Prospective Pilot Clinical Trial of Azithromycin Treatment In RSV-induced Respiratory Failure In Children
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Nasal Total Matrix Metalloproteinase (MMP)-9 Level
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participant, clinical providers and study staff are masked to the intervention. The random assignment of treatment was determined by random permutation. A statistician generated the randomization schedule and provided the randomization schedule (with randomization IDs) in an excel file to the study pharmacist in charge of dispensing the appropriate treatment.
入排标准
- 年龄范围
- — 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Control
Placebo controlled (normal saline) daily for 3 days
干预措施: Placebo (Drug)
Azithromycin (10 mg/kg)
10 mg/kg IV Azithromycin daily for 3 days
干预措施: Azithromycin 10 mg (Drug)
Azithromycin (20 mg/kg)
20 mg/kg IV Azithromycin daily for 3 days
干预措施: Azithromycin 20mg (Drug)
结局指标
主要结局
Nasal Total Matrix Metalloproteinase (MMP)-9 Level
时间窗: Day 3
To determine the concentration of total MMP-9 levels in the nasal compartment
Pharmacokinetic-Lung Half Life of AZM
时间窗: From baseline to 72 hours post treatment
Measurement of AZM half life in the lung
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
时间窗: 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
时间窗: From baseline to 72 hours post treatment
Measurement of AZM half life in the plasma
次要结局
- Duration of Mechanical Ventilation in Days(Pre-treatment through 2 weeks)
- Duration of BiPAP in Days(Pre-treatment through 2 weeks)
- Duration of PICU Stay in Days(Pre-treatment through 2 weeks)
- Duration of High Flow Nasal Cannula in Days(Pre-treatment through 2 weeks)
- Duration of Oxygenation in Days(Pre-treatment through 2 weeks)
- Duration of Hospitalization in Days(Pre-treatment through 2 weeks)
研究者
Michele Kong
Associate Professor
University of Alabama at Birmingham