Clinical trial NCT03705273
Conditions: Asthma Croup
Sponsor: Vanderbilt University Medical Center
Start date: 2018-10-23; Completion date: 2020-10-02
Enrollment: 40 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Study of the palatability and acceptability of dexamethasone oral tablets crushed and placed in apple sauce or pudding in comparison with the IV solution mixed with sugar syrup and given orally. It is hypothesized that dexamethasone tablets crushed and administered in apple sauce or pudding will be more palatable and acceptable for pediatric patients receiving dexamethasone for an acute asthma exacerbation or croup.

Detailed description:

Arms: arm 1: Dexamethasone IV for PO solution mixed with sugar syrup to be given orally arm 2: Dexamethasone tablet crushed and placed in apple sauce or pudding to be given orally
Interventions: intervention 1: Dexamethasone IV for PO intervention 2: Dexamethasone crushed tablets
Intervention descriptions: intervention 1: Common pediatric emergency department practice intervention 2: Alternative route of administration for patients unable to swallow tablet whole

Protocol documents:
Prot_SAP_000.pdf: 
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Principal Investigator: Donald H. Arnold, MD, MPH                                             Version Date: 09 19 18 
Study Title: Randomized controlled trial of dexamethasone oral preparations to assess palatability and adverse effects in children with 
asthma and croup 
Institution/Hospital: Vanderbilt Children’s Hospital 
NCT03705273
Randomized controlled trial of dexamethasone 
oral preparations to assess palatability and adverse effects 
in children with asthma and croup
Protocol Date: 09.19.2018
Study Description and Protocol 
Principal Investigator: 
Donald H. Arnold, MD, MPH 
Pediatric Emergency Medicine 
Co-investigators 
Andrea Goettel, Pharm.D. 
Pediatric Pharmacy Resident 
Alison G. Grisso, Pharm.D., BCPPS 
Pediatric Clinical Pharmacist 
Matthew Schmidt, Pharm.D., BCPS, BCPPS 
Pediatric Clinical Pharmacist 
Vanderbilt Children’s Hospital 
2200 Children’s Way
Nashville, TN   37232-9100 
09.19.18 


Principal Investigator: Donald H. Arnold, MD, MPH                                             Version Date: 09 19 18 
Study Title: Randomized controlled trial of dexamethasone oral preparations to assess palatability and adverse effects in children 
with asthma and croup 
Institution/Hospital: Vanderbilt Children’s Hospital 
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I.
Specific Aim and Study Hypothesis
Specific Aim:  To examine the palatability and acceptability of oral dexamethasone tablets
crushed in apple sauce or pudding in comparison with the IV solution mixed with sugar syrup.
Hypothesis:  We hypothesize that dexamethasone tablets crushed and administered in apple
sauce or pudding at a dose of 0.6 mg/kg will be more palatable and acceptable in comparison to
the IV form of the drug mixed in sugar syrup, for acute asthma exacerbations or croup in children
aged 1 – 7 years in a pediatric emergency department.
II.
Summary of Approach
To address the Specific Aim we will conduct a 2-arm RCT of dexamethasone tablets crushed in
apple sauce or pudding in comparison to the current approach in the VCH ED, dexamethasone IV 
solution mixed in sugar syrup. The outcome, palatability and acceptability, will be assessed using a 
smiley-face analog scale and questionnaire that will be completed by the participant’s parent 1-hour after 
administration of dexamethasone.  
Treatment allocation (randomization) will be determined by a pre-determined randomization 
sequence in randomly-permuted blocks of 4, to be generated using Stata statistical software. Envelopes 
containing treatment allocation by sequential participant ID will be in the VCH-ED charting room where 
physicians and nurse practitioners enter orders for this medication in Epic. When a parent and patient 
provide consent/assent, the next envelope will be opened to determine treatment allocation. The clinician 
will then enter the order for dexamethasone tablets or IV solution in accordance with this. The clinician 
will ask the participant’s parent to complete the data collection form (enclosed with this application) 1-
hour after medication administration.   
Treatment allocation cannot be blinded because the vehicle (apple sauce, pudding or sugar syrup) 
may be associated with palatability and acceptability.  
III.
Background
Asthma is the most prevalent chronic serious disease of childhood and the most frequent reason for 
childhood hospitalization in the United States. Asthma and croup are common patient diagnoses in the 
pediatric emergency department, and national guidelines recommend oral dexamethasone (a 
corticosteroid) as a fundamental treatment for both conditions. Dexamethasone is the preferred 
corticosteroid because the duration of clinical effect is 2-3 days, a period sufficient to treat these 
conditions. The current dexamethasone preparation used at VCH is the intravenous (IV) preparation 
mixed with cherry syrup. Our nursing staff prefers this preparation. However, some children spit this 
preparation out or have vomiting afterward. 
IV.
Inclusion and Exclusion Criteria
a.
Inclusion criteria
i.
Diagnosis of acute asthma exacerbation or croup (laryngotracheitis) in the VCH
ED
ii.
Age 1 to 7 years
iii.
Dexamethasone treatment indicated
iv.
No other acute or chronic process accounting for signs and symptoms (e.g.,
foreign body aspiration, pneumonia, cystic fibrosis)
v.
Have not received systemic corticosteroid for current episode prior to enrollment
b.
Exclusion criteria
i.
Allergy to dexamethasone or apple sauce and pudding
ii.
Unable to take medication orally


Principal Investigator: Donald H. Arnold, MD, MPH                                             Version Date: 09 19 18 
Study Title: Randomized controlled trial of dexamethasone oral preparations to assess palatability and adverse effects in children 
with asthma and croup 
Institution/Hospital: Vanderbilt Children’s Hospital 
 
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V. 
Subject Recruitment and Enrollment 
We will enroll a convenience sample of 220 children 1-7 years of age and their parent, who will 
provide secondary data on their child. The investigators will be clinicians (attending physicians, fellows, 
pharmacists, nurses, or nurse practitioners) caring for patients in the VCH ED and will identify patients 
presenting with signs (e.g., tachypnea, wheezing, accessory muscle use) and symptoms (e.g., respiratory 
distress, dyspnea, cough,) consistent with an asthma exacerbation or croup (barky cough, inspiratory 
stridor).  
The investigator will seek written informed consent from the parent and verbal assent from the 
child. If these are provided, the patient will be enrolled as a participant. Based on the proposed sample 
size described in a later section of the protocol, we anticipate enrollment of 220 patients and 220 parents. 
 
VI. 
Study Procedures 
Study Design 
The study design will be an RCT with randomization in randomly-permuted blocks of four. After 
participant enrollment and ascertainment of treatment allocation (randomization), the clinician will order 
dexamethasone accordingly in tablet or IV form. The investigator will provide the parent with the study 
data form and instruct the parent in completion of this form 1-hour after dexamethasone administration.   
 
VII. 
Predictor Variables 
The predictor variable will be treatment-allocation (dexamethasone tablet or IV preparation 
administered orally.  
VIII. 
Outcome Variables 
The outcome variable will be palatability as defined by a 5-point “smiley-face” visual analog scale 
that the parent will complete on the study data form. Secondary outcomes will include emesis; need to re-
administer the medication, need to provide alternate vehicle for medication (e.g., intravenous or 
intramuscular).  
IX. 
Ethical Considerations 
Systemic corticosteroid is a fundamental component of treatment for acute asthma exacerbations 
and croup, and dexamethasone has been identified at VCH and nationally as the optimal systemic 
corticosteroid for these children. The IV form of dexamethasone is used currently at VCH and in most 
pediatric ED’s nationally. However, previous research has demonstrated that dexamethasone tablets are 
better tolerated than prednisolone (a different corticosteroid) syrup. There is equipoise whether 
dexamethasone as the IV form or tablet is more palatable and acceptable to these children, and this research 
seeks to answer the important question whether we should be using the tablets.  
X. 
Risks of Study Participation 
The risk to participants is not increased over current practice pertaining to administration of 
dexamethasone orally. The IV form is currently in use, and the tablets are widely acknowledged to be well 
tolerated by children. However, any apparent adverse events (e.g., allergy to apple sauce or pudding) will 
be reported by the investigators to Dr. Arnold who will immediately inform the IRB as noted below.  
XI. 
Reporting of Adverse Events or Unanticipated Problems involving Risk to Subjects or 
Others 
Any unexpected problems involving risks to subjects or others will be immediately reported to the 
Institutional Review Board of Vanderbilt University within ten days using the IRB form #1105.  


Principal Investigator: Donald H. Arnold, MD, MPH                                             Version Date: 09 19 18 
Study Title: Randomized controlled trial of dexamethasone oral preparations to assess palatability and adverse effects in children 
with asthma and croup 
Institution/Hospital: Vanderbilt Children’s Hospital 
 
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XII. 
Study Withdrawal or Discontinuation 
We are taking several measures to ensure that there is a clear distinction for the patient and 
parent/guardian(s) between clinical care and the research data collection for this investigation. Patients and 
their parent/guardian(s) will be told very explicitly by the investigators that their participation in this 
research investigation is entirely voluntary and that they may withdraw at any time. We will further 
emphasize verbally and in the informed consent document that a decision on the part of the patient or 
parent/guardian(s) to not participate will in no way change, compromise or jeopardize the patient’s care. 
Indeed, we anticipate that some eligible patients will not be enrolled on this basis.  
XIII. 
Data Management 
A Subject Data Form will be used for data acquisition. All data will be entered in a secure REDCap 
database. This data will then be entered into Stata® (v.8, College Station, TX) for statistical analysis. 
XIV. 
Clinicaltrials.gov registration:  Pending 
 
XV. 
Statistical Considerations 
We will examine palatability using the 5-point analog (“smiley-face”) scale and will ask the parent 
to make a mark on this scale. This mark will be used to estimate palatability as a continuous variable (e.g., 
5.6 cm).  
XVI. 
Sample Size 
In a cohort of children aged 2 – 10 years who received oral dexamethasone as the elixir and using 
a 5-point Hedonic scale (“smiley-face” scale) was used to assess palatability,1 Aljebab and colleagues 
reported a mean value for palatability of 3 with SD 1.1. If the true, mean difference between dexamethasone 
tablet and IV solution administered orally is 0.5, we will need to study 103 experimental subjects and 103 
control subjects to be able to reject the null hypothesis that the population means of the experimental and 
control groups are equal with probability (power) 0.9.   The Type I error probability associated with this 
test of this null hypothesis is 0.05. 
With the above in mind, we propose to enroll 110 participants in each treatment-allocation arm of 
this RCT to account for dropouts and missing data. 
 
XVII. 
Privacy and Confidentiality Issues 
After the parents have signed the consent, one copy will be given to the parents and one copy will 
be kept by Dr. Arnold in his office. All efforts, within reason, will be made to keep protected health 
information (PHI) private. PHI is health information that is or has been gathered or kept by Vanderbilt as a 
result of a subject’s healthcare.  This includes data gathered for research studies and can be traced back to 
the subject.  Using or sharing (“disclosure”) such data must follow federal privacy rules. By signing the 
consent for this study, subjects are agreeing (“authorization”) to the uses and likely sharing of PHI.  If a 
patient decides to be in this research study, he/she is also agreeing to let the study team use and share PHI 
as described below.  
As part of the study, Dr. Arnold and his study team may share the results of a subjects’ study and/or 
non-study linked lab tests, as well as parts of the medical record, to the groups named below. These groups 
may include people from the Federal Government Office for Human Research Protections, the Vanderbilt 
University Institutional Review Board.  Federal privacy rules may not apply to these groups; they have their 
own rules and codes to assure that all efforts, within reason, will be made to keep PHI private. Dr. Arnold 
may give health data, without a subject’s name, to others or use it for other research projects. Vanderbilt 
and Dr. Arnold and his staff will keep each subject’s PHI in strict confidence, and will comply with any 
and all laws regarding the privacy of such information. 


Principal Investigator: Donald H. Arnold, MD, MPH                                             Version Date: 09 19 18 
Study Title: Randomized controlled trial of dexamethasone oral preparations to assess palatability and adverse effects in children 
with asthma and croup 
Institution/Hospital: Vanderbilt Children’s Hospital 
 
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The study results will be kept in the subject’s research record for at least six years after the study 
is finished.  At that time, the research data that has not been put in the subject’s medical record will be 
destroyed. Any research data that has been put into the medical record will be kept for an unknown length 
of time. 
XVIII. 
Follow-up and Record Retention 
The study results will be kept in the subject’s research record for at least six years after the study 
is finished.  At that time, the research data that has not been put in the subject’s medical record will be 
destroyed. Any research data that has been put into the medical record will be kept for an unknown length 
of time. 
XIX. 
Data Safety and Monitoring Plan 
Surveillance for medical risks, including but not limited to exacerbation of airway obstruction and 
respiratory distress, will be performed continuously during the study of each subject by the study 
investigators. The clinical care team also monitors continuously for exacerbation of airway obstruction and 
is prepared to intervene immediately.  
The Principal Investigator (Dr. Arnold) will closely oversee the protocol to monitor for any adverse 
events.  Any adverse events will be reported as per IRB guidelines as noted above.  Electronic data have 
several levels of protection.  Any file that may contain patient identifiers will be password protected.  All 
computers upon which data are stored are likewise password protected and are running anti-virus programs 
that automatically update definitions.  All data are automatically backed-up to a secondary hard drive on a 
nightly basis.  Access to the Vanderbilt computer network is protected at the level of firewalls, TCP 
wrappers and university assigned user ID’s.  Data are secured with encryption algorithms and the network 
is maintained by the Medical Center’s Network Computer Services.  
 
REFERENCES 
1. 
Aljebab F, Alanazi M, Choonara I, Conroy S. Observational study on the palatability and 
tolerability of oral prednisolone and oral dexamethasone in children in Saudi Arabia and the UK. Arch 
Dis Child. 2018;103(1):83-8. Epub 2017/07/25. doi: 10.1136/archdischild-2017-312697. PubMed PMID: 
28735259; PMCID: PMC5754874.