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

Phase 2

Completed

• Conditions: Respiratory Syncytial Virus
• Interventions: Drug: Placebo; Drug: Azithromycin 10 mg; Drug: Azithromycin 20mg

• Registration Number: NCT02707523
• Lead Sponsor: University of Alabama at Birmingham

Brief Summary

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2016-01-01
• Study First Submitted: 2016-02-20
• Study First Submitted QC: 2016-03-11
• Study First Posted: 2016-03-14
• Primary Completion: 2019-02-06
• Disposition First Submitted: 2020-04-23
• Disposition First Submitted QC: 2020-04-23
• Disposition First Posted: 2020-04-28
• Results First Submitted: 2020-05-08
• Results First Submitted QC: 2020-05-08
• Results First Posted: 2020-05-27
• Study Completion: 2020-06-20
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-07
• Last Update Posted: 2020-07-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Control	Placebo	Placebo controlled (normal saline) daily for 3 days
Azithromycin (10 mg/kg)	Azithromycin 10 mg	10 mg/kg IV Azithromycin daily for 3 days
Azithromycin (20 mg/kg)	Azithromycin 20mg	20 mg/kg IV Azithromycin daily for 3 days

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic-Lung Half Life of AZM	From baseline to 72 hours post treatment	Measurement of AZM half life in the lung
Nasal Total Matrix Metalloproteinase (MMP)-9 Level	Day 3	To determine the concentration of total MMP-9 levels in the nasal compartment
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	Baseline through Day 3	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
Pharmacokinetic-Plasma Half Life of AZM	From baseline to 72 hours post treatment	Measurement of AZM half life in the plasma

Secondary Outcome Measures

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

Trial Locations

Locations (1)

UAB; 🇺🇸 Birmingham, Alabama, United States