Official Title: “Oral Prednisolone Dosing in Children Hospitalized With Asthma”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Efficacy Study

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.

Intervention(s) in this Clinical Trial

• Drug: Prednisolone high dose
  • 4 mg/kg/day orally divided every 6 hours (maximum 30 mg per dose)
• Drug: Prednisolone lower dose
  • 2 mg/kg/day orally divided q 12 (maximum 30mg/dose) alternating with placebo

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • High dose prednisolone
• Experimental: 2
  • Lower dose prednisolone

Primary Measures

• Time measured from the administration of the loading dose of prednisolone in the ED until the home dose of albuterol is administered.
  • Time Frame: Hospitalization
    Safety Issue?: No

Secondary Measures

• Time measured from the writing of the admission order until the writing of the discharge order.
  • Time Frame: Hospitalization
    Safety Issue?: No
• Time spent in each severity level of the asthma care pathway.
  • Time Frame: Hospitalization
    Safety Issue?: No
• The rate and degree of change in FEV1 and PEF between treatment groups.
  • Time Frame: Hospitalization
    Safety Issue?: No
• Differences in clinical asthma symptom scores during hospitalization between treatment groups.
  • Time Frame: Hospitalization
    Safety Issue?: No
• Rate of relapse between treatment groups.
  • Time Frame: 2 weeks after hospitalization
    Safety Issue?: 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 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 2 Years

Maximum Age for this Clinical Trial: 18 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Children's Hospital of Philadelphia

Overall Clinical Trial Officials and Contacts

Joseph J Zorc, MD Principal Investigator Children's Hospital of Philadelphia  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00257933

Study ID Number: 2005-9-4377

ClinicalTrials.gov Identifier: NCT00257933

Health Authority: United States: Food and Drug Administration