Initiation of Acid Suppression Therapy Prospective Outcomes for Laryngomalacia
Phase: PHASE1
Conditions: Laryngomalacia, Gastro Esophageal Reflux
Sponsor: Reema Padia

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Study Protocol  
 
 
 
 
 
 
Official Title: Initiation of Acid Suppression Therapy Prospective 
Outcomes for Laryngomalacia 
  
 
 
ClinicalTrials.gov ID (NCT number): NCT04614974 
 
 
 
Protocol Date: 05/14/2021 
 
 
 
 

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Scientific Background 
 
Laryngomalacia (LM) is the most common cause of stridor in infants. Symptoms of 
gastroesophageal reflux (GER) are often seen in the setting of LM; therefore, acid suppression 
therapy (AST) has been empirically used in the management of this disorder. Our team recently 
performed a retrospective chart review assessing improvement of airway and dysphagia 
symptoms, weight gain, and need for surgery with AST. We have found that there was a similar 
improvement between LM severity groups and the majority of patients received AST. It is 
unclear if these improvements are due to AST or natural resolution of the disease. With 
heightened concerns of side effects related to AST in infants, particularly among those born 
prematurely, judicious use of these medications is needed. We are now performing a prospective 
study looking at the outcome differences in patients with laryngomalacia who are evaluated by 
speech language therapy (SLP) alone versus those with SLP evaluation and AST. There is no 
gold standard in treating mild and moderate LM patients and therefore this study would help 
establish these guidelines. 
 
Study Objectives 
 
Purpose: To determine the outcome differences in patients 6 months and younger with 
laryngomalacia and dysphagia who are evaluated by speech language therapy (SLP) alone versus 
those with both SLP evaluation and acid suppression therapy (AST) 
 
Hypothesis: We hypothesize that there will be no differences in outcomes between those that had 
SLP alone versus those that had both SLP and AST. 
 
Study Design & Methods 
 
Design: Prospective clinical trial with survey 
 
Methods: 
 
All Department of Pediatric Otolaryngology Airway clinic patients with a referral diagnosis of 
laryngomalacia will have their medical records screened for eligibility. All eligible families with 
infants that qualify for the study will be approached the day of clinic by their licensed physician 
to discuss the study. They will be given the Pittsburgh Airway Symptom Score (PASS) 
questionnaire and the Infant Gastroesophageal Reflux Questionnaire (I-GERQ-R) at the 
beginning of the appointment. The physician will then perform the standard procedures at the 
clinic appointment. The Flexible Laryngoscopy Findings sheet will be filled out in conjunction 
with the clinic procedures for objective data. The surveys will then be scored to determine true 
GERD (score >=16) and severe laryngomalacia (LM) (RED questions on the PASS), which 
would further exclude these patients. There are 12 total questions on the I-GERQ-R. On the 
PASS, questions 1 & 2 are in the GREEN category and signifies mild LM, YELLOW signifies 
moderate LM, and RED is severe LM. On the PASS questionnaire, "Yes" to either #1 or #2 and 

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nothing else is mild LM, "yes" to at least one #3-5 and none of #6-10 is moderate LM, and "yes" 
to any of the #6-10" indicates severe LM. There are 10 total questions on the PASS. 
Mild and moderate LM patients will be block randomized the day before the appointment to 
receive speech language therapy alone or speech language therapy with famotidine (Pepcid). 
Both treatments are standard of care in these patients as well as watchful observation. Speech 
language therapy is part of the normal clinic visit for LM patients. There is no gold standard of 
care for LM, therefore this trial is important to establish this. Patients will be randomized in both 
mild and moderate LM blocks before the appointment, as providers are unaware of the severity 
until the time of the appointment. After the appointment, if the family does not want to 
participate, the name will be taken off the randomization sheet completely or off the unused 
block. 
 
These patients will then be re-evaluated at their follow up appointment in 1 to 4 months. The 
families will take the PASS and I-GERQ-R surveys again to determine LM severity. If Pepcid is 
discontinued due to intolerance of side effects, they will be kept in the study in the same arm. If 
the family opts out of the follow-up appointment or they do not need to follow-up in-person, 
families will take the post surveys via REDCap or by mail. A REDCap link will be sent along 
with a letter to the caregivers to the caregivers' email address on file. If the families do not fill 
out the surveys within 2 weeks, paper copies of the surveys along with a letter to the caregivers 
will be sent to the caregivers' home address on file. If the families do not return the paper copy or 
the electronic copy of the surveys, researchers will call the participants for a reminder and will 
ask if the family wants another paper copy or survey link. The family may also answer the 
survey questions over the phone. 
 
Eligibility Criteria  
 
Inclusion:  
 Pediatric patients ages 0 to 6 months who do need meet the criteria at the initial 
appointment for supraglottoplasty 
 Seen in UPMC CHP Otolaryngology Department 
 Laryngomalacia without prolonged (>20 seconds) cyanosis, apnea, nor failure to thrive. 
 
Exclusion: 
 Children over the age of 6 months old will be excluded from participation. 
 Premature infants (<37 weeks gestation) 
 Patients with lung disease. 
 Laryngomalacia with cyanosis, apnea, and failure to thrive 
 Sleep induced laryngomalacia 
 Patients with craniofacial abnormalities 
 Patients with a syndrome 
 Patients with additional airway abnormalities, seen before or at consult 
 Patients with symptoms that necessitate surgery 
 Patients with prior cardiac surgery 
 Patients with AST prescribed prior to the initial ENT consult. 
 

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Statistical Analysis Plan 
 
 
 
 
 
 
Official Title: Initiation of Acid Suppression Therapy Prospective 
Outcomes for Laryngomalacia 
  
 
 
ClinicalTrials.gov ID (NCT number): NCT04614974 
 
 
 
Protocol Date: 05/14/2021 
 
 

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Study Objectives 
 
Aim: To determine the outcome differences in patients 6 months and younger with 
laryngomalacia and dysphagia who are evaluated by speech language therapy (SLP) alone versus 
those with both SLP evaluation and acid suppression therapy (AST) 
 
Study Outcomes 
 
Primary Outcome 
 Airway Symptom Score Change From Consult (Baseline) to 3 Month Follow-up 
Appointment.  
o This will be parent-reported and measured using the Pittsburgh Airway Symptom 
Score (PASS) questionnaire. The PASS is a scale from 0-10 with a higher score 
indicating a worse outcome. This outcome will be assessed at the consult and the 
3 month follow-up appointment. 
 Infant Gastroesophageal Reflux Questionnaire (I-GERQ-R) Score Change From Consult 
(Baseline) to 3 Month Follow-up Appointment.  
o This will be parent-reported. There are 12 questions on the surveys on a scale of 
0-42. A higher score indicates a worse outcome. Those with a score of >=16 on 
this survey at the initial consult are excluded from the study, indicating true 
gastroesophageal reflux disease (GERD). This outcome will be assessed at the 
consult and the 3 month follow-up appointment. 
 Change in Incidence of Airway Symptoms From Consult up to 1 Year Assessed Via 
Electronic Medical Chart Review.  
o Change in incidence of airway symptoms from consult up to 1 year assessed via 
electronic medical chart review. Notes from the Department of Otolaryngology 
will be reviewed which include reported symptoms from caregivers and 
symptoms seen upon exam. Airway symptoms included periods of apnea, chest 
wall retractions, cyanosis, stridor, noisy breathing, and increased respiratory rate. 
 Change in Incidence of Dysphagia Symptoms From Consult up to 1 Year Assessed Via 
Electronic Medical Chart.  
o Change in incidence of dysphagia symptoms from consult up to 1 year assessed 
via electronic medical chart review. Notes from the Department of 
Otolaryngology will be reviewed which include reported symptoms from 
caregivers and symptoms seen upon exam. Dysphagia symptoms included 
choking, coughing, gagging with feeds and/or emesis after feeds. 
 
Secondary Outcomes 
 Weight (kg) From Consult up to 1 Year.  
o Weight change in kilograms assessed from medical chart review from consult up 
to 1 year 
 Number of Participants With the Need for Supraglottoplasty Surgery (Escalation of 
Treatment) up to 1 Year.  
o The need for escalation of treatment with supraglottoplasty surgery will be 
assessed through medical chart review up to 1 year. 

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 Number of Participants With the Need for Acid Suppression Therapy Medication 
(Famotidine) From Speech Language Therapy Alone Group From the Day After the 
Consult up to the 3 Month Follow up Appointment.  
o The speech language therapy alone group will be assessed for the need for a 
prescription for acid suppression therapy (famotidine) from the day after the 
consult up to 1 year. 
 Number of Participants With Each Type of Laryngomalacia (Types 1-3) Found on the 
Flexible Laryngoscopy Procedure at the Consult.  
o All patients will be scoped with a flexible laryngoscopy at the initial consult and 
the type of laryngomalacia (Types 1-3) will be noted. 
 Number of Participants With the Need for a Different Acid Suppression Therapy 
Medication (Other Than Famotidine) From the Day After the Consult up to the 3 Month 
Follow up Appointment.  
o Both groups will be assessed for the need for a different acid suppression therapy 
medication (other than famotidine) from the day after the consult up to the 3 
month follow up appointment. 
 
Sample Size Calculation 
 
Based on data from Dang et al [1], 62 participants per group will be needed to address the 
hypothesis that there is no difference in airway symptom improvement between AST and no-
AST groups with alpha=.05 and power=.80 (two-tailed Fisher's exact test, G*Power 3.1). Target 
enrollment will be 160 participants (80 in the AST group and 80 in the no-AST group, with 40 
with mild laryngomalacia and 40 with moderate laryngomalacia in each group) to account for 
attrition. 
 
[1] Dang S, McCoy JL, Shaffer AD, Tobey ABJ, Dohar JE, Simons JP, Maguire RC, Padia R. 
Initiation of acid suppression therapy for laryngomalacia. Am J Otolaryngol. 2022;43(3):103434. 
doi:10.1016/j.amjoto.2022.103434 
 
 
 

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Analyses 
 
Stata/SE 16.1 will be used for all statistical analysis.  
P value < .05 will be used for statistical significance.  
 
Baseline characteristics will be compared between AST and no-AST groups using Chi-squared 
or Fisher’s exact test for categorical data and t-test (normally distributed) or Wilcoxon rank-sum 
(not normally distributed) for continuous data. Primary outcome measures will be change in 
LASS and I-GERQ-R scores from initial visit to follow-up and change in airway and dysphagia 
symptoms assessed by chart review during the 1 year following the initial visit. The LASS and I-
GERQ-R scores will be compared between initial and follow-up surveys using Wilcoxon signed-
rank tests. Change scores (post-pre) will be calculated for LASS and I-GERQ-R, and differences 
in the improvement in scores based on laryngomalacia severity or randomization group will be 
evaluated using Wilcoxon rank-sum tests. Associations between LASS or I-GERQ-R and time 
between initial and follow-up surveys will be evaluated using Spearman rank correlation. 
Symptoms and weight at initial and follow-up visits will be compared using McNemar’s and 
Wilcoxon signed-rank tests, respectively. Change in weight percentile based on laryngomalacia 
severity or randomization group will be evaluated using Wilcoxon rank-sum tests. 
 
Cross-Over 
Intent-to-treat analysis will be performed. 
 
Analysis Inclusion  
Only those who meet eligibility criteria will be included in the final analysis. Specific outcome 
measures will be ascertained only in patients who complete follow-up questionnaires, as 
indicated.  
 
Missing Data 
Data imputation will not be used for missing data.  
 
Harms 
 
Serious adverse events and non-serious adverse events resulting in emergency department visits 
will be collected up until 1 year following the initial consult appointment.