Clinical trial NCT04650893
Conditions: Dysphagia Dysphonia
Sponsor: University of Nebraska
Start date: 2021-01-02; Completion date: 2023-12-08
Enrollment: 33 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study is to assess the efficacy of intra-operative intravenous non-steroidal anti-inflammatory drug (Ketorolac) versus intravenous (dexamethasone) administration on dysphagia and dysphonia after anterior cervical discectomy and fusion (ACDF).

Detailed description:
The purpose of this study is to assess the efficacy of two intra-operative, intravenous medications on dysphagia and dysphonia following anterior cervical discectomy and fusion (ACDF). The medications include Ketorolac, an anti-inflammatory versus dexamethasone, a corticosteroid. Eligibility criteria includes adults aged 19 years of age or older who are scheduled to undergo a ACDF for radiculopathy or myelopathy. Participants will be recruited for a prospective, randomized, single-blinded clinical drug study and randomized into three cohorts: (1) control (no steroid or non-steroidal anti-inflammatory (NSAID), (2) IV NSAID(1-time dose of 30mg of IV Ketorolac at time of closure), and (3) IV steroid (1-time dose of 10mg of IV dexamethasone at the time of closure. The primary outcome measures are patient questionnaires which include the EAT-10 and Bazaz classification for dysphagia and VHI-10 for dysphonia. In addition, the Neck Disability Index (NDI) and Visual Analogue Pain Scale (VAS) will also be collected. Research follow-up will be subject completed questionnaires to be collected pre-operatively and then post operation at day 1, 3 weeks, 6 weeks, 3 months, 6 months, and 1 year. Post operative questionnaires may be collected at time of patient follow-up in clinic, by phone or mail.

Arms: arm 1: no steroid or non steroidal anti-inflammatory arm 2: one time dose of 30mg of IV Ketorolac at time of closure arm 3: one time dose of 10mg of IV dexamethasone at the time of closure
Interventions: intervention 1: Intravenous Ketorolac intervention 2: Intravenous Dexamethasone intervention 3: Placebo
Intervention descriptions: intervention 1: To assess the efficacy of the meds for dysphagia and dysphonia following ACDF intervention 2: To assess the efficacy of the meds for dysphagia and dysphonia following ACDF intervention 3: Control

Protocol documents:
Prot_SAP_000.pdf: 
Study Protocol and Statistical Analysis Plan 
The Effect of IV NSAID’s and Corticosteroids on Dysphasia and 
Dysphonia Following ASDF 
NCT04650893 
Recent Date of Approval : 1/19/2023 
Study Protocol 
Background & Rationale 
Dysphagia and dysphonia are the most common postoperative complications following anterior cervical 
discectomy and fusion (ACDF). While most postoperative dysphagia and dysphonia is transient, severe 
cases place the patient at risk for malnutrition, aspiration, pneumonia, airway obstruction, persistent 
cough, and death. The reported prevalence of dysphagia varies from 3% to 67% and dysphonia from 1% 
to 51%. The variability is a result of the different ways in which dysphagia and dysphonia are measured 
and defined. There are many different classification systems for dysphagia, the Eating Assessment Tool-
10 (EAT-10) has proven to be reliable, valid, treatment-responsive, and multiculturally versatile. Scores 
of 3 or greater qualify as clinically relevant dysphagia and scores of 15 or greater qualify as severe 
dysphagia, which is associated with a higher risk of aspiration. The Voice Handicap Index-10 (VHI-10) 
has proven to be reliable, valid, and expedient tool to evaluate for dysphonia. Scores greater than 11 
are indicative of clinically significant dysphonia. Recent research suggests that these are appropriate 
patient reported outcome measures (PROMs) to evaluate for dysphagia and dysphonia after cervical 
spine surgery. Local and intravenous (IV) steroids have been shown to reduce dysphagia and 
prevertebral soft-tissue swelling following ACDF. A recent study compared the efficacy of local versus 
intravenous steroids on the likelihood of developing dysphagia and dysphonia after ACDF. It found that 
both yielded better PROMs for dysphagia compared the control group, with a reduced number of 
patients reporting severe dysphagia with local steroid application within the first 2 weeks post-op. 
Local corticosteroids have been associated with impaired wound healing, esophageal complications, 
and pseudoarthrosis, particularly when administered in the retropharyngeal space. In the study 
mentioned above, 2 patients in the local corticosteroid group (out of 29 total) developed 
pseudoarthrosis. Perioperative ketorolac has been shown to have no adverse effect on spinal fusion 
when administered for < 2 days, or for >2 days at a dose of < 120 mg/day. Current standard of care 
processes include both IV or local steroid use as well as no steroid use in decreasing the risks of 
dysphagia or dysphonia post operatively. There are no current specific or routinely used methods in 
using steroid or no steroidal treatments to those receiving this surgical procedure. 
Objectives 
The purpose of this study is to assess the efficacy of intraoperative intravenous nonsteroidal anti-
inflammatory drug (ketorolac) versus intravenous (dexamethasone) administration on dysphagia and 
dysphonia after ACDF. Primary measures for dysphagia include the classification of the Bazaz and EAT-10 
outcome results. The primary measures for Dysphonia will be analyzed by the Voice Handicap Index 
(VHI-10). Secondary measurements include result classification utilizing results from the Neck Disability 
Index(NDI) and Visual Analogue Pain Scale (VAS) for neck pain. Additional measurements to be analyzed 
are comparisons in complication factors in surgical site infection, need for re-operation and 
pseudoarthrosis. 
 


Design 
An on-line randomization generator will be used www.researchrandomizer.org. 
 
Randomization will be an equal split between the three groups with no predictable pattern. The 
subject has a one in three chance of being randomized to any of the three different groups. 
 
Subjects are blinded to the randomization assignment. This is a single blinded study. The treating 
physician and study personnel will know which group the subject is randomized into. 
 
The lead study coordinator will track the randomization assignments, withdrawals and study 
completions. Once 25 from each of the 3 groups have completed the study, the study will cease 
enrollment. 
Methods 
Each study participant will have equal chance of being assigned to one of the three study groups. The 
subjects medical record will be reviewed and the data collected/documented will include: gender, age, 
diagnosis or reason for surgery, co-morbidities, medications, BMI pre-operative and post-operatively. All 
clinic follow-up progress notes will be reviewed to specifically collect any findings documented as 
complications from surgery. 
 
Subjects who elect to consent into the study will be assigned a random study number and randomized 
into three cohorts: control (no steroid or NSAID), IV NSAID (1-time dose of 30 mg of IV ketorolac at the 
time of closure), and IV steroid (1-time dose of 10 mg of IV dexamethasone at the time of closure). 
Randomization schedule will be performed in a 1:1:1 fashion. Patients will be blinded with regard to 
which treatment they received until at least 1 year after surgery.Those subjects whom willingly 
volunteer to be part of the study will be notified promptly if they are found to not meet trial criteria 
and advised that they will be automatically withdrawn from the study. 
 
Patient outcomes (patient completed questionnaires to evaluate for dysphagia and dysphonia) will be 
collected preoperatively and at 1 day (post-surgical day to day 3 post-op), 3 weeks (+/- one week), 6 
weeks (+/- two weeks), 3 months (+/- three weeks), 6 months (+/- one month), and 1 year (+/- three 
months) postoperatively and will include: The Eating Assessment Tool (EAT-10), The Voice Handicap 
Index (VHI-10), Neck Disability Index (NDI), and Visual Analogue Pain Scale (VAS), Bazaz classification 
for dysphagia. 
 
Post operative questionnaire collection will occur at time of outpatient clinic follow-up or subject may 
be called by phone and data collected over the phone or questionnaires mailed if patient preference. 
(Clinic visit follow up per the usual standard of medical care is per the above data collection timeline 
points, however, many times patients are feeling better and do not return for all suggested follow-up). 
Eligibility 
Inclusion 
>/= 19 years of age 
Undergoing ACDF for radiculopathy or myelopathy 
No known allergies or sensitivities to steroid or non-steroidal medications 
This is not an ACDF revision procedure or surgery related to treatment of trauma, infection or tumor. 
 
 


Exclusion 
Procedure is being done for revision, trauma, infection or tumor. 
Patients with known diagnosed metabolic diseases (diabetes, pancreatitis, gout, electrolyte 
imbalances, hypertension, hematological abnormalities including gastrointestinal bleeding...) 
Patients with known kidney disease or a creatinine level above the upper limit of normal > 1.27) (BMet 
labs are completed pre-operatively as standard of care on all patients unless there is documentation of 
normal labs completed within the past 6 months of surgery). 
Patients with known allergy or sensitivities to steroid or non-steroidal medications 
 
Statistical Analysis Plan 
For dysphagia, primary outcome measures will be the Bazaz classification and the EAT-10. For 
dysphonia, primary outcomes will be measured by the VHI-10. Secondary outcomes will be measured 
with Neck Disability Index (NDI), Visual Analogue Pain Scale (VAS) for neck pain. Complications will also 
be documented for comparison to include: surgical site infection, need for reoperation and 
pseudoarthrosis. 
 
Descriptive statistics (specifically counts and percentages) will be computed for all variables to ensure 
data quality and to evaluate the assumptions of statistical tests. Fisher's exact test will be used to 
evaluate associations between treatment groups and categorical measures at each time point. Analysis 
of variance (ANOVA) or the Kruskal-Wallis test, depending on the distribution of the data, will be 
utilized to compare continuous variables between the groups. If the overall p-value from ANOVA is 
statistically significant, pairwise comparisons will be performed and adjusted using Tukey's method. 
Mixed effect models also will be explored, with time, treatment group, and time x treatment group 
interaction terms as fixed effects and with a random intercept term to account for repeated measures 
All tests will be 2-sided and a p-value < 0.05 will be considered statistically significant. 
 
 
No analysis was ultimately completed due to poor follow-up and lack of data.