A Randomized Controlled Trial Comparing Epinephrine and Dexamethasone to Placebo in the Treatment of Infants With Bronchiolitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 864
- 试验地点
- 12
- 主要终点
- Admission to hospital for bronchiolitis within 7 days post enrollment
研究概览
简要总结
We hypothesize that infants with bronchiolitis treated with inhaled epinephrine in the Emergency Department (ED) and a 2-day course of oral dexamethasone will have fewer hospitalizations over 7 days compared to infants treated with placebo. To examine this hypothesis, we will conduct a phase III, multicentre, randomized, double-blind trial. Infants presenting to one of twelve study EDs will be enrolled to one of two study groups: (1) inhaled epinephrine and oral dexamethasone or (2) inhaled placebo and oral placebo. Our primary outcome will be admission for bronchiolitis by day 7 following the enrolment. As a planned secondary analysis, a between-group comparison of the primary outcome will be performed in those patients presenting with a first episode of bronchiolitis.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
All study personnel (including study nurses, coordinators, investigators, data management staff, and statistical team), health care staff providing patient care, and patients/families will be blinded to the study group assignment.
入排标准
- 年龄范围
- 60 Days 至 12 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Presenting to the ED with an episode of bronchiolitis. Bronchiolitis will be defined as an episode of wheezing or crackles in a child < 12 month of age associated with signs of an upper respiratory tract infection (e.g. cough, coryza, nasal congestion) during the period deemed to be peak season for RSV bronchiolitis (approximately December to April in Northern Hemisphere and June to October in Southern Hemisphere). We have chosen not to define bronchiolitis as the first episode of wheezing or crackles to better reflect the clinical guidelines and clinical practice internationally.
- •*Adjustment for COVID-19: The COVID-19 pandemic has resulted in unseasonal RSV and bronchiolitis seasons. As such, adjustments will be made to study recruitment to ensure recruitment occurs during peak RSV times. In order to achieve this aim, the study may in some sites recruit for 12 months of the year.
- •Age 60 days to less than 12 months. Children younger than 60 days will not be enrolled due to the risk of concomitant infection and other issues pertaining to glucocorticoid use in the very young. Children older than 12 months will not be enrolled to minimize the risk of enrolling children with asthma.
排除标准
- •Respiratory distress assessment instrument (RDAI) score of less than or equal to
- •This RDAI will ensure children with very mild respiratory diseases are not enrolled. This is the lower limit of the RDAI range used in CanBEST.
- •Previously known chronic disease that may affect cardiopulmonary status of the patient, such as bronchopulmonary dysplasia currently receiving oxygen, cystic fibrosis, congenital heart disease and immune deficiency. These children may be at higher risk for developing severe illness.
- •Severe respiratory distress evidenced by a sustained pulse rate > 200 beats/min, a sustained respiratory rate > 80 breaths/min, profound lethargy (as deemed by the treating physician), or requiring resuscitation room care. We will exclude these children as they are likely to be admitted due to severity of illness.
- •Presenting with symptoms of apnea prior to enrollment.
- •Treatment with oral, inhaled, or IV corticosteroids within the last 1 week.
- •History of adverse reaction to glucocorticoids.
- •Treatment with any beta-agonists (salbutamol/albuterol or epinephrine/adrenaline) in the ED prior to study enrolment.
- •Presence of varicella or recent (less than 3 weeks) close contact (defined as any household or daycare contact, or greater than 15 minutes of face to face contact, or greater than 1 hour of being in the same dwelling with an individual) without a history of prior infection. These patients are not enrolled to reduce any risk of developing severe varicella with corticosteroid use.
- •Insurmountable language barrier (patient's parent/guardian is unable to understand English or French to give informed consent and participate in follow-up).
- •Any child born at less than 37weeks gestation who is younger than 60 days corrected age. We will not enroll these children to lower any risk of exposing young infants to corticosteroids.
- •Previous enrolment in the trial.
- •Unavailability for follow-up period.
- •Certain admission to hospital.
研究组 & 干预措施
Active Intervention Arm
Oral dexamethasone and nebulized epinephrine OR Oral dexamethasone and inhaled epinephrine given by MDI
干预措施: Oral dexamethasone (Drug)
Active Intervention Arm
Oral dexamethasone and nebulized epinephrine OR Oral dexamethasone and inhaled epinephrine given by MDI
干预措施: Nebulized Epinephrine (Drug)
Active Intervention Arm
Oral dexamethasone and nebulized epinephrine OR Oral dexamethasone and inhaled epinephrine given by MDI
干预措施: MDI Epinephrine (Drug)
Control Arm
Oral placebo (OraBlendTM in Canada and a compounded oral placebo solution at New Zealand/Australia sites) and nebulized saline.
OR Oral placebo (OraBlendTM in Canada and a compounded oral placebo solution at New Zealand/Australia sites) and inhaled placebo given by MDI.
干预措施: Oral placebo (Drug)
Control Arm
Oral placebo (OraBlendTM in Canada and a compounded oral placebo solution at New Zealand/Australia sites) and nebulized saline.
OR Oral placebo (OraBlendTM in Canada and a compounded oral placebo solution at New Zealand/Australia sites) and inhaled placebo given by MDI.
干预措施: Nebulized normal saline (Drug)
Control Arm
Oral placebo (OraBlendTM in Canada and a compounded oral placebo solution at New Zealand/Australia sites) and nebulized saline.
OR Oral placebo (OraBlendTM in Canada and a compounded oral placebo solution at New Zealand/Australia sites) and inhaled placebo given by MDI.
干预措施: MDI placebo (Drug)
结局指标
主要结局
Admission to hospital for bronchiolitis within 7 days post enrollment
时间窗: 7 days post enrollment
1) patient being admitted to inpatient ward, or 2) an ED length of stay 12 hours or greater or 3) a combined ED and observation unit stay of 12 hours or greater.
次要结局
- Admission to hospital for bronchiolitis at the time of the enrollment ED visit(Enrollment visit)
- All cause admission to Hospital within 21 days following enrollment ED visit(up to 21 days post enrollment)
- Health Care related costs within the 21 days following enrollment ED visits.(up to 21 days post enrollment)
- All cause Health care provider visits (including ED visits) by day 21 following enrollment ED(up to 21 days post enrollment)
研究者
Amy Plint
MD, MSc, FRCPC, Research Chair in Pediatric Emergency Medicine
Children's Hospital of Eastern Ontario