is willing and able to comply with the study plan and able to understand and sign the subject Informed Consent Form.

Exclusion Criteria:

A subject will be excluded from participating in this study for any of the following reasons:

* E.1 Prior surgical procedure at the involved or adjacent spinal levels (e.g. fusion, arthroplasty, and/or other non-fusion procedures). Prior discectomy and/or laminectomy at the target or adjacent levels is allowed.
* E.2 Significant lumbar instability defined as sagittal listhesis greater than Grade 2 at any involved level using the Meyerding Classification or lateral listhesis greater than 3 mm at any involved level.
* E.3 Planned use of an internal or external bone growth stimulator.
* E.4 Lumbar scoliosis \>30 degrees.
* E.5 Patients who had a previous diagnosis of osteoporosis with a T-score of -2.5 or below in the last 12 months existing together with a prevalent fragility fracture. (If subject has a prevalent fragility fracture and a T-score hasn't been assessed in the last 12 months, a DEXA will need to be obtained.)
* E.6 Morbidly obese, as defined by a Body Mass Index (BMI) \>40.
* E.7 Presence of active malignancy or prior history of malignancy (non-invasive basal cell carcinoma of the skin and non-invasive squamous cell carcinoma localized only to the skin is allowed).
* E.8 Overt or active bacterial infection, either local to surgical space or systemic.
* E.9 Has undergone administration of any type of corticosteroid, antineoplastic, immunostimulating, or immunosuppressive agents, or medications known to inhibit the healing of bone or soft tissue within 30 days prior to implantation of the assigned treatment.

  * This includes patients ≥ 65 years of age taking warfarin with documented diagnosed osteoporosis. All other patients taking warfarin should washout for at least 5 days prior to treatment
  * Use of steroidal inhalers is allowed pre- and post-operatively
  * Short-term steroidal use (e.g., Medrol Dosepak) is allowed pre and post-operatively. For this clinical study, short-term use is defined as ≤ two weeks. Use of steroids for longer than two weeks post-operatively through the 24-month follow-up visit is prohibited.
* E.10 Co-morbidities, which in the investigator's opinion, precludes the subject from being a surgical candidate.
* E.11 Autoimmune disease, which in the investigator's opinion, is known to affect bone metabolism or the spine (e.g., spondyloarthropathies, juvenile arthritis, rheumatoid arthritis, Graves' disease, Hashimoto's thyroiditis).
* E.12 Any endocrine or metabolic disorder, which in the investigator's opinion, is known to affect osteogenesis (e.g., Paget's disease, renal osteodystrophy, Ehlers-Danlos syndrome, or osteogenesis imperfecta).
* E.13 Known exposure to any recombinant proteins used for bone formation (e.g., 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).
* E.14 Known 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; and/or instrumentation materials (e.g., titanium, titanium alloy, cobalt chrome, cobalt chrome alloy, or PEEK).
* E.15 History of any allergy resulting in anaphylaxis.
* E.16 Is a prisoner.
* E.17 Is mentally incompetent. If questionable, obtain psychiatric consult.
* E.18 Treatment with an investigational therapy (drug, device, and/or biologic) targeting spinal conditions within 3 months prior to implantation surgery, treatment with any other investigational therapies within 30 days prior to implantation surgery, or such treatment is planned during the 24-month period following implantation of the study treatment.
* E.19 Pregnant or nursing. Females of child-bearing potential must agree not to become pregnant for 24 months following surgery.
* E.20 A documented diagnosis of substance use disorder as defined by the DSM-5.22 (Nicotine use is allowed.)
* E.21 Pursuing worker's compensation or active litigation for spinal fusion procedure.
* E.22 Any condition, which in the investigator's opinion, would interfere with the subject's ability to comply with study instructions, which might confound data interpretation.

Primary outcomes:
measure: Overall success at 24 months
timeFrame: 24 months
measure: Fusion success at 24 months
timeFrame: 24 Months
Secondary outcomes:
measure: Time to fusion
timeFrame: From surgery to 24 Months
measure: ODI success
timeFrame: 24 months
measure: Leg pain success
timeFrame: 24 months
measure: Back pain success
timeFrame: 24 months
measure: Neurological success
timeFrame: 24 months
measure: Serious Adverse Events
timeFrame: up to 24 months
measure: Secondary Surgery
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Brain and Spine, HonorHealth
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Laguna Hills
country: United States
facility: Memorial Health Services
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Spine Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Boulder
country: United States
facility: Boulder Neurosurgical Associates and Justin Parker Neurological Institute/E. Lee Nelson
state: Colorado
city: Vail
country: United States
facility: Vail-Summit Orthopaedics and Neurosurgery
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Altamonte Springs
country: United States
facility: Advent Health Altamonte Springs
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Orlando
country: United States
facility: Advent Health Orlando
state: Florida
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Tampa
country: United States
facility: Foundation for Orthopaedic Research and Education
state: Florida
city: Chicago
country: United States
facility: Northwestern Medicine
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Carmel
country: United States
facility: Goodman Campbell Brain and Spine
state: Indiana
city: Carmel
country: United States
facility: Indiana Spine Group
state: Indiana
city: Indianapolis
country: United States
facility: OrthoIndy Northwest Office
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinic
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute
state: Kansas
city: Burlington
country: United States
facility: Lahey Hospital & Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: Mayfield Brain and Spine Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Hershey
country: United States
facility: Penn State-Hershey
state: Pennsylvania
city: Philadelphia
country: United States
facility: Rothman Institute
state: Pennsylvania
city: Memphis
country: United States
facility: Semmes Murphey
state: Tennessee
city: Nashville
country: United States
facility: Saint Thomas for Specialty Surgery
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Orthopaedic Alliance
state: Tennessee
city: Austin
country: United States
facility: Ascension Texas Spine and Scoliosis
state: Texas
city: Fort Worth
country: United States
facility: DFW Center for Spinal Disorder
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Plano
country: United States
facility: American Neurospine Institute
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia - Clinical Trial Office
state: Virginia
city: Charlottesville
country: United States
facility: University of Virginia - Health System
state: Virginia
city: Seattle
country: United States
facility: Swedish Neuroscience
state: Washington
city: Morgantown
country: United States
facility: West Virginia University, 1 Medical Center Drive
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Beijing
country: China
facility: Peking University Third Hospital
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
city: Chongqing
country: China
facility: Chongqing Xinqiao Hospital Second Affiliated Hospital of Army Medical University
Study officials:
References: