Clinical trial NCT02178605: rhBMP-2 in Cervical Arthrodesis
Official title: A Prospective Non-Randomized Investigation Of The Use Of Infuse® (rhBMP-2) In Cervical Arthrodesis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cervical Arthrodesis
Keywords: rhBMP-2
arthrodesis
cervical
Lead sponsor: Virginia Spine Institute
Sponsor class: OTHER
First posted: 2014-07-01
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients presenting at a single site and candidates for cervical arthrodesis

Brief summary: This prospective study will investigate the use of recombinant human bone morphogenetic protein (rhBMP-2) in the current surgical standard of care for cervical spine pathology. Specifically, the outcomes of three forms of cervical fusion will be investigated:

1. Anterior cervical fusion with rhBMP-2, allograft corticocancellous bone as an interbody device, and anterior cervical plate fixation.
2. Posterior cervical fusion with rhBMP-2, local bone graft, with or without posterior screw fixation.
3. A combination of the previous two approaches: a combined anterior-posterior cervical fusion with rhBMP-2.

Detailed description: SURGICAL TECHNIQUES

1. Anterior cervical fusion The technique of anterior cervical discectomy and arthrodesis of the spine has been previously described by Smith-Robinson (ref) and is an accepted technique for anterior cervical fusion. Upon completion of adequate decompression, a gentle distraction maneuver may be performed by using either Caspar distraction pins or an interbody spreading device, taking care to avoid injury to the endplates.

   The endplates are then prepared with the use of a rasp or high speed burr taken to both superior and inferior endplates to remove the cartilagenous material and identify the bony endplate. Once hemostasis is obtained, the appropriate size allograft implant is chosen. That implant is then defrosted and brought into the surgical field. Concurrently, rhBMP-2 ((INFUSE®) Medtronic, Inc. Minneapolis, MN) has been reconstituted with sterile water, placed on an absorbable (type I bovine) collage sponge (ACS), cut to deliver the appropriate dose to each spinal level and is on the field as well. The partial BMP/ACS sponge is inserted into each disc space level, posterior to the structural implant. The dosage of rhBMP-2 used is approximately 0.525 mg per disc level or interbody space treated.

   The interbody device utilized is LifeNet Health's VertiGraft® VG2®. In the case of these allograft intervertebral implants, product safety and efficacy has been validated and patented by LifeNet Health using both an Allowash® and Allowash XG® technology. This is an intensive decontamination, disinfection and scrubbing regimen to remove and inactivate both viruses and bacteria which may be present from the donor harvesting process. The Allowash® process removes virtually all cellular elements of the bone thereby providing an additional line of defense against infectious disease. The second step consists of terminal sterilization of the cortico-cancellous allograft tissue. These processes have been validated and render the tissue sterile without compromising either the biomechanical or biochemical properties of allograft tissue intended for spinal applications.

   Plate fixation with the Atlantis® Cervical Plate (Medtronic, Inc. Minneapolis, MN) is carried out by serially drilling each of the screw holes and placing the appropriate length (3.5 x 14-15 mm) screw into each of the holes. The locking screw mechanism on the plate is then secured and a lateral cervical radiograph is called for to confirm appropriate levels and instrumentation placement. A medium Hemovac drain is placed in the anterior prevertebral space and brought out through a separate stab incision. Routine closure is then carried out.
2. Posterior Cervical Arthrodesis A longitudinal incision is made in the midline of the posterior neck, directly over the involved spinal level(s). The fascia and muscle are gently divided, exposing the spinous processes and lamina. An x-ray is obtained to confirm the appropriate spinal levels to be fused. A laminectomy and foraminotomy can be performed if necessary. Two (3.5 mm x 14mm) cortical screws ((Vertex (TM) Medtronic, Inc. Minneapolis, MN) are affixed to each lateral mass in the method previous described by Magerl (ref) and connected with a titanium rod on each side of the spine. The bony surfaces and facet joints are then decorticated. One sponge of the BMP/ACS product is placed over the decorticated bone surfaces on each side. The bone removed during the decompresion laminectomy is morsellized and placed in and around the facet joints. The amount of rh-BMP-2 used will be a total of 2.1 mg placed bilaterally, to a total of 4.2mg.
3. Combined Anterior-Posterior Cervical Arthrodesis This surgical procedure combines a posterior cervical decompression and fusion with an anterior cervical fusion. The techniques described for the individual surgical procedures are applicable to the combined Anterior-Posterior procedure. In an anterior-posterior surgery, the amount and positioning of rhBMP-2 will be similar to the anterior surgery (0.525 mg placed anteriorly at each level) or similar to the posterior surgery (2.4 mg across the entire lateral mass on each side posteriorly).

Eligibility criteria: Inclusion Criteria:

* Has cervical spine pathology as noted by neck pain with or without arm symptoms, functional deficit and/or neurological deficit, confirmed by patient history, as well as radiographic imaging studies:

  * CT, MRI scan, x-ray imaging are to include one or more of the following:
  * Instability, as defined by translational motion greater than or equal to 3.5 mm or angular motion greater than 11° at a single segment based upon flexion/extension radiographs.
  * Osteophyte formation.
  * Decreased disc space height.
  * Facet joint degeneration.
  * Disc herniation or protrusion.
  * Signs or symptoms of spinal cord compression (i.e., myelopathy).
* One or more symptomatic levels of degeneration between C3 and C7.
* Age 18 years of age or older at the time of surgery.
* Has not responded to nonoperative treatments including restricted activity, physical therapy, medications, corticosteroid injections, manipulation, TENS for a period of at least three months.
* If female of childbearing age who is not pregnant or nursing and who agrees to use adequate contraception for at least six months following surgery.
* Is willing and able to comply with the study protocol, sign the patient informed consent form, and able to sign the authorization to disclose health information consent form.

Exclusion Criteria:

* Has a condition which requires postoperative medications that interfere with fusion, such as steroids.
* Has been previously diagnosed with osteopenia, osteoporosis, or osteomalacia to a degree that spinal instrumentation would be contraindicated.
* Has active malignancy.
* Has overt or active bacterial infection, either local or systemic.
* Has fever (temperature greater than 101° Fahrenheit oral at the time of surgery).
* Has a documented titanium alloy allergy or allergy to bovine collagen.
* Is mentally incompetent.
* Has a Waddell sign of inorganic behavior score of 3 or greater.
* Is a prisoner.
* Is an alcohol and/or drug abuser, as defined by currently undergoing treatment for alcohol and/or drug abuse.
* Has a history of autoimmune disease.
* Has a hypersensitivity to protein pharmaceuticals, monoclonal antibodies, gammaglobulin, or collagen.
* Has a history of endocrine of metabolic disorder known to affect osteogenesis.
* Is currently pregnant or plans on becoming pregnant within the six months following the surgical procedure

Primary outcomes:
measure: Number of Participants with Serious and Non-Serious Adverse Events
timeFrame: Up to 2 years
Secondary outcomes:
measure: Improvement in patient-reported outcomes
timeFrame: Pre-operative up to 2 years post-operative
Other outcomes:
Locations:
city: Reston
country: United States
facility: Virginia Spine Institute
state: Virginia
Study officials:
affiliation: Virginia Spine Institute
name: Brian R Subach, MD
role: PRINCIPAL_INVESTIGATOR
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