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 Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Prednisolone high dose; Drug: Prednisolone lower dose

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.

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; High dose prednisolone	Drug: Prednisolone high dose; 4 mg/kg/day orally divided every 6 hours (maximum 30 mg per dose); Other Names: corticosteriods; High Dose Prednisolone; Oral steriod; asthma exacerbations
Experimental: 2; Lower dose prednisolone alternating with placebo	Drug: Prednisolone lower dose; 2 mg/kg/day orally divided q 12 (maximum 30mg/dose) alternating with placebo; Other Names: corticosteriods; Oral steriod; asthma exacerbations; Low dose Prednisolone; Oral prednisolone

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Investigators: Principal Investigator: Joseph J Zorc, MD, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): November 1, 2006
• Study Completion (Actual): November 1, 2006

Study Registration Dates

• First Submitted: November 22, 2005
• First Submitted That Met QC Criteria: November 22, 2005
• First Posted (Estimate): November 24, 2005

Study Record Updates

• Last Update Posted (Estimate): December 31, 2010
• Last Update Submitted That Met QC Criteria: December 23, 2010
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: Treatment; Pediatric; Corticosteroids
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: 2005-9-4377