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

NCT ID: NCT02700087

Last Updated: 2017-11-17

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2017-02-28

Brief Summary

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.

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.

Conditions

Laryngomalacia; Acid Reflux; Stridor

Keywords

Laryngomalacia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

ranitidine or famotidine

Intervention Type: DRUG

Patients with symptomatic laryngomalacia will receive ranitidine, famotidine, or placebo medications in order to see if these medications help their symptoms to resolve.

Placebo

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

ranitidine or famotidine

Intervention Type: DRUG

Patients with symptomatic laryngomalacia will receive ranitidine, famotidine, or placebo medications in order to see if these medications help their symptoms to resolve.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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)

• Maximum Eligible Age: 4 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Douglas Sidell

Assistant Professor - Med Center Line, Otolaryngology- Head and Neck Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Douglas R Sidell, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Lucile Packard Children's Hospital Stanford

Palo Alto, California, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 17513991 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10569405 (View on PubMed)

Study Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

IRB-35551

Identifier Type: -

Identifier Source: org_study_id