AZithromycin Therapy in Preschoolers With a Severe Wheezing Episode Diagnosed at the Emergency Department (AZ-SWED)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 840
- 试验地点
- 16
- 主要终点
- Asthma Flare-up Diary for Young Children
研究概览
简要总结
AZ-SWED is a parallel group, double blind, placebo control efficacy clinical trial with two separate hypotheses. The trial compared the 5-day outcome of preschool children presenting to an Emergency Department (ED) with an acute, severe wheezing episode and treated with either once daily oral Azithromycin (12 mg/kg/day for 5 days) or placebo. The AZ-SWED researchers made separate comparisons in children in whom specific pathogenic bacteria isolated from nasopharyngeal swabs, and in those in whom they were not isolated. The primary outcome was the Asthma Flare-up Diary for Young Children (ADYC), a validated instrument that caregivers will transmit electronically daily after discharge from the ED. Families were contacted daily during the five-day treatment to collect the ADYC, and to assess compliance and complications. A randomly chosen subset of enrolled children participated in two follow-up visits 5-8 days and 14-21 days after visit 1 to assess development of resistance to study drug and treatment response related changes in the airway microbiome.
详细描述
This Phase III trial is designed as a parallel group, placebo-controlled, double-blind, randomized, multi-center evaluation of AZ for the treatment of acute wheezing episodes. The study recruited eligible patients from seven EDs. We tested two primary hypotheses: 1) AZ (12 mg/Kg/day) given for 5 days to preschool children with severe acute wheezing and harboring any of three specific pathogenic bacteria (H influenzae, M catarrhalis, or S pneumonia) in their nasopharynx will decrease the severity of the acute episode; and 2) AZ given on an identical schedule and dose will decrease the severity of wheezing episodes in children who do not harbor any of these three pathogenic bacteria in their nasopharynx.
This study had three visits. All enrolled patients participated on the Day 0 visit for screening, the informed consent process, enrollment, randomization, treatment initiation and dispensing drug. A sub-group of randomly selected patients participated in two follow-up visits on Day 5 - 8 and Day 14 - 21 where they were tested for antibiotic resistance.
The primary outcome was the sum of the Asthma Flare-up Diary for Young Children (ADYC) score, a validated instrument completed by the parent or guardian of the enrolled children during the 5-day treatment period. Secondary outcomes will include (1) ED length of stay (2) hospital length of stay, and (3) return ED visits or hospitalizations within 72 hours after randomization.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Equal allocation randomization tables were provided by the Data Coordinating Center (DCC) to the central research pharmacy. The central research pharmacy prepared consecutively numbered study kits according to the randomization schedule. Study kits were sent to the clinical sites.
Study products were labeled with numerical codes that maintained allocation concealment. Blinding/labeling of study medication bottles were completed at the site pharmacy prior to dispensing to the patient.
Randomization tables were created at the Data Coordinating Center using permuted-block randomization stratified by clinical site and baseline severity of symptoms. Permuted blocks of random lengths 2, 4, and 6 were used. The randomization number was recorded in the database.
入排标准
- 年龄范围
- 18 Months 至 60 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 months to <60 months.
- •The presence of expiratory wheezing as ascertained by a physician or nurse practitioner at admission to the ED.
- •A Pediatric Respiratory Assessment Measurement (PRAM) score of greater than or equal to 4 at any time during the ED admission.
排除标准
- •Presence of acute infection that requires systemic antibiotics, as determined by the physician.
- •Current or previous use of systemic antibiotics within the last 2 weeks.
- •Current or previous use of a steroid for wheezing within the last 2 weeks.
- •Suspected foreign body induced aspiration during the last 2 weeks.
- •A known systemic illness (other than allergy) including but not limited to:
- •Recurrent seizures
- •Gastroesophageal reflux (GER) requiring medical treatment
- •Major congenital anomalies
- •Physical and intellectual delay
- •Cerebral palsy
- •A history of chest surgery
- •Tuberculosis or other chronic infections
- •Primary or secondary immunodeficiency
- •Gastrointestinal malformation or disease
- •Cardiac disorder (except for a hemodynamically insignificant atrial septal defect (ASD), ventricular septal defect (VSD) or benign heart murmur)
- •Born at less than 36 weeks estimated gestational age.
- •Received oxygen for more than 5 days in the neonatal period, or received invasive mechanical ventilation.
- •Significant developmental delay / failure to thrive, defined as a child plotting less than 3rd percentile.
- •Any chronic lung disease.
- •The study intervention poses undue risk to patient in the opinion of the treating physician
- •Known sensitivity or allergy to AZ.
- •Participation in the evaluation of a drug or medical device currently or within the last 30 days.
- •Previous enrollment into this trial.
- •Inability of the parent or guardian to speak English or Spanish.
- •Positive PCR or antigen test for COVID-19 from hospital/doctor's office/testing center within the past 30 days.
研究组 & 干预措施
Treatment - Placebo
Eligible patients were randomly assigned to the placebo arm, per the randomization schedule (1:1).
干预措施: Placebo (Drug)
Treatment - Active
Eligible participants were randomly assigned to the Azithromycin arm (1:1)
干预措施: Azithromycin (Drug)
结局指标
主要结局
Asthma Flare-up Diary for Young Children
时间窗: 5 day course of azithromycin
The Asthma Flare-up Diary for Young Children (ADYC) is a validated instrument that consists of a 17-item questionnaire scored from 1 (best) to 7 (worst). The parent or guardian of the enrolled child (up to 60 months of age) will fill out the diary daily for 5 days, starting from the first day following the first dose of Azithromycin (AZ). The cumulative score at the end of 5 days will be used to assess response to the intervention (e.g. time to exacerbation, acute-care visit, hospitalization and no wheeze), with a higher score indicating a worse outcome.
次要结局
- Length of Stay(72 hours after randomization)
- Number of participants that develop Azithromycin resistant organisms(21 days after randomization)
研究者
Fernando Martinez
Regents' Professor
University of Arizona