Azithromycin Treatment for Respiratory Syncytial Virus-induced Respiratory Failure in Children

Study Overview
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Brief Summary
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The overarching hypothesis of the ARRC trial is that administration of Azithromycin (AZM) during acute, Respiratory Syncytial Virus (RSV)-induced respiratory failure will be beneficial, mediated through the matrix metalloproteinase (MMP)-9 pathway.

Detailed Description
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The proposed study will be a randomized, double-blinded, placebo-controlled Phase III trial to examine the efficacy of AZM therapy relative to placebo in reducing RSV-related morbidity. Patients will be recruited during acute hospitalization and admission to the ICU at 7 pediatric hospitals. The target population selected is pediatric patients with severe RSV lung disease as defined by need for ICU management and intensive respiratory support.

Official Title
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Azithromycin Treatment for Respiratory Syncytial Virus-induced Respiratory Failure in Children

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Drug: AZM Group
* Other: Control Group


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Admission to the pediatric ICU with a confirmed diagnosis of RSV infection. RSV infection is based on a positive nasal swab for RSV fluorescent antibody or via multiplex assay or culture; Requiring intensive respiratory support defined as either mechanical ventilation or NIV (BiPAP or CPAP) or HFNC (at >1 L/kg/min of flow Enrollment into the study within 48 hours of ICU admission and placement on intensive respiratory support; Onset of RSV-related symptoms must be less than 5 days Age: Neonates-2 years. For those less than 1 week of age, they must have been discharged home from the hospital after their birth. Exclusion criteria: AZM use within 7 days of ICU admission; Contraindication to AZM use including known hypersensitivity to AZM, erythromycin, any macrolide, or ketolide drug, patients with significant hepatic impairment (direct bilirubin >1.5 mg/dL or ALT ≥ 10 times the upper limits of normal); Patients with known cardiac disease, cardiac arrhythmia or with electrocardiogram QT interval corrected for heart rate (QTc) ≥ 450 milisecond (ms); Intensive respiratory support greater than 48 hours prior to ICU admission; Chronic ventilation or supplemental oxygen need at home; Immunosuppressive conditions such as those post heart or hematopoietic stem cell transplant or receiving chemotherapy and chronic steroids; History of pyloric stenosis; AZM is deemed necessary for clinical treatment (for instance, if patient has pertussis).

Ages Eligible for Study
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Minimum Age: 3 Days
Maximum Age: 2 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control Group<br> | Other: Control Group<br>* Saline will be given intravenous daily for 3 days once patients are consented and enrolled into the study.<br>|
| Active Comparator: AZM 20mg/kg Treatment Group<br> | Drug: AZM Group<br>* AZM at 20 mg/kg will be given intravenous daily for 3 days once patients are consented and enrolled into the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of Hospitalization | Duration of hospitalization in days for enrolled subjects | At discharge (Approximately 2 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of oxygenation | Duration of oxygenation in days for enrolled subject | At discharge (Approximately 1 week) | 
| Length of ICU stay | Duration of ICU stay in days for enrolled subjects | At ICU discharge (Approximately 1 week) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RSV, AZM, ICU, Respiratory Support, Children