Prednisolone Versus Dexamethasone for Croup: a Randomized Controlled Trial Colin M. Parker, MBChB, DCH, MRCPCH, FACEM,a,b Matthew N. Cooper, BCA, BSc, PhDc OBJECTIVES: The use of either prednisolone or low-dose dexamethasone in the treatment of abstract childhood croup lacks a rigorous evidence base despite widespread use. In this study, we compare dexamethasone at 0.6 mg/kg with both low-dose dexamethasone at 0.15 mg/kg and prednisolone at 1 mg/kg. METHODS: Prospective, double-blind, noninferiority randomized controlled trial based in 1 tertiary pediatric emergency department and 1 urban district emergency department in Perth, Western Australia. Inclusions were age .6 months, maximum weight 20 kg, contactable by telephone, and English-speaking caregivers. Exclusion criteria were known prednisolone or dexamethasone allergy, immunosuppressive disease or treatment, steroid therapy or enrollment in the study within the previous 14 days, and a high clinical suspicion of an alternative diagnosis. A total of 1252 participants were enrolled and randomly assigned to receive dexamethasone (0.6 mg/kg; n = 410), low-dose dexamethasone (0.15 mg/kg; n = 410), or prednisolone (1 mg/kg; n = 411). Primary outcome measures included Westley Croup Score 1-hour after treatment and unscheduled medical re-attendance during the 7 days after treatment. RESULTS: Mean Westley Croup Score at baseline was 1.4 for dexamethasone, 1.5 for low-dose dexamethasone, and 1.5 for prednisolone. Adjusted difference in scores at 1 hour, compared with dexamethasone, was 0.03 (95% confidence interval 20.09 to 0.15) for low-dose dexamethasone and 0.05 (95% confidence interval 20.07 to 0.17) for prednisolone. Re- attendance rates were 17.8% for dexamethasone, 19.5% for low-dose dexamethasone, and 21.7% for prednisolone (not significant [P = .59 and .19]). CONCLUSIONS: Noninferiority was demonstrated for both low-dose dexamethasone and prednisolone. The type of oral steroid seems to have no clinically significant impact on efficacy, both acutely and during the week after treatment. WHAT’S KNOWN ON THIS SUBJECT: Although dexamethasone at 0.6 mg/kg is aPerth Children’s Hospital, Perth, Australia; bJoondalup Health Campus, Perth, Australia; and cTelethon Kids an established evidence-based treatment of childhood croup (reducing Institute, The University of Western Australia, Perth, Australia hospital admissions, length of stay, and need for endotracheal intubation), Dr Parker conceptualized and designed the study, coordinated and supervised data collection, alternative corticosteroid regimes are in widespread use based on evidence from small studies and observational data. drafted the initial manuscript, and reviewed and revised the manuscript; Dr Cooper performed the statistical analysis of the data and reviewed and revised the manuscript; and both authors WHAT THIS STUDY ADDS: With our study, we confirm that prednisolone at approved the final manuscript as submitted and agree to be accountable for all aspects of 1 mg/kg and dexamethasone at 0.15 mg/kg are both noninferior to the work. dexamethasone at 0.6 mg/kg for the treatment of croup in children. We found no difference between groups for both acute croup severity and This trial has been registered with the Australian New Zealand Clinical Trials Registry (https://www. unscheduled medical re-attendance after treatment. anzctr.org.au/Trial/Registration/TrialReview.aspx?id = 83722) (identifier ACTRN12609000290291). DOI: https://doi.org/10.1542/peds.2018-3772 To cite: Parker CM and Cooper MN. Prednisolone Versus Dexamethasone for Croup: a Randomized Controlled Trial. Accepted for publication Jun 17, 2019 Pediatrics. 2019;144(3):e20183772 Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 144, number 3, September 2019:e20183772 ARTICLE The efficacy and safety of 1mg/kgpoforcroupinpatients urban EDs: Princess Margaret corticosteroids for the treatment of receiving intubation14 suggests that Hospital for Children (a tertiary croup has established their use as acomparableglucocorticoiddoseof pediatric center) and Joondalup routine therapy for the emergency dexamethasone (∼0.15 mg/kg) should Health Campus (an urban district department (ED) management of be equally effective.15 hospital). Hospital research ethics – croup,1 3 including, at our own committee approval was obtained at Prednisolone (1 mg/kg) has been institution, all ED attendances for both centers, and the study was 4 shown in 1 study to shorten the time croup. Steroid treatments have been registered with the Australian New to extubation for patients with croup shown to significantly decrease the rate Zealand Clinical Trials Registry in intensive care.14 Many centers of hospital admission, length of hospital (identifier ACTRN12609000290291). therefore use oral prednisolone for stay, return visits, endotracheal De-identified individual participant the ED management of croup as intubation, and admission to ICUs in data will not be made available. – a more readily available alternative to patients with croup.5 9 Although dexamethasone.16 The type and dose Participants different routes of corticosteroid of corticosteroid treatment of croup administration have been used, Patients were a convenience sample depends largely on geographic including nebulized, intramuscular, and of children presenting to either of the location because different centers intravenous dosing, the oral route has EDs with croup during the study preferentially administer different many advantages and is the preferred period (March 2009–July 2012). The drugs and doses. There have only route in many centers.10,11 The disease state was defined as a clinical been 3 small randomized controlled clinician treating children with croup diagnosis of croup (laryngotracheitis) trials used to compare oral may further consider the type and dose by the ED doctor after a history and dexamethasone with oral of oral steroid. 16 physical examination. If there was any prednisolone. Fifoot and Ting found diagnostic uncertainty, clinicians Although early trials revealed safety no difference between the 2 could refer to a Guidance for Doctors and efficacy with intramuscular treatments, and an earlier study by 17 information sheet (Supplemental dexamethasone at a dose of Sparrow and Geelhoed of 133 Information), in which a croup 0.6 mg/kg,6 subsequent studies children with mild to moderate croup diagnosis is defined as a hoarse voice revealed efficacy of oral revealed that children treated with or barking cough and stridor (with or dexamethasone,7 and there is evidence prednisolone (1 mg/kg po) were without increased work of breathing) that smaller doses of dexamethasone more likely to seek unscheduled directly observed or elicited in the (0.3and0.15mg/kgpo)maybe follow-up for medical care than history. Inclusion criteria were age fi 12 children treated with dexamethasone . equally ef cacious. The lower oral 18 6 months, contactable by telephone, dose of 0.15 mg/kg has been accepted (0.15 mg/kg po). Garbutt et al and English-speaking caregivers. A and implemented in some centers2; found no difference in duration of maximum weight of 20 kg was however, the limited number of croup symptoms or additional health imposed to limit the maximum supporting studies7,12 raises the care when comparing a single dose of possible dexamethasone dose to question of efficacy compared with dexamethasone with 3 days of 12 mg (adult dose). Exclusion criteria adoseof0.6mg/kgpo,9,13 particularly prednisolone treatment. included known prednisolone or around the power of these studies to In this study, we aim to compare the dexamethasone allergy, detect small, but clinically important, traditional, evidence-supported gold immunosuppressive disease or differences in outcomes. Notably, the standard croup treatment, treatment, steroid therapy or 12 studies by Geelhoed and Macdonald dexamethasone at a dose of enrollment in the same study within had only 80% power (at the 5% 0.6 mg/kg, with 2 alternate the previous 14 days, and a high fi signi cance level) to detect a doubling treatments already in widespread clinical suspicion of an alternative fi in the duration of hospitalization, use, namely lower-dose diagnosis, with speci c prompts to which would only reveal a relatively dexamethasone (0.15 mg/kg) and include bacterial tracheitis, inhaled large clinical difference between prednisolone (1 mg/kg), and assess foreign body, retropharyngeal treatments. On the other hand, the these treatments for noninferiority. abscess, epiglottitis, angioedema, lower dose is supported by almost 3 vascular ring, and subglottic stenosis. decades of clinical experience at our Signed consent was obtained from institution, indicating no rise in the rate METHODS caregivers by the treating doctor after of intubation or admission to intensive the doctor provided a standardized care after a reduction of the dose to Design information sheet (Croup Study: 0.15 mg/kg po.4 The well-proven We conducted a prospective, double- Information for Parents, see efficacy of prednisolone in a dose of blind, randomized controlled trial at 2 Supplemental Information). Downloaded from www.aappublications.org/news by guest on September 27, 2021 2 PARKER and COOPER Interventions second primary outcome was noninferiority (by using a 2-sided t a Patients were randomly assigned to 1 unscheduled medical re-attendance test; common SD of 1.8; = .05). (for any reason) during the 7 days The expected re-attendance rate for of 3 interventions: dexamethasone 4 (0.6 mg/kg; standard