Prospective Pilot Clinical Trial of Azithromycin Treatment In Respiratory Syncytial Virus (RSV)- Induced Respiratory Failure In Children

Prospective Pilot Clinical Trial of Azithromycin Treatment In RSV-induced Respiratory Failure In Children

This randomized, double-blind, placebo-controlled phase 2 trial will be conducted at a single tertiary pediatric intensive care unit (PICU). The study will include children with RSV infection who were admitted to the pediatric intensive care unit and require respiratory support via positive pressure ventilation (invasive and noninvasive).

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus
• Intervention / Treatment: Drug: Placebo; Drug: Azithromycin 10 mg; Drug: Azithromycin 20mg

Detailed Description

Eligible participants include all children admitted to the PICU at Children's of Alabama with a diagnosis of RSV infection and requiring positive pressure ventilation, invasive or noninvasive, including bilevel positive airway pressure (BiPAP) or high flow nasal cannula (HFNC) oxygen (ie, >1 L/kg/min of flow, with 5 L/min flow for children weighing <5 kg). During hospitalization, all patients will be treated according to the American Academy of Pediatrics guidelines for the management of bronchiolitis, primarily supportive care. Participants will then be randomized according to a permuted-block design to receive either placebo (saline) or AZM (Fresenius Kabi) at 10mg/kg/d (ie, standard dose) or 20mg/kg/d (ie, high dose) intravenously every 24 hours for 3 days. All biologic samples collected will be analyzed in the PI's lab at the University of Alabama at Birmingham. Drug pharmacokinetics will be performed at the Pharmaceutical Sciences Research Institute of Samford University, Birmingham, AL.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • UAB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Admission to the PICU with RSV infection
• Need for positive pressure ventilation (invasive and non-invasive)
• Randomization and drug/placebo initiation within 48 hours of admission to Pediatric Intensive Care Unit

Exclusion Criteria:

• Azithromycin use within 7 days of PICU admission

• Contraindication to azithromycin use including:

  • Patients with electrocardiogram QT interval corrected for heart rate (Qtc) ≥ 450 ms
  • Patients with significant hepatic impairment (direct bilirubin >1.5 mg/dL)
  • Known hypersensitivity to azithromycin, erythromycin, any macrolide, or ketolide drug
  • Cardiac arrhythmia
• History of pyloric stenosis
• Immunocompromised children (any cause)
• Current use of any medication known to cause QT prolongation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control; Placebo controlled (normal saline) daily for 3 days	Drug: Placebo
Active Comparator: Azithromycin (10 mg/kg); 10 mg/kg IV Azithromycin daily for 3 days	Drug: Azithromycin 10 mg; Other Names: Z-Pak; Zithromax
Active Comparator: Azithromycin (20 mg/kg); 20 mg/kg IV Azithromycin daily for 3 days	Drug: Azithromycin 20mg; Other Names: Z-Pak; Zithromax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	To determine the safety profile of AZM at 10 mg/kg and 20 mg/kg IV X 3 days in children with RSV-induced respiratory failure	Baseline through Day 3
Nasal Total Matrix Metalloproteinase (MMP)-9 Level	To determine the concentration of total MMP-9 levels in the nasal compartment	Day 3
Pharmacokinetic-Plasma Half Life of AZM	Measurement of AZM half life in the plasma	From baseline to 72 hours post treatment
Pharmacokinetic-Lung Half Life of AZM	Measurement of AZM half life in the lung	From baseline to 72 hours post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Mechanical Ventilation in Days	Duration of mechanical ventilation in days for enrolled subjects	Pre-treatment through 2 weeks
Duration of BiPAP in Days	Duration of BiPAP in days for enrolled subjects	Pre-treatment through 2 weeks
Duration of High Flow Nasal Cannula in Days	Duration of High Flow Nasal Cannula in days for enrolled subjects	Pre-treatment through 2 weeks
Duration of Oxygenation in Days	Duration of oxygenation in days for enrolled subjects	Pre-treatment through 2 weeks
Duration of Hospitalization in Days	Duration of hospitalization in days for enrolled subjects	Pre-treatment through 2 weeks
Duration of PICU Stay in Days	Duration of PICU stay in days for enrolled subjects	Pre-treatment through 2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung Matrix Metalloproteinase (MMP) Level	To determine the concentration of MMP-9 levels in the lung compartment	Day 3

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Michele Kong, MD, University of Alabama at Birmingham

Publications and helpful links

General Publications

• Kong M, Zhang WW, Sewell K, Gorman G, Kuo HC, Aban I, Ambalavanan N, Whitley RJ. Azithromycin Treatment vs Placebo in Children With Respiratory Syncytial Virus-Induced Respiratory Failure: A Phase 2 Randomized Clinical Trial. JAMA Netw Open. 2020 Apr 1;3(4):e203482. doi: 10.1001/jamanetworkopen.2020.3482.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): February 6, 2019
• Study Completion (Actual): June 20, 2020

Study Registration Dates

• First Submitted: February 20, 2016
• First Submitted That Met QC Criteria: March 11, 2016
• First Posted (Estimate): March 14, 2016

Study Record Updates

• Last Update Posted (Actual): July 22, 2020
• Last Update Submitted That Met QC Criteria: July 7, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: ICU; RSV; Azithromycin; respiratory support
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: FWA00005960 (Other Grant/Funding Number: DEPT. HEALTH AND HUMAN SERVICES)