Baxter: Actifuse SHAPE vs DBX in ACC

Background Fusion of the spine was introduced in 1911 for the management of deformity and is
currently used to relieve pain and restore function in patients diagnosed with degenerative
disc disease. Degenerative conditions of the spine resulting in functionally limiting back
pain or neck, and arm pain with or without extremity pain and dysfunction are a major
problem in today's world. Recommended treatment for these conditions can vary initially from
bed rest, exercise, traction, manipulation and drug therapy to eventual surgery.

One of the most common neck conditions that occurs among people older than 50 years is
cervical spondylotic myelopathy (CSM). This may produce symptoms of cervical radiculopathy,
myelopathy, or both. Over time, the normal wear-and-tear effects of aging can lead to a
narrowing of the spinal canal. This compresses or squeezes the spinal cord. CSM can cause a
variety of symptoms, including pain, numbness, and weakness. When patients with degenerative
cervical disease require surgery, an anterior decompression of the neural elements and
reconstruction of the anterior column with allograft, bone graft substitutes or autograft is
common. These types of reconstruction surgery can be referred to as Spinal fusion. The
objective of spinal fusion is to eliminate motion of the vertebral body and thereby relieve
pain.

An anterior cervical corpectomy, fusion and instrumentation, is usually performed for
patients who have pressure on their nerves or spinal cord in their neck. This pressure can
lead to pain, weakness or numbness in the arms and occasionally in the legs as well. If
non-operative treatment such as medications and therapy are ineffective, patients may
require surgery in order to relieve the pressure off their spinal cord and nerves.

Anterior cervical corpectomy (ACC) and fusion is performed for patients with symptomatic,
progressive cervical spinal stenosis and myelopathy. It is performed to remove the large,
arthritic osteophytes (bone spurs) that are compressing the spinal cord and spinal nerves.
However, in order to do so generally involves removing nearly the entire vertebral body and
disc, which must be replaced with a piece of bone graft or bone graft substitute and mended
(fused) together to maintain stability.

Neurosurgeons and orthopedic surgeons are performing bone grafting procedures more
frequently. Surgical applications include treating bone defects, fracture fixation, spinal
fusion and in the revision of failed total joint arthroplasties. According to data collected
by the American Academy of Orthopedic Surgeons, more than 500,000 bone graft procedures are
performed annually in the United States.

The most common source of bone graft used to be autograft, the transfer of a small piece of
the patient's own bone from one site, usually the iliac crest, to another. However, the
amount that can be harvested safely is limited; it increases surgery time and may be
complicated by donor site morbidity. The use of allograft, supplying bone graft from other
patients via bone banks, overcomes these difficulties. However, the demand for allograft now
exceeds the supply, there is a small but finite risk of disease transmission, and it is
highly variable in strength. These factors have led to increasing interest in the use of
synthetic bone graft substitutes.

This study will assess the fusion rates along with the clinical outcomes for the use of
Actifuse Synthetic Bone Graft substitutes mixed with bone marrow aspirate and autograft
mixed with demineralized bone matrix in cervical spine fusion. Actifuse is a synthetic,
porous, silicate-substituted hydroxyapatite and has shown that this maximizes a favorable
bony response.

Study Design This randomized study will be conducted prospectively. The clinical and
radiological outcomes of subjects undergoing anterior cervical corpectomy will be
documented. There will be a total of 40 subjects enrolled, 20 in each arm - Actifuse with
BMA versus autograft with DBM. It is anticipated that the study length will be 42 months
this is based on a recruitment period of 18 months followed by a 24 month post-operative
follow-up period for each patient included in the study. Subjects will be randomized 1:1 per
arm. Randomization will be established at the study site by sealed envelopes accessed at the
time of surgery. The sample size of 40 patients will allow statistical comparison between
the 2 arms based on a postulated fusion rate of 85 %. Given that this is a single center
study with recruitment over 18 months, the total of 40 subjects is a reasonable goal.

Patient Population Subjects enrolled in this study will be identified from the surgeon's
medical practice and will include subjects who have failed conservative treatment and have
been identified by their own physician as requiring anterior cervical corpectomy, fusion and
instrumentation.

Subjects will be suffering from symptoms with the primary diagnosis of cervical spondylotic
myelopathy or cervical spinal stenosis in one to four contiguous levels between C3 and T1.

Data Collection The clinical site's research coordinator or nurse will complete case report
forms. Data will be collected prospectively, after the patient has agreed to participate in
the study by signing the consent form. Data will be collected from the patient's medical
records, departmental based electronic records and radiographic reports to verify
eligibility. Once the patient is verified eligible for the study, data will be collected
from the same sources above. Information will be captured on case report forms. The patient
will also complete questionnaire forms. The information collected will be used for study
analysis results.

Parameters To Be Assessed Demographics, medical history, X-ray results, quality of life
(SF-36), CT Scan results, Concomitant medications, adverse events, pregnancy test, Body Mass
Index (BMI), Concomitant therapies, diagnosis, comorbidities, fusion rate, visual analogue
scale (VAS) for pain, Neck Disability Index (NDI) Questionnaire, Neurological examination
results, clinical assessments and device malfunction, type and duration of surgery, OR room
time, bone graft details, blood loss, length of hospital stay (LOS),return to work, revision
surgeries and complications.

Inclusion Criteria:

- The subject has failed conservative treatment and is a candidate for spinal fusion
surgery.

- The subject is ≥18 years old and of legal age of consent.

- The subject is, in the investigator's opinion, psychosocially, mentally, and
physically able to fully comply with this protocol, including the post-operative
regimen, attend the required follow-up visits, completion of required forms, and be
able to understand and provide written informed consent.

- The subject is skeletally mature (epiphyses closed).

- The subject has voluntarily signed the approved informed consent.

- The subject is willing and able to participate in post-operative clinical and
radiographic follow up evaluations for 2 years.

- No previous surgical intervention at the involved fusion level(s);

- Women of child-bearing potential must not be pregnant or nursing, and agrees to not
get pregnant for 1 year following surgery

Exclusion Criteria:

- Subject has systemic infection or infection at the surgical site.

- Subject has a medical condition that would interfere with post-operative assessments
and care (i.e., metabolic bone disease, neuromuscular disease, autoimmune disease,
active malignancy, psychiatric disease, paraplegia, quadriplegia, etc.).

- Subject has a concurrent disease process that would place the subject in excessive
risk to surgery (i.e. significant circulatory or pulmonary problems, or significant
cardiac disease).

- Subject has a history (present or past) of substance abuse (recreational drugs,
prescription drugs or alcohol) that in the investigator's opinion may interfere with
protocol assessments and/or with the subject's ability to complete the protocol
required follow-up.

- The subject is pregnant/breastfeeding at the time of enrollment, or plans to become
pregnant during the course of the study.

- Subject is participating in another clinical study, which could confound results.

- Subject has ossification of posterior longitudinal ligament (OPLL) at any level

- History of an osteoporotic fracture of the spine, hip or wrist

- History of an endocrine or metabolic disorder (e.g., Paget's disease) known to affect
bone and mineral metabolism

- Taking medications that may interfere with bony/soft tissue healing including chronic
steroid use

- Known allergy to titanium, stainless steels, polyurethane, polyethylene, or ethylene
oxide residuals

- Rheumatoid arthritis or other known autoimmune disease or known to have a systemic
disorder such as HIV, active hepatitis B or C or fibromyalgia

- Severe obesity (Body Mass Index > 40)

- Physical or mental condition (e.g., psychiatric disorder, senile dementia,
Alzheimer's disease, alcohol or drug addiction) that would interfere with patient
self-assessment of function, pain or quality of life.

- Involved in current or pending spinal litigation where permanent disability benefits
are being sought

- Incarcerated at the time of study enrollment

- Diseases that significantly inhibit bone healing (osteoporosis, metabolic bone
disease, uncontrolled diabetes, dialysis dependent renal failure, symptomatic liver
disease)

- Undergoing chemotherapy or radiation treatment, or chronic use of steroids (defined
as more than 6 weeks of steroid use within 12 months of surgery, other than episodic
use or inhaled corticosteroids)

- Subject has severe osteopenia, osteoporosis, osteomalacia, spinal metastases, or
metabolic bone disease that would significantly inhibit bone healing OR the level of
BMD is a T score of -2.5 or below OR patient has sustained a vertebral compression or
nontraumatic hip or wrist fracture.