Project Title An Evaluation of the Effect of the on Post by mikesanye


									Project Title: An Evaluation of the Effect of the _____________      on Post-
               Operative Dysphagia in Patients Undergoing Anterior Cervical Discectomy
               and Fusion

Principal Investigator(s): Douglas Fox, M.D.

Sub-Investigator(s): Mark Burnett, M.D., K. Michael Webb, M.D.

Version: 1.0

Date: September 20, 2010

   I.     Background and Significance

The anterior cervical discectomy and fusion (ACDF) has been an effective surgical
treatment for patients with cervical radiculopathy and myelopathy. 1,2 Though the
procedure is effective in providing favorable clinical results, the complication of post-
operative dysphagia continues to be problematic for many ACDF patients. The incidence
of post-operative dysphagia ranges from 40 – 50% with most exhibiting decreased to full
resolution of symptoms within 6 months post procedure. Severe and disabling dysphagia
is relatively uncommon, but persistent mild to moderate swallowing difficulties lasting
longer in duration than 6 months has a reported incidence between 4 – 17%. 3,4,5

The etiology of dysphagia is non-specific and has been attributed to hematoma, vocal cord
paralysis, biologic agent swelling, pharyngeal plexus denervation, adhesion formation and
plate profile. 6,7 Studies evaluating cervical plate design advocate a design with a lower
and/or smoother profile may provide a viable reduction in the incidence of dysphagia in

________________ has received 5109(k) clearance by the US Food and Drug
Administration (FDA) for use in covering vessels during anterior vertebral surgery. The
shield is a permanent and biocompatible implant that is theorized to potentially minimize
the severity of dysphagia when applied to the surface of the ADCF implant device. It is
thought that the application of the ________________ may minimize tissue attachment to
the surgical site by providing a protective barrier that may reduce the formation of
adhesions or local scar tissue. The reduction of adhesions or local scar tissue may
decrease the incidence of postoperative dysphagia in the ACDF patient.

To date no study has effectively compared the use of _______________ as a means of
decreasing the incidence and/or severity of dysphagia complication in the ACDF surgical

                                        Page 1 of 6
   II.     Specific Aims

This is a prospective, randomized study of 100 subjects undergoing 1 to 3 level
instrumented Anterior Cervical Discectomy and Fusion (ACDF) surgery for degenerative
disk disease (DDD) and/or cervical spondylosis. The overall goal of the study is to:

   1. Compare the incidence and severity of post-surgical dysphagia in ACDF patients
      receiving the _____________ implant (60) against a control (40 subjects) that will
      not receive ______________ implant.

   III.   Subject Selection

a. Inclusion/Exclusion Criteria

Inclusion Criteria
    1. Adults (18 years or older)
    2. Stable health at the time of surgery, based on physical examination and medical
    3. Diagnosed with painful degenerative disc disease or spondylosis of the cervical
       spine, with or without myelopathy and/or neuropathy, requiring elective surgical
       treatment with ACDF at one to three levels
    4. Able to render written informed consent

Exclusion Criteria

   1. Require surgical treatment at more than three levels
   2. Require a corpectomy
   3. History of chronic medical condition, including malignancy, that would render patient
       from completing study
   4. History of previous head or neck injury and/or surgery at the level to be treated
   5. History of dysphagia
   6. History of failed treatment for recreational drug use
   7. Participating in another drug or device clinical trial
   8. Pregnant or may become pregnant during the study
   9. Prisoner
   10. Involved in a Workman’s Compensation or litigation relative to a neck injury

b. Source of subjects and recruitment methods

The primary source of subjects will be recruited from _____________ neurosurgical

   IV.    Subject Enrollment

a. Methods of Enrollment

Patient referrals from _____________ will be directed to a Research staff contact.
Preliminary discussions may take place in person or by telephone at which time research
staff will inform the subject of the study goals and risks.
                                            Page 2 of 6
b. Procedures for obtaining informed consent

Upon determination of their eligibility, patients and their families/guardians will be provided
the informed consent forms and the extent of the research will be fully explained both
orally and in writing. Once subject acknowledges full understanding of the study, they will
be invited to sign the informed consent.

c. Treatment assignment/randomization

Subjects will be randomized to one of two groups on a 1:1 ratio.

   V.     Study Procedure

General Procedures

For this initial study, 100 patients scheduled for anterior cervical discectomy and fusion
(ACDF) will be screened for eligibility by participating physicians. Research staff will be
contacted by physician office to further discuss the study informed consent with the
subject. Upon verbalized understanding of the risks and benefits of the study, the subject
will be invited to participate. Each subject will be given a unique identification number to be
used in lieu of their PHI.

Research staff will randomize subjects to one of two groups.

   1. Group one will be comprised of ACDF subjects who receive the addition of the
      ______________ during their procedure.
   2. Group two will be comprised of ACDF subjects without the addition of the
      ______________. This group will serve as the control with standard of care for the
      ACDF procedure.

All study pre, intra and post-surgical assessment data, along with any medical records or
subject private health information will remain in a password-protected computer, using the
latest encryption, and located behind locked doors within the research office. Only those
research staff participating in this study will have access to the data.

Neurosurgical Procedure

Subject will undergo standard ACDF procedure. The actual surgical procedure will not be
altered in any way for enrolled subjects. After the insertion of the interbody fusion device,
bone graft material, and the surgical plate have been implanted, those subjects
randomized to receive the ___________ will have the shield placed over the surgical site
and trimmed for sizing before implantation. Once sizing complete, the shield will be
attached by suture to the surrounding soft tissue per manufacturer’s Instructions for Use
(see addendum). No drain will be inserted at the end of the procedure for either study

                                          Page 3 of 6
Pre-Operative Assessments

Before the surgical procedure, the research staff will acquire the following data and survey
results for each subject:
              Medical history
              SF-12v2 Health Questionnaire
              Neck Disability Index Score (NDI)
              Mann Assessment of Swallowing Ability (MASA)
              Age, gender, weight, BMI
              Concomitant diseases
              Current medications

Intra-Operative and Inpatient Stay Assessments

                 Notation of ACDF levels treated; one or two
                 Type/duration of retraction-static versus dynamic retraction
                 Method of surgical procedure – e.g.: Smith-Robinson technique
                 Endotracheal cuff pressure (ETCP)
                 Type/size of intervody device used
                 Type of internal fixation used
                 Quantity and type of graft materials used
                 Timed length of surgery
                 Estimated blood loss
                 Type of neck immobilization – e.g.: type of bracing utilized
                 Imaging (CT or MRI) before discharge from inpatient stay
                 Length of hospital stay

Post-Operative Assessments

Subjects will follow-up with research staff physician at six (6) weeks, three (3) months, six
(6) months and twelve (12) months. Refer to Table 1 for schedule of assessments:

Table 1

                          Visit #1            Visit #2             Visit #3              Visit #4
Assessments            6 Weeks ± 1 Week   3 Months ± 2 Weeks   6 Months ± 3 Weeks   12 Months ± 6 Weeks

Physical Exam
                              X                   X                    X
  1. SF-12v2                                                                             NDI only
  2. NDI                      X                   X                    X
  3. MASA
Imaging (CT or MRI)           X                                        X

                                             Page 4 of 6
   VI.     Biostatistical Analysis

Differences in postoperative incidence of dysphagia will be assessed between the
________________ treated and control groups using separate paired t-tests.

Several of the dependent variables will be analyzed using a 2-way ANOVA with repeated
measures on the factors of dysphagia treatment and time-interval. Dysphagia treatment
has two levels (_________________treated and control), while the number of levels in
time-interval varies with the outcome measure: swallowing ability has 6 time-intervals. The
incidence of clinically significant dysphagia will be compared between the
_______________________ treated and control groups using Fisher’s exact test. The
significance level of all statistical tests will be = 0.05.

   VII.    Risks and Discomforts

The use of the ______________ in an ACDF procedure is a new investigational implant,
and though no adverse effects are expected, it is possible that unexpected side effects
may occur. All known risks involved with the ACDF procedure and the HydroFix Vaso
Shield™ will be explained prior to subject signing the surgical consent before surgery.

Participation in this study will require collection of protected health information (PHI).
Every effort will be made to keep this information secured. The potential unanticipated
disclosure of this information does carry a small but potential risk of discrimination that
could affect employability or insurability, social stigma, or other unpredicted repercussions.

   VIII.   Potential Benefits

The potential benefit for the _______________ treated cohort may be decreased
incidence of dysphasia symptoms, but this potential benefit has not been demonstrated
and is the focus of this study.

   IX.     Ethical Considerations

The study will be conducted in accordance with the U.S. Food and Drug Administration’s
(FDA) Code of Federal Regulations (CFR 21), and Good Clinical Practice (GCP) guidelines.

   X.      References

   1. Gore DR, Sepic SB. Anterior discectomy and fusion for painful cervical disc disease. A report of 50
      patients with an average follow-up of 21 years. Spine 1998;23:2047-51.

   2. Bohlman HH, Emery SE, Goodfellow DB, Jones PK. Robinson anterior cervical discectomy and
      arthrodesis for cervical radiculopathy. Long-term follow-up of one hundred and twenty-two patients. J
      Bone Joint Surg Am 1993;75:1298-307.

   3. Segebarth B, Datta JC, Darden B, Janssen ME, Murrey DB, Rhyne A, Beckham R, Ponce C.
      Incidence of dysphagia comparing cervical arthroplasty and ACDF. SAS Journal 2010;4:3-8.

                                               Page 5 of 6
4. Bazaz R, Lee MJ, Yoo, JU. Incidence of dysphagia after anterior cervical spine surgery: a
   prospective study. Spine 2002;27:2453-8.

5. Riley LH III, Skolasky RL, Albert TJ, Vaccaro AR, Heller JD. Dysphagia after anterior cervical
   decompression and fusion: prevalence and risk factors from a longitudinal cohort study. Spine

6. Fountas KN, Kapsalaki EZ, Nikolaskakos LG, et al. Anterior cervical discectomy and fusion
   associated complications. Spine 2007;32:2310-7.

7. Smucker JD, Rhee JM, Singh K, Yoon ST, Heller JG. Increased swelling complications associated
   with off-label usage of rhBMP-2 in the anterior cervical spine. Spine 2006;31:2813-9.

8. Lee MJ, Bazaz R, Furey CG, Yoo J. Influence of anterior cervical plate design on Dysphagia: a 2-
   year prospective longitudinal follow-up study. J Spinal Disord Tech 2005;18:406-9.

                                            Page 6 of 6

To top