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

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.

Detailed 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 10 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.

Interventions

• Drug AZM Group
  AZM at 20 mg/kg will be given intravenous daily for 3 days once patients are consented and enrolled into the study.
• Other Control Group
  Saline will be given intravenous daily for 3 days once patients are consented and enrolled into the study.

Primary outcome measures

• Length of Hospitalization [Time frame: At discharge (Approximately 2 weeks)]

Secondary outcome measures (2)

• Duration of oxygenation [Time frame: At discharge (Approximately 1 week)]
• Length of ICU stay [Time frame: At ICU discharge (Approximately 1 week)]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 15 centers

• The University of Alabama at Birmingham — Birmingham
• University of California San Francisco — San Francisco
• Yale School of Medicine — New Haven
• Children's National Hospital — Washington D.C.
• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago
• Riley Children's Health — Indianapolis
• St. Louis Children's Hospital — St Louis
• University of Nebraska Medical Center — Omaha
• … and 7 more centers

Identifiers

NCT: NCT05026749 · IRB-300007862 · 1R01HD105678-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗