Azithromycin to Prevent Wheezing Following Severe RSV Bronchiolitis-II

NCT02911935 | Completed Phase 2 Results DMC

• 1 other identifier: 201603018
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of the APW-RSV II clinical trial is to evaluate if the addition of azithromycin to routine bronchiolitis care, among infants hospitalized with RSV bronchiolitis, reduces the occurrence of recurrent wheeze during the preschool years.

Conditions

Respiratory Syncytial Virus, Bronchiolitis

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Experienced the Occurrence of a Third Episode of Post-RSV Wheezing (Recurrent Wheeze)

  Episodes of wheezing were captured at each of the study telephone interviews and clinic visits using the question, "Has your child's chest sounded wheezy or whistling (with and without a cold)?". A new wheezing episode was defined if at least 7 days without wheezing had been reported since the previous episode.

  Follow up duration of 18-48 months

Secondary Outcomes (6)

• Number of Participants Who Had Physician Asthma Diagnosis

  Follow up duration of 18-48 months

• Annualized Number of Days With Respiratory Symptoms (Wheezing, Cough, or Shortness of Breath)

  Follow up duration of 18-48 months

• Annualized Number of Days With Albuterol Use

  Follow up duration of 18-48 months

• Annualized Number of Oral Corticosteroid Courses

  Follow up duration of 18-48 months

• Annualized Number of Antibiotic Courses

  Follow up duration of 18-48 months

Study Arms (2)

Oral azithromycin

ACTIVE COMPARATOR

Oral Azithromycin

Drug: Oral azithromycin

Placebo

PLACEBO COMPARATOR

Oral Placebo

Drug: Placebo

Interventions

Oral azithromycin DRUG

Oral azithromycin 10mg/kg/day for 7 days; then oral azithromycin 5mg/kg/day for 7 additional days

Also known as: Azithromycin suspension

Oral azithromycin

Placebo DRUG

Placebo suspension

Placebo

Eligibility Criteria

• Age: 1 Month - 18 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age: 1-18 months.
• Hospitalization for the first episode of RSV bronchiolitis.
• Confirmed RSV infection by positive nasal swab results (PCR assay and/or direct antigen detection).
• At least two of the following symptoms/signs of bronchiolitis: respiratory rate greater than 40 breaths/minute; cough; wheezing; audible rales, crackles, and/or rhonchi; paradoxical chest movements (retractions)28.
• Duration of respiratory symptoms from onset of symptoms of the current illness to admission is 120 hours (5 days) or less.
• Randomization can be performed within 168 hours (7 days) from onset of symptoms.
• Willingness to provide informed consent by the child's parent or guardian.

You may not qualify if:

• Prematurity (gestational age \< 36 weeks).
• Presence or history of other significant disease (CNS, lung, cardiac, renal, GI, hepatic disease, hematologic, endocrine or immune disease). Children with atopic dermatitis and/or food allergy will not be excluded from the study.
• Clinically significant gastroesophageal reflux currently treated with a daily anti-reflux medication (anti- H2 or PPI).
• The child has significant developmental delay/failure to thrive, defined as weight \< 3% for age and gender.
• History of previous (before the current episode) wheeze or previous (before the current episode) treatment with albuterol.
• History of previous treatment with corticosteroid (systemic or inhaled) for respiratory issues.
• Treatment (past or present) with montelukast.
• Participation in another clinical trial.
• Participant requires invasive mechanical ventilation due to RSV bronchiolitis.
• Evidence that the family may be unreliable or non-adherent, or has definitive plans to move from the clinical center area before trial completion.
• Contraindication of use of azithromycin or any other macrolide antibiotics such as history of allergic reaction (or other adverse reaction) to these antibiotics.
• Diagnosis of asthma.
• Treatment with other medication that may cause QT interval prolongation.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Department of Pediatrics, Washington University School of Medicine; and St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Related Publications (2)

• Beigelman A, Goss CW, Wang J, Srinivasan M, Boomer J, Zhou Y, Bram S, Casper TJ, Coverstone AM, Kanchongkittiphon W, Kuklinski C, Storch GA, Schechtman KB, Castro M, Bacharier LB. Azithromycin therapy in infants hospitalized for respiratory syncytial virus bronchiolitis: Airway matrix metalloproteinase-9 levels and subsequent recurrent wheeze. Ann Allergy Asthma Immunol. 2024 May;132(5):623-629. doi: 10.1016/j.anai.2024.01.001. Epub 2024 Jan 17.

  PMID: 38237675 DERIVED

• Beigelman A, Srinivasan M, Goss CW, Wang J, Zhou Y, True K, Ahrens E, Burgdorf D, Haslam MD, Boomer J, Bram S, Burnham CD, Casper TJ, Coverstone AM, Kanchongkittiphon W, Kuklinski C, Storch GA, Wallace MA, Yin-DeClue H, Castro M, Schechtman KB, Bacharier LB. Azithromycin to Prevent Recurrent Wheeze Following Severe Respiratory Syncytial Virus Bronchiolitis. NEJM Evid. 2022 Apr;1(4):10.1056/evidoa2100069. doi: 10.1056/evidoa2100069. Epub 2022 Feb 27.

  PMID: 37621674 DERIVED

MeSH Terms

Conditions

Bronchiolitis

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Limitations and Caveats

1. Our ultimate goal was to examine an asthma prevention strategy. However, the primary outcome was defined as recurrent wheeze during 2-4 years of follow-up. This was previously done in other studies in this field. 2. The study primary outcome measure was wheeze assessed by the parents, which has a relatively low correlation with wheeze assessed by physicians. However, a systematic bias is unlikely as both groups were evaluated by the same method

Results Point of Contact

• Title: Dr. Avraham Beigelman
• Organization: Washington University School of Medicine.

beigelmana@wustl.edu

314-454-2694

Study Officials

• Avraham Beigelman, MD, MSCI

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Study Record Dates

• First Submitted: September 18, 2016
• First Posted: September 22, 2016
• Study Start: November 1, 2016
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: June 7, 2022
• Results First Posted: June 7, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: A month after publication
• Access Criteria: See above

Locations

US (1)