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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Respiratory Syncytial Virus

Intervention / Treatment
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* Drug: Azithromycin 10 mg
* Drug: Azithromycin 20mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RSV, respiratory support, ICU, Azithromycin