Asthma
Conditions
Keywords
Corticosteroids, Treatment, Pediatric
Brief summary
This study hopes to determine the appropriate oral steroid dose for treating children hospitalized with asthma exacerbations. Practice guidelines from different countries recommend a wide range of doses, and the doses used in actual practice vary widely. There is no data on what is the most appropriate dose of prednisone (or equivalent) in this situation. We will be looking at the dose recommended by the National Asthma Education and Prevention Program guidelines, which are published by the National Heart, Lung, and Blood Institute, as compared with a lower dose which is commonly used in practice. We hypothesize that the lower dose will be no worse than the higher dose as determined primarily by duration of hospitalization.
Detailed description
Practice guidelines for the management of asthma in children universally recommend systemic corticosteroids for the treatment of moderate to severe asthma exacerbations. However, these guidelines vary widely with respect to dose, frequency, method of delivery, and duration of therapy. In actual practice, there is also considerable variation among clinicians in terms of corticosteroid dosing in children hospitalized with asthma exacerbations. At the Children's Hospital of Philadelphia (CHOP) the current standard is to use an initial dose of 4.0 mg/kg/day (1.0 mg/kg every 6 hours to a maximum of 30 mg/dose) although many other pediatric hospitals use a 2.0 mg/kg/day dose (1.0 mg/kg every 12 hours to a maximum of 30 mg/dose). Systematic reviews of the literature have called for a clinical trial to evaluate the effect of different doses of corticosteroids in treating pediatric asthma patients hospitalized with exacerbations. This study will use a randomized, double-blind, controlled trial design in order to compare the efficacy of two different steroid doses in resolving acute exacerbations of asthma in hospitalized children. Children being hospitalized for asthma exacerbations from the CHOP emergency department (ED) will be eligible for study enrollment. Those that meet enrollment criteria will be randomized to receive prednisolone either in the higher dose (1.0 mg/kg (max 30 mg) every 6 hours), or the lower dose (1.0 mg/kg (max 30 mg) every 12 hours and placebo doses at 6 hour intervals in between) for the first 48 hours of hospitalization. Once 48 hours has past, all patients still hospitalized will receive 1.0 mg/kg (max 30 mg) every 12 hours for the duration of hospitalization. Approximately 156 patients with 78 in each arm of the study will be enrolled. This study should be completed in six to eight months. A non-inferiority study design will be used. The primary outcome will be duration of hospitalization, as determined by duration of time elapsed from first dose of prednisolone administered in the emergency department (ED) until the discharge dose of albuterol is administered. Secondary outcomes will include time elapsed from the time the admission order is written until the discharge order is written, time spent in each severity level of the asthma care pathway, degree and rate of improvement in forced expiratory volume in one second (FEV1), improvement in peak expiratory flows (PEF), improvement in asthma symptom scores, and rate of relapse after discharge.
Interventions
4 mg/kg/day orally divided every 6 hours (maximum 30 mg per dose)
DRUGPrednisolone lower dose
2 mg/kg/day orally divided q 12 (maximum 30mg/dose) alternating with placebo
Sponsors
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Physician-diagnosed asthma with at least two previous visits to ED or primary care provider for asthma care * Clinical decision by ED attending physician to admit to Acute Care Unit (ACU) after standardized initial ED treatment
Exclusion criteria
* Clinical decision to begin continuous intravenous beta-agonist infusion * Clinical decision to begin intravenous methylprednisolone therapy * Clinical decision to admit to the Pediatric Intensive Care Unit * Other concurrent disease such as sickle cell disease, cystic fibrosis, or cardiac disease * Any contraindication to corticosteroid administration * Any systemic corticosteroid treatment within two weeks of presenting to the ED * Potential subjects will be excluded if informed consent is not obtained
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time Measured From the Administration of the Loading Dose of Prednisolone (2mg/kg up to Max 60mg) in the Emergency Department (ED) Until the Home Dose of Albuterol is Administered | Median time from loading dose to home dose of albuterol |
Secondary
| Measure | Time frame |
|---|---|
| Time Measured From the Writing of the Admission Order Until the Writing of the Discharge Order | Mean time from writing admit order until discharge order |
| Time Spent in Each Severity Level of the Asthma Care Pathway | Time spent in each severity level of pathway |
| The Rate and Degree of Change in Forced Expiratory Volume (FEV1) and Peak Expiratory Flow (PEF) Between Treatment Groups | Every 4 hours during hospitalization |
| Differences in Clinical Asthma Symptom Scores During Hospitalization Between Treatment Groups | Every 4 hours during hospitalization |
| Rate of Relapse Between Treatment Groups | 2 weeks after hospitalization |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High Dose Prednisolone High dose prednisolone: 1 mg/kg of oral prednisolone (maximum 30mg) every 6 hours | 74 |
| Lower Dose Prednisolone Lower dose prednisolone: 1 mg/kg (maximum 30mg)of oral prednisolone every 12 hours alternating with placebo | 78 |
| Total | 152 |
Baseline characteristics
| Characteristic | Lower Dose Prednisolone | High Dose Prednisolone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 78 Participants | 74 Participants | 152 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 7.0 years STANDARD_DEVIATION 3.8 | 7.9 years STANDARD_DEVIATION 4.4 | 7.4 years STANDARD_DEVIATION 4.2 |
| Region of Enrollment United States | 78 participants | 74 participants | 152 participants |
| Sex: Female, Male Female | 27 Participants | 27 Participants | 54 Participants |
| Sex: Female, Male Male | 51 Participants | 47 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 74 | 0 / 78 |
| serious Total, serious adverse events | 0 / 74 | 0 / 78 |
Outcome results
Primary
Time Measured From the Administration of the Loading Dose of Prednisolone (2mg/kg up to Max 60mg) in the Emergency Department (ED) Until the Home Dose of Albuterol is Administered
Time frame: Median time from loading dose to home dose of albuterol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High Dose Prednisolone | Time Measured From the Administration of the Loading Dose of Prednisolone (2mg/kg up to Max 60mg) in the Emergency Department (ED) Until the Home Dose of Albuterol is Administered | 35 Hours |
| Lower Dose Prednisolone | Time Measured From the Administration of the Loading Dose of Prednisolone (2mg/kg up to Max 60mg) in the Emergency Department (ED) Until the Home Dose of Albuterol is Administered | 33 Hours |
Secondary
Differences in Clinical Asthma Symptom Scores During Hospitalization Between Treatment Groups
Time frame: Every 4 hours during hospitalization
Secondary
Rate of Relapse Between Treatment Groups
Time frame: 2 weeks after hospitalization
Secondary
The Rate and Degree of Change in Forced Expiratory Volume (FEV1) and Peak Expiratory Flow (PEF) Between Treatment Groups
Time frame: Every 4 hours during hospitalization
Secondary
Time Measured From the Writing of the Admission Order Until the Writing of the Discharge Order
Time frame: Mean time from writing admit order until discharge order
Secondary
Time Spent in Each Severity Level of the Asthma Care Pathway
Time frame: Time spent in each severity level of pathway