Clinical trial NCT02707523: Prospective Pilot Clinical Trial of Azithromycin Treatment In Respiratory Syncytial Virus (RSV)- Induced Respiratory Failure In Children
Official title: Prospective Pilot Clinical Trial of Azithromycin Treatment In RSV-induced Respiratory Failure In Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Respiratory Syncytial Virus
Keywords: RSV
respiratory support
ICU
Azithromycin
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2016-03-14
Enrollment: 48
Sex: ALL
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
timeFrame: Baseline through Day 3
measure: Nasal Total Matrix Metalloproteinase (MMP)-9 Level
timeFrame: Day 3
measure: Pharmacokinetic-Plasma Half Life of AZM
timeFrame: From baseline to 72 hours post treatment
measure: Pharmacokinetic-Lung Half Life of AZM
timeFrame: From baseline to 72 hours post treatment
Secondary outcomes:
measure: Duration of Mechanical Ventilation in Days
timeFrame: Pre-treatment through 2 weeks
measure: Duration of BiPAP in Days
timeFrame: Pre-treatment through 2 weeks
measure: Duration of High Flow Nasal Cannula in Days
timeFrame: Pre-treatment through 2 weeks
measure: Duration of Oxygenation in Days
timeFrame: Pre-treatment through 2 weeks
measure: Duration of Hospitalization in Days
timeFrame: Pre-treatment through 2 weeks
measure: Duration of PICU Stay in Days
timeFrame: Pre-treatment through 2 weeks
Other outcomes:
measure: Lung Matrix Metalloproteinase (MMP) Level
timeFrame: Day 3
Locations:
city: Birmingham
country: United States
facility: UAB
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Michele Kong, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kong M, Zhang WW, Sewell K, Gorman G, Kuo HC, Aban I, Ambalavanan N, Whitley RJ. Azithromycin Treatment vs Placebo in Children With Respiratory Syncytial Virus-Induced Respiratory Failure: A Phase 2 Randomized Clinical Trial. JAMA Netw Open. 2020 Apr 1;3(4):e203482. doi: 10.1001/jamanetworkopen.2020.3482.