A Prospective, Randomized Controlled Trial on the Effect of Local Steroid Application on a Cervical Plate Versus Intravenous Steroids on Dysphagia Following Anterior Cervical Discectomy and Fusion (ACDF)
Phase: NA
Conditions: Cervical Spine
Sponsor: Northwestern University

 
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A SINGLE BLIND, PROSPECTIVE, RANDOMIZED CONTROLLED TRIAL ON THE 
EFFECT OF LOCAL STEROID APPLICATION VERSUS INTRAVENOUS STEROIDS 
ON DYSPHAGIA FOLLOWING ANTERIOR CERVICAL DISECTION AND FUSION  
 
 
PRINCIPAL INVESTIGATOR:  
Alpesh A. Patel, MD, FACS 
 
Jason Savage, MD 
 
676 N. St. Clair, Suite 1350 
 
312-695-7540 
 
312-926-4643 
 
alpesh.patel@nm.org 
 
SUB-INVESTIGATORS: 
Rueben Nair, MD 
 
Northwestern University 
 
 
 
 
 
Wellington Hsu, MD 
 
Northwestern University 
 
 
 
Dr. Raymond Hah, MD 
 
University of Wisconsin-Madison 
 
 
Dr. Leo Spector, MD 
 
OrthoCarolina Research Institute 
 
 
PARTICIPATING SITES: 
Northwestern Memorial Faculty Foundation 
(NMFF) 
 
675 N. St. Clair, Suite 17-100 
 
Chicago, IL 60611 
 
312-695-6800 
 
 
 
Northwestern University (NU) 
 
676 N. St. Clair, Suite 1350 
 
Chicago, IL 60611 
 
 
 
OrthoCarolina Research Institute 
 
001 Vail Avenue, Suite 300 
 
Charlotte, NC 28207 
 
 
 
University of Wisconsin-Madison 
 
 
FUNDING AGENCY: 
 
Cervical Spine Research Society (CSRS) 
 
 
 
 
Synopsis 

 
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Title 
A single blind, prospective, randomized controlled trial on the effect of 
local steroid application versus intravenous steroids on dysphagia 
following anterior cervical discectomy and fusion (ACDF) 
Short Title 
Effect of local application vs. IV steroids on dysphagia after ACDF 
Protocol Date 
12/14/2015 
Study Duration 
2 years 
Study Center(s) 
Northwestern Memorial Faculty Foundation (NMFF), Northwestern 
University (NU), University of Wisconsin-Madison, OrthoCarolina 
Research Institute 
Objectives 
Local application of steroids in ACDF surgery will lead to decreased 
incidence of dysphagia compared to intravenous steroids or a control 
group 
Number of Subjects 
85 (randomized to group I (control group), group II (10 mg of 
intraoperative intravenous decadron), or group III (40mg of 
triamcinolone placed on cervical plate), i.e. 25 per group. 
Diagnosis and Main 
Inclusion Criteria 
Patients undergoing ACDF (single or multi-level) for the treatment of 
radiculopathy or myelopathy by Drs. Hsu, Patel, and Savage. 

 
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TABLE OF CONTENTS 
Synopsis ...........................................................................................................................................2 
 
1.0  Introduction .............................................................................................................................4 
 
2.0  Study Objectives...................................................................................................................4,5 
 
3.0  Selection of Subjects ...............................................................................................................5 
3.1  Inclusion Criteria ...................................................................................................................5 
3.2  Exclusion Criteria ..................................................................................................................5 
 
4.0  Subject Registration................................................................................................................5 
 
5.0  Study Design & Methods .....................................................................................................5,6 
 
6.0  Statistical Plan .........................................................................................................................6 
 
7.0  Data Collection & Record Keeping .......................................................................................6 
 
8.0  References ................................................................................................................................7 
 
Appendices ......................................................................................................................................8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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1.0 
INTRODUCTION - BACKGROUND AND RATIONALE  
Dysphagia is a common complication after ACDF.1  PSTS is also a natural sequela of 
ACDF and can lead to airway compromise among other complications.2  Previous studies 
have demonstrated that administration of intravenous methylprednisolone (1mg/kg) after 
anterior cervical spine surgery reduced the incidence of pharyngolaryngeal lesions as 
identified by nasofibroscopic examination.3  Lee et al. prospectively evaluated 50 patients 
and determined that local application of steroids in the retropharyngeal area following 
ACDF reduced PSTS and odynophagia as measured by the Visual Analogue Scale (VAS) 
and the Neck Disability Index (NDI) compared to a control group.4  Furthermore, there 
were no adverse events/reactions from local application of steroid on a gel foam sponge 
in the setting of anterior spinal surgery.  There are no studies in the current literature that 
investigate the incidence of dysphagia with application of local steroids after ACDF, nor 
are there any studies that stratify the efficacy of local steroids compared to intravenous 
steroids. There is also no current spine literature that directly compares the efficacy of 
intravenous steroids versus local steroids in the incidence of dysphagia or dysphonia.  
Our study will be the first in the literature to assess the efficacy of local steroids in 
reducing the incidence of dysphagia after anterior cervical spine surgery, and as a result, 
may improve patient outcomes after ACDF. 
 
Dysphagia and dysphonia are common complications after anterior cervical spine 
surgery.1 Despite their clinical importance, studies on the treatment and/or prevention of 
these complications are limited due to the lack of valid and reliable outcome measures. 
The majority of research is found in the otolaryngology literature and has focused on 
disease pathophysiology, diagnosis, and therapy.   
 
The Bazaz score has been used in the spine literature to evaluate dysphagia after anterior 
cervical discectomy and fusion (ACDF).5 This is a subjective questionnaire that has not 
been validated in the literature.  Additionally, new patient-centered outcome measures, 
the Eating Assessment Tool (EAT-10) and Voice Handicap Index (VHI-10) have recently 
been developed, and in addition to the Bazaz score, have been shown to have excellent 
validity and reliability in the ENT patient population.6 These instruments can be used to 
document the initial dysphagia or dysphonia severity and monitor the treatment response 
in people with a wide array of swallowing and voice disorders.   
 
2.0 
OBJECTIVES 
 To determine if the use of steroids decreases the incidence of dysphasia after 
anterior cervical discectomy and fusion (ACDF).   
 If steroids are useful, determine which method of steroid administration is most 
efficacious (IV versus local application).   
 We hypothesize that local application of steroids in ACDF surgery will lead to a 
decreased incidence of dysphagia, in the postoperative period as compared to 
intravenous steroids or a control group. 
 To evaluate the incidence of dysphonia, as measured by the Voice Handicap 
Index (VHI-10), as well as other validated outcome measures (NDI, VAS, EQ-
5D).  
  

 
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3.0 
SELECTION OF SUBJECTS 
 
3.1 
INCLUSION CRITERIA: 
 All patients undergoing ACDF (single or multi-level) for the treatment of 
cervical radiculopathy or myelopathy with Drs. Hsu, Patel, and Savage. 
 All subjects must have given signed, informed consent prior to registration on 
study. 
  
 
3.2 
EXCLUSION CRITERIA 
 Patients undergoing revision surgery, any operations for trauma, infection, 
tumor 
 Patients with general metabolic diseases such as rheumatoid arthritis, diabetes, 
chronic heart and renal diseases.   
 
4.0 
SUBJECT REGISTRATION  
The subjects will be recruited by the PI, co-investigators, or authorized study staff at the 
orthopaedic surgery clinic or prior to their ACDF surgery in the pre-operative hold area 
in. The study will be reviewed with the subjects and they will be consented by the PI, co-
investigator, or other authorized study staff. 
 
Each collaborating site will be involved in subject recruitment, consent, and all data 
collection for any patients that are enrolled in the study at each respective site. 
 
5.0 
STUDY DESIGN & METHODS 
We intend to prospectively evaluate 85 patients as part of a single blind, randomized 
controlled study.  Subjects would be randomized to group I (control group, no steroid), 
group II (10 mg of intraoperative intravenous decadron with gel foam sponge placed on 
cervical plate), or group III (40mg of triamcinolone on gel foam sponge dabbed on the 
anterior cervical plate).  Subjects will be blinded to the treatment arm.  Randomization 
will take place on the day of surgery.  85 envelopes will be sealed, 25 of which will 
contain a document specifying “control”, “iv steroids”, or “steroid sponge”.  The 75 
envelopes will then be shuffled to create a random assortment.  The circulating nurse in 
the OR will at random choose one envelop prior to the start of the operative procedure.  
This will in turn specify the treatment group for each patient. 
 
There is no standard of care regarding the use of IV or local steroids in the setting of 
ACDF.  Currently, the use of either IV or local steroids is at the discretion of the 
attending surgeon.  To my knowledge, there are several spine surgeons at our institution 
that currently use no steroid, and others who use a combination of IV and/or local 
steroids.      
The primary outcome measure is the incidence of dysphagia as measured by Eating 
Assessment Tool (EAT-10) and the Bazaz score.  The patients will prospectively fill out 
these surveys preoperatively, post-operative day 1, week 2, week 6, month 3, month 6, 
and 1 year as a measure of dysphagia.    The standard of care is to see patients in the 
office at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year after surgery, and therefore, 
no extra visits will be necessary for this study.  X-rays will be taken at 6 weeks, 3 

 
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months, and 12 months post-op, which is the current standard of care.  No additional x-
rays will be obtained.   
 
A secondary outcome measure will be the incidence of dysphonia, as measured by the 
Voice Handicap Index (VHI-10), as well as other validated outcome measures (NDI, 
VAS, EQ-5D).  The questionnaires will take approximately 20 minutes to complete and 
will be administered in the hospital, during the post-operative clinic visits with the 
surgeon, or over the phone. The surgeons will also listen to the patient’s voice at these 
different time points and comment on dysphonia as being absent, mild, moderate, or 
severe.  
 
Additionally, a chart review will be performed from11/01/2013 to 12/30/2016 from NMH 
Medical records (PRIMES, Cerner PowerChart) and NMFF Medical Records (EpicCare, 
IDX/GE Centricity) to obtain the following data: Complications such as infection, post-
operative hematoma, airway compromise, and recurrent laryngeal nerve palsy. All data 
collected from chart review will be de-identified and noted on the Data Collection Form. 
Each subject will be assigned a study number and all data will be linked to that number 
using the Coded Identifier List. The PI will identify which charts will be reviewed. The 
chart review will be performed by the PI, co-investigators, or authorized study 
coordinator.  
 
There are potential physical risks from being in this study.  The use of steroids may have 
an adverse effect on wound healing and/or transiently elevate blood sugar.  There have 
been no documented wound complications from using either IV or local steroids in the 
setting of ACDF.  Furthermore, we purposely excluded patients with a history of diabetes 
or other endocrine disorder in an attempt to minimize this potential side-effect or 
complication. Another possible risk related with participation in this study is the loss of 
privacy. To reduce these risks, all of the information collected will be de-identified and 
stored in a password protected file on a password protected computer. Additionally, some 
of the questions asked in the surveys may be upsetting, or the subject may feel 
uncomfortable answering them. If the subject does not wish to answer a question, they 
may skip it and go to the next question. 
 
6.0 
STATISTICAL PLAN  
We will use T score or ANOVA to compare EAT-10 scores, VHI scores, andEQ-5D, and 
Chi square for subjective findings.  The P value will be set at 0.05. 
 
A power analysis was performed to determine the sample size needed.  Based on 
previous studies evaluating the EAT-10 in normal patients and those with dysphasia the 
analysis concluded: with total sample size 85 (Group I: 25, Group II: 25, Group III: 25) 
and estimated standard deviation of EAT-10 as 12.7, power = 0.92 
 
Drs. Savage, Patel, and Hsu, perform approximately 6 ACDFs a month. This would allow 
us to collect our proposed sample size in approximately 12-14 months. 
 
7.0 
DATA COLLECTION & RECORD KEEPING 

 
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All information regarding the nature of the proposed investigation provided to the 
investigator (with the exception of information required by law or regulations to be 
disclosed to the IRB, the subject, or the appropriate regulatory authority) will be kept in 
confidence by the investigator. All personal information will be treated as strictly 
confidential and not made publicly available.  All records and appendices are stored in 
separate locked filling cabinets as well as a password protected computers which are 
accessed only by the Principal Investigator, co-investigator, and authorized study staff. 
All identifiable data will be destroyed a year after the study is complete. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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9.0 
REFERENCES  
 
1. Fountas KN, Kapsalaki EZ, Nikolakakos LG, et al. Anterior cervical discectomy and fusion 
associated complications. Spine, Oct 2007; 32(21):2310-7 
 
2. Sanfillipo JA Jr, Lim MR, Jacoby SM, et al. “Normal” prevertebral soft tissue swelling 
following elective anterior cervical decompression and fusion.  J Spinal Disord Tech, Aug 2006; 
19(6):399-401 
 
3. Pedram M, Castagnera L, Carat X, et al. Pharyngolaryngeal lesions in patients undergoing 
cervical spine surgery through the anterior approach: contribution of methylprednisolone.  Eur 
Spine J, Feb 2003;12(1):84-90 
 
4. Lee SH, Kim KT, Suk KS, et al. Effect of retropharyngeal steroid on prevertebral soft tissue 
swelling following anterior cervical discectomy and fusion: a prospective, randomized study. 
Spine, Dec 2011;36(26):2286-92 
 
5. McAfee PC, Cappuccino A, Cunningham BW, et al. Lower incidence of dysphagia with 
cervical arthroplasty compared with ACDF in a prospective randomized clinical trial. J Spinal 
Disord Tech, Feb 2010;23(1):1-8 
 
6. Belafsky PC, Mouadeb DA, Rees CJ, et al. Validity and reliability of the Eating Assessment 
Tool (EAT-10).  Ann Otol Rhinol Laryngol, Dec 2008; 117(12);919-24 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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APPENDICES 
 
CODED IDENTIFIER FORM 
 
Unique subject identifier 
Last 
Name 
First Name 
MRN 
1 
 
 
 
2 
 
 
 
3 
 
 
 
4 
 
 
 
5 
 
 
 
6 
 
 
 
7 
 
 
 
8 
 
 
 
9 
 
 
 
10 
 
 
 
11 
 
 
 
12 
 
 
 
13 
 
 
 
14 
 
 
 
15 
 
 
 
16 
 
 
 
17 
 
 
 
18 
 
 
 
19 
 
 
 
20 
 
 
 
21 
 
 
 
22 
 
 
 
23 
 
 
 
24 
 
 
 
25 
 
 
 
26 
 
 
 
27 
 
 
 
28 
 
 
 
29 
 
 
 
30 
 
 
 
31 
 
 
 
32 
 
 
 
33 
 
 
 
34 
 
 
 
35 
 
 
 
36 
 
 
 
37 
 
 
 
38 
 
 
 

 
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Unique subject identifier 
Name 
MRN 
Number 
Telephone Number 
39 
 
 
 
40 
 
 
 
41 
 
 
 
42 
 
 
 
43 
 
 
 
44 
 
 
 
45 
 
 
 
46 
 
 
 
47 
 
 
 
48 
 
 
 
49 
 
 
 
50 
 
 
 
51 
 
 
 
52 
 
 
 
53 
 
 
 
54 
 
 
 
55 
 
 
 
56 
 
 
 
57 
 
 
 
58 
 
 
 
59 
 
 
 
60 
 
 
 
61 
 
 
 
62 
 
 
 
63 
 
 
 
64 
 
 
 
65 
 
 
 
66 
 
 
 
67 
 
 
 
68 
 
 
 
69 
 
 
 
70 
 
 
 
71 
 
 
 
72 
 
 
 
73 
 
 
 
74 
 
 
 
75 
 
 
 
 
 
 
 
 
 

 
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DATA COLLECTION FORM 
 
Unique subject 
identifier 
Infection 
Post-
operative 
hematoma 
Airway 
compromise 
Recurrent 
laryngeal 
nerve palsy 
1 
 
 
 
 
2 
 
 
 
 
3 
 
 
 
 
4 
 
 
 
 
5 
 
 
 
 
6 
 
 
 
 
7 
 
 
 
 
8 
 
 
 
 
9 
 
 
 
 
10 
 
 
 
 
11 
 
 
 
 
12 
 
 
 
 
13 
 
 
 
 
14 
 
 
 
 
15 
 
 
 
 
16 
 
 
 
 
17 
 
 
 
 
18 
 
 
 
 
19 
 
 
 
 
20 
 
 
 
 
21 
 
 
 
 
22 
 
 
 
 
23 
 
 
 
 
24 
 
 
 
 
25 
 
 
 
 
26 
 
 
 
 
27 
 
 
 
 
28 
 
 
 
 
29 
 
 
 
 
30 
 
 
 
 
31 
 
 
 
 
32 
 
 
 
 
33 
 
 
 
 
34 
 
 
 
 
35 
 
 
 
 
36 
 
 
 
 
37 
 
 
 
 
38 
 
 
 
 
39 
 
 
 
 

 
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Unique subject 
identifier 
Infection 
Post-
operative 
hematoma 
Airway 
compromise 
Recurrent 
laryngeal 
nerve palsy 
40 
 
 
 
 
41 
 
 
 
 
42 
 
 
 
 
43 
 
 
 
 
44 
 
 
 
 
45 
 
 
 
 
46 
 
 
 
 
47 
 
 
 
 
48 
 
 
 
 
49 
 
 
 
 
50 
 
 
 
 
51 
 
 
 
 
52 
 
 
 
 
53 
 
 
 
 
54 
 
 
 
 
55 
 
 
 
 
56 
 
 
 
 
57 
 
 
 
 
58 
 
 
 
 
59 
 
 
 
 
60 
 
 
 
 
61 
 
 
 
 
62 
 
 
 
 
63 
 
 
 
 
64 
 
 
 
 
65 
 
 
 
 
66 
 
 
 
 
67 
 
 
 
 
68 
 
 
 
 
69 
 
 
 
 
70 
 
 
 
 
71 
 
 
 
 
72 
 
 
 
 
73 
 
 
 
 
74 
 
 
 
 
75