Clinical trial NCT03241030
Conditions: Herpangina Gingivostomatitis Hand, Foot and Mouth Disease
Sponsor: University of Texas at Austin
Start date: 2017-09-12; Completion date: 2019-06-20
Enrollment: 102 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to see if sucralfate, a medication commonly used for patients with stomach ulcers, may help pediatric patients with mouth ulcers decrease their pain level and improve their ability to drink.

Detailed description:

Arms: arm 1: Subjects will receive sucralfate arm 2: Subjects will receive a placebo
Interventions: intervention 1: Sucralfate intervention 2: Placebo intervention 3: Acetaminophen intervention 4: Ibuprofen
Intervention descriptions: intervention 1: Will receive 20mg/kg/dose up to 1 gram. intervention 2: Will received placebo solution of similar quantity to that of the weight based dose of sucralfate. intervention 3: All patients will receive analgesia, either acetaminophen 15mg/kg or ibuprofen 10mg/kg depending on medication administration prior to arrival in the Emergency Department and at the discretion of the treating physician, in addition to either the experimental drug or placebo. intervention 4: All patients will receive analgesia, either acetaminophen 15mg/kg or ibuprofen 10mg/kg depending on medication administration prior to arrival in the Emergency Department and at the discretion of the treating physician, in addition to either the experimental drug or placebo.

Protocol documents:
Prot_SAP_002.pdf: 
 
 
 
 
Sucralfate to Improve Oral Intake in Children with Infectious Oral Ulcers: A Randomized, 
Double-blind, Placebo-Controlled Trial 
 
NCT Number: 2017-06-0024 
 
Date of Document: 07-31-2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


I. 
Objectives/Hypothesis 
Specific Aim 1: To evaluate comparative effectiveness of sucralfate versus placebo on the 
improvement of oral fluid intake (in ml/kg) 60 minutes post administration in children between 
6 months and 5 years of age with oral infectious ulcers presenting to an urban pediatric 
emergency departments with concern for decreased oral intake or dehydration.   
 
Hypothesis: Sucralfate will lead to a clinically significant improvement in oral intake 
relative to placebo in pediatric patients diagnosed with oral infectious ulcers and a history 
consistent with poor oral intake or dehydration presenting to the emergency department.  
 
Specific Aim 2: To explore the difference in the rates of intravenous fluid (IVF) administration, 
admission rates, ED length of stay, rates of unscheduled visits and physician perception of 
adequate oral intake in children between 6 months and 5 years with oral infectious ulcers treated 
with sucralfate versus placebo.  
Hypothesis: Pediatric patients receiving sucralfate will have decreased rates of IVF 
administration, hospital admission, unscheduled return visits, as well as shorter ED length of stay 
compared to the placebo group.  
 
II. 
Methods 
Study Design and Setting 
The study will take place in an urban pediatric ED with approximately 80,000 visits per year, of 
which about 700 visits per year are due to oral infectious ulcers. This study will be a double-blind, 
randomized, placebo controlled trial comparing sucralfate to placebo for improving oral intake 
in children with oral ulcers. Due to lack of benefit from clinical trials, and the potential for harm, 
placebo was chosen as a comparator over combination diphenhydramine, aluminum hydroxide, 
and lidocaine. A randomized control trial will be the best study to determine efficacy of the 
therapy, while minimizing bias.   
 
Selection of Participants 
This will be a convenience sample based on study staff availability. Subjects will be identified in 
triage based on a history of oral ulcers or by physicians during examination. They will be screened 
and enrolled by a member of the study team.  
 
Subject Eligibility:  
Inclusion: 
Age ≥6 months and <5 years of age 
Present with oral infectious ulcers such as gingivostomatitis, herpangina, or hand, foot 
and mouth disease 
History of poor oral fluid intake by parent or guardian  
English or Spanish speaking parents or guardians 
Exclusion: 
Severely dehydrated or toxic, requiring immediate resuscitation  
Exclusively Breastfed 
Dental disease 
Mouth trauma 


Active Malignancy 
Preexisting upper airway obstruction or swallowing difficulties 
Received IVF within 24 hours 
Administration of BOTH acetaminophen AND ibuprofen within 4 hours of enrollment 
 
Interventions 
After consent is obtained from the parents or guardians, study patients will be randomized to 
receive treatment with either the experimental drug (sucralfate) or placebo. Simple 
randomization allocation will be performed with a computerized randomization process. The 
research pharmacy will maintain a treatment arm allocation key. The pharmacist will send an 
amber colored syringe with a number and no other identifying factors. This will blind patients, 
family, nurses, physicians and study staff from the assignment. 
 
Subsequently, the study personnel will collect baseline data from the patient’s guardian. Data 
will be recorded on a standardized form and will include subject demographics (including age, 
ethnicity, and sex), historical information about prior analgesia at home (medication, dose and 
time prior to arrival), duration of current symptoms, an initial set of vital signs (temperature, 
heart rate, blood pressure and peripheral pulse oximetry), and the baseline clinical dehydration 
score. The Clinical Dehydration Score (CDS) will be used since prior research exhibited moderate 
inter-observer reliability(23) and it has been previously validated for the evaluation of 
dehydration(24-26).  
 
All patients will receive analgesia, either acetaminophen 15mg/kg or ibuprofen 10mg/kg 
depending on medication administration prior to arrival in the ED and the discretion of the 
treating physician. Some patients may receive these medications in triage if they are febrile, the 
rest of the participants will receive analgesia as part of the study protocol.  
 
Patients randomized to the experimental arm will receive therapy with oral sucralfate. 
Administration will be by the treating nurse using a measured syringe provided by the pharmacy 
to the oral cavity, aiming to cover the inflamed mucosa and ulcerative lesions. Given the young 
nature of the patients in the study, the swish and swallow method is not feasible. A weight based 
dose of sucralfate will be administered - 20mg/kg/dose up to 1g, consistent with published 
recommendations for other indications (27). Studies have shown doses from 15-50mg/kg/dose 
to be relatively safe in the pediatric population(15-17). If a patient spits the medication out within 
5 minutes of administration, the dose will be re-administered.  
 
Patients randomized to the placebo arm will receive therapy with a solution of water and ora-
sweet syrup. Using prepared syringes from the pharmacy, the nurses will administer a placebo 
volume that will be equivalent to the volume of the weight based sucralfate suspension.                           
Ora-sweet syrup is essentially a sweet base, normally used as a vehicle for other pediatric 
suspension medications. The ingredients glycerin, sorbitol, sodium saccharin, xanthan gum, 
flavoring, buffered with citric acid, sodium citrate and preservatives provide a solution similar in 
color, taste, and smell. Both will be dispensed in amber syringes to conceal any minor differences 


in appearance. Similar ingredients have been used in other studies as placebo, and have not 
impeded the ability to demonstrate efficacy of sucralfate(3, 19).  
 
After the administration of the study drug, subjects will be actively encouraged to drink fluids. 
The study staff or nursing staff will provide oral hydration supplements in the form of age 
appropriate formula or pedialyte (instead of breastfeeding), apple juice, Gatorade or popsicles. 
The study staff will have a script of instructions explaining to the family the importance of 
encouraging oral intake with small sips every few minutes, which is the current standard of care 
at our institution. The study staff or nurses will check in at 30 minutes post administration to 
make sure parents are trialing fluids and offer alternative fluids if patient prefers.  
 
At 60 minutes post administrations, the study staff will document the volume of the fluids in ml. 
Fluid amount ingested will be measured by research staff according to calculated measurements 
of cups, other containers, and syringes in the ED or packaged frozen rehydration solution. In 
addition, they will record the dose and timing of analgesia provided in the hospital, an updated 
set of vital signs (temperature, heart rate, blood pressure and peripheral pulse oximetry), and 
any side effects. Physicians will be asked if they feel the oral intake is sufficient per their 
impression. Both the treating physician and parent/guardian will be asked their best guess of 
treatment allocation to assess the adequacy of blinding.  
 
Following completion of the experimental stage as detailed above, patients will be released to 
receive standard of care therapy as determined by the assigned attending ED physician. After the 
patient is discharged from the ED, study staff will record the need for further IV hydration, ED 
length of stay, the final disposition, and whether or not a prescription for sucralfate is provided. 
The research nurse will contact each family approximately 72 (72-96) hours after initial visit to 
inquire about unscheduled visits elsewhere, and ED records will be reviewed for any unscheduled 
return visits. 
 
Methods of Measurement and Outcome Measures 
The primary outcome will be the amount of fluid ingested within 60 minutes of administration of 
the study drug, expressed in milliliters per kilogram.  
 
The secondary outcomes measured will include (1) whether the oral intake is deemed adequate 
at 60 minutes (as determined by the treating clinician); (2) whether patient required fluid 
administration by intravenous line (oral hydration failure); (3) whether participant required 
hospital admission; (4) duration of stay in the ED; (5) incidence of unscheduled visits. 
 
Sample Size 
The treatment groups will be analyzed on an intention-to-treat basis. The only prior study in the 
literature with a similar endpoint of fluid intake between 2 treatment groups (viscous lidocaine 
versus placebo) with oral infectious ulcers demonstrated a baseline fluid intake rate of 8.4 ml/kg, 
mean difference of 4.3ml/kg and SD 7ml/kg ingested during a 60-minute fluid trial. A panel of 
experts convened for the study design deemed an effect size of 4 ml/kg to be clinically 
meaningful(12). Using this data, with an alpha of 0.05 and beta of 0.20, sample size calculations 


yield n=50 per group (100 total). No allowance is made for loss to follow-up because of the short 
timeframe of this study. The calculations were performed using STATA (version 13.0; Statacorp, 
College Station, TX).  
 
Statistical Analysis 
 
Baseline group characteristics will be summarized in a table with means and standard deviations 
for continuous data, percentages for categorical data, and medians with interquartile ranges for 
ordinal data.   
 
The primary outcome of oral fluid intake in milliliters per kilogram will be compared between the 
two groups using a two-tailed t-test, or non-parametric equivalent if the data is non-normally 
distributed. The data will be presented with mean intake in each group and its standard 
deviation, with comparison between the groups presented as a difference in means and its 95% 
confidence interval, and resultant p value. 
 
Secondary outcomes for this study will include IVF administration rates, hospital admission rates, 
ED LOS, rates of unscheduled visits, and physician perception of adequate oral intake. Analysis of 
these variables will be completed using appropriate statistical analysis depending on the nature 
of the data (t-test for continuous, chi square of Fisher’s exact test for categorical, and Mann-
Whitney U test for ordinal). Non-parametric tests will be used when appropriate. 
 
Finally, if significant baseline difference in the groups occur, linear multivariable regression 
analysis of the primary endpoint will be performed to adjust for potential confounders.