In Infants With Laryngomalacia, Does Acid-Blocking Medication Improve Respiratory Symptoms?

In Infants With Symptoms of Tracheomalacia or Laryngomalacia, Does Acid-Blocking Medication Improve Respiratory Symptoms? A Randomized, Controlled Trial

All neonates, ages 0 to 4 months, presenting to LPCH pediatric ENT clinic for airway difficulties or stridor will be screened for inclusion. As is consistent with an acceptable standard of medical care, these children will undergo a flexible nasal endoscopic exam to make the diagnosis of laryngomalacia, as well as be weighed and a breastfeeding history taken. If laryngomalacia is present, the study staff with then administer the Infant Gastroesophageal Reflux Questionnaire (IGERQ) and an airway symptoms questionnaire (ASQ).

Those babies with an IGERQ score of less than sixteen (no more than mild reflux) and an ASQ score greater than six will be eligible for randomization. The patient will then be randomly placed in the control group (placebo) or the intervention group (ranitidine 2mg/kg every 12 hours or famotidine 0.5 mg/kg daily). Patients will stay on medication for a minimum of 6 months, or until symptoms resolve. Patients will be seen in follow up at 1, 2, 3, 4, 5, 6, 8 and 10 months. At which time I-GERQ, ASQ and weights will be taken. The primary outcome measure will be the time for the ASQ score to drop to normal on ranitidine or famotidine versus placebo.

A secondary outcome will be weight gain in percentile. If the patient's I-GERQ score goes above 16 at any time in the study, the patient will be crossed over to the treatment arm and started on medical treatment.

Study Overview

• Status: Withdrawn
• Conditions: Acid Reflux; Stridor; Laryngomalacia
• Intervention / Treatment: Drug: ranitidine or famotidine; Drug: Placebo

Detailed Description

Laryngomalacia, or a soft, floppy upper airway, is the most common cause of noisy breathing in neonates. It is caused by a combination of factors including neuromuscular weakness, cartilaginous inadequacy, and anatomic abnormalities in the voice box. The majority of affected babies' symptoms resolve by one year without intervention, but around 5% of cases require surgical intervention to treat failure to thrive or obstructive sleep apnea.

Many babies with laryngomalacia are treated empirically with H2 blockers such as ranitidine or famotidine to prevent reflux of stomach acid from causing further inflammation in an already compromised upper airway. However, to date no study has been performed to show a definitive benefit of these medications.

The investigators hope to determine whether H2 blockers such as ranitidine and famotidine improve airway symptoms in babies with laryngomalacia. This will have an effect on practice guideline for one of the most common problems encountered in pediatric otolaryngology.

All neonates, ages 0 to 4 months, presenting to LPCH pediatric ENT clinic for airway difficulties or stridor will be screened for inclusion. As is consistent with an acceptable standard of medical care, these children will undergo a flexible nasal endoscopic exam to make the diagnosis of laryngomalacia, as well as be weighed and a breastfeeding history taken. If laryngomalacia is present, the study staff with then administer the Infant Gastroesophageal Reflux Questionnaire (IGERQ) and an airway symptoms questionnaire (ASQ).

Those babies with an IGERQ score of less than sixteen (no more than mild reflux) and an ASQ score greater than six will be eligible for randomization. The patient will then be randomly placed in the control group (placebo) or the intervention group (ranitidine 2mg/kg every 12 hours or famotidine 0.5 mg/kg daily). Patients will stay on medication for a minimum of 6 months, or until symptoms resolve. Patients will be seen in follow up at 1, 2, 3, 4, 5, 6, 8 and 10 months. At which time I-GERQ, ASQ and weights will be taken. The primary outcome measure will be the time for the ASQ score to drop to normal on ranitidine or famotidine versus placebo.

A secondary outcome will be weight gain in percentile. If the patient's I-GERQ score goes above 16 at any time in the study, the patient will be crossed over to the treatment arm and started on medical treatment.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital Stanford

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 0 - 4 months old
• stridor and flexible laryngoscopy demonstrating laryngomalacia
• airway symptom score over 4
• only has physiologic GER (I-GERQ < 16)

Exclusion Criteria:

• requiring surgery for LGM
• other airway dz seen on flexible laryngoscopy
• history of or already on PPI therapy
• minimal/mild airway symptoms (airway score < 4)
• pathologic GERD (I-GERQ greater than 16) - These pts cannot be randomized because this is the standard score in Pediatric GI literature strongly indicating anti-reflux meds
• premature birth (< 36 weeks)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: H2 blocker versus placebo; The patient will then be randomly placed in the control group (placebo) or the intervention group (ranitidine 2mg/kg every 12 hours or famotidine 0.5 mg/kg daily). Patients will stay on medication for a minimum of 6 months, or until symptoms resolve. Patients will be seen in follow up at 1, 2, 3, 4, 5, 6, 8 and 10 months. At which time I-GERQ, ASQ and weights will be taken. The primary outcome measure will be the time for the ASQ score to drop to normal on ranitidine or famotidine versus placebo.	Drug: ranitidine or famotidine; Patients with symptomatic laryngomalacia will receive ranitidine, famotidine, or placebo medications in order to see if these medications help their symptoms to resolve.; Drug: Placebo; Patients with symptomatic laryngomalacia who meet inclusion criteria will be randomized to receive placebo, ranitidine or famotidine, in order to see if these medications help their symptoms to resolve.
Active Comparator: Treatment arm; Patients who develop severe airway symptoms while they are in the H2 blocker versus placebo arm will then cross over to the treatment arm of the study. These patients will exit randomization and be unblinded. These patients will all be given H2 blockers, and the effects of the H2 blockers will be monitored and studied. Alternatively, patients' families may also elect to undergo surgery to treat laryngomalacia.	Drug: ranitidine or famotidine; Patients with symptomatic laryngomalacia will receive ranitidine, famotidine, or placebo medications in order to see if these medications help their symptoms to resolve.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to normalization of airway symptoms score	The primary outcome measure will be the time for the ASQ score to drop to normal on ranitidine or famotidine versus placebo.	10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight gain	A secondary outcome will be weight gain in percentile.	10 month

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Douglas R Sidell, MD, Stanford University

Publications and helpful links

General Publications

• Thompson DM. Abnormal sensorimotor integrative function of the larynx in congenital laryngomalacia: a new theory of etiology. Laryngoscope. 2007 Jun;117(6 Pt 2 Suppl 114):1-33. doi: 10.1097/MLG.0b013e31804a5750.
• Olney DR, Greinwald JH Jr, Smith RJ, Bauman NM. Laryngomalacia and its treatment. Laryngoscope. 1999 Nov;109(11):1770-5. doi: 10.1097/00005537-199911000-00009.

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Anticipated): February 1, 2017
• Study Completion (Anticipated): February 1, 2017

Study Registration Dates

• First Submitted: February 23, 2016
• First Submitted That Met QC Criteria: March 4, 2016
• First Posted (Estimate): March 7, 2016

Study Record Updates

• Last Update Posted (Actual): November 17, 2017
• Last Update Submitted That Met QC Criteria: November 15, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Laryngomalacia
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Congenital Abnormalities; Musculoskeletal Diseases; Connective Tissue Diseases; Otorhinolaryngologic Diseases; Musculoskeletal Abnormalities; Laryngeal Diseases; Cartilage Diseases; Signs and Symptoms, Respiratory; Laryngomalacia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Anti-Ulcer Agents; Histamine Antagonists; Histamine Agents; Histamine H2 Antagonists; Famotidine; Ranitidine; Ranitidine bismuth citrate
• Other Study ID Numbers: IRB-35551

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Study Data/Documents

1. Informed Consent Form
   Information identifier: Consent form cycle 3