Overview
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.
Description
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.
Eligibility
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).