Oral Prednisolone Dosing in Children Hospitalized With Asthma

• Sponsor: Children's Hospital of Philadelphia (Other)
• Overall Status: Completed
• CT.gov ID: NCT00257933
• Collaborator: (none)
• Enrollment: 152
• Location: 1
• Arms: 2
• Duration (Months): 9
• Patients Per Site Per Month: 16.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Prednisolone high dose; Drug: Prednisolone lower dose	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Oral Prednisolone Dosing in Children Hospitalized With Asthma
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Nov 1, 2006
• Actual Study Completion Date: Nov 1, 2006

Arms and Interventions

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: High Dose Prednisolone Oral steriod corticosteriods 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: Low dose Prednisolone Oral prednisolone Oral steriod corticosteriods asthma exacerbations

Outcome Measures

Primary Outcome Measures

1. 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

1. 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]

2. Time Spent in Each Severity Level of the Asthma Care Pathway [Time spent in each severity level of pathway]

3. The Rate and Degree of Change in Forced Expiratory Volume (FEV1) and Peak Expiratory Flow (PEF) Between Treatment Groups [Every 4 hours during hospitalization]

4. Differences in Clinical Asthma Symptom Scores During Hospitalization Between Treatment Groups [Every 4 hours during hospitalization]

5. Rate of Relapse Between Treatment Groups [2 weeks after hospitalization]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Children's Hospital of Philadelphia

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00257933
• Other Study ID Numbers: 2005-9-4377
• First Posted: Nov 24, 2005
• Last Update Posted: Dec 31, 2010
• Last Verified: Dec 1, 2010

• Keywords provided by , ,: Corticosteroids; Treatment; Pediatric
• Additional relevant MeSH terms: Asthma; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Study Results

Participant Flow

Arm/Group Title	High Dose Prednisolone	Lower Dose Prednisolone
Arm/Group Description	High dose prednisolone: 1 mg/kg of oral prednisolone (maximum 30mg) every 6 hours	Lower dose prednisolone: 1 mg/kg (maximum 30mg)of oral prednisolone every 12 hours alternating with placebo
Period Title: Overall Study
STARTED	74	78
COMPLETED	74	78
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	High Dose Prednisolone	Lower Dose Prednisolone	Total
Arm/Group Description	High dose prednisolone: 1 mg/kg of oral prednisolone (maximum 30mg) every 6 hours	Lower dose prednisolone: 1 mg/kg (maximum 30mg)of oral prednisolone every 12 hours alternating with placebo	Total of all reporting groups
Overall Participants	74	78	152
Age (Count of Participants)
<=18 years	74 100%	78 100%	152 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.9 (4.4)	7.0 (3.8)	7.4 (4.2)
Sex: Female, Male (Count of Participants)
Female	27 36.5%	27 34.6%	54 35.5%
Male	47 63.5%	51 65.4%	98 64.5%
Region of Enrollment (participants) [Number]
United States	74 100%	78 100%	152 100%

Outcome Measures

1. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Dose Prednisolone	Lower Dose Prednisolone
Arm/Group Description	High dose prednisolone: 1 mg/kg of oral prednisolone (maximum 30mg) every 6 hours	Lower dose prednisolone: 1 mg/kg (maximum 30mg)of oral prednisolone every 12 hours alternating with placebo
Measure Participants	74	78
Median (Inter-Quartile Range) [Hours]	35	33

2. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Time Spent in Each Severity Level of the Asthma Care Pathway
Time Frame	Time spent in each severity level of pathway

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Differences in Clinical Asthma Symptom Scores During Hospitalization Between Treatment Groups
Time Frame	Every 4 hours during hospitalization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Rate of Relapse Between Treatment Groups
Time Frame	2 weeks after hospitalization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	High Dose Prednisolone		Lower Dose Prednisolone
Arm/Group Description	High dose prednisolone: 1 mg/kg of oral prednisolone (maximum 30mg) every 6 hours		Lower dose prednisolone: 1 mg/kg (maximum 30mg)of oral prednisolone every 12 hours alternating with placebo
All Cause Mortality
	High Dose Prednisolone		Lower Dose Prednisolone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	High Dose Prednisolone		Lower Dose Prednisolone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/74 (0%)		0/78 (0%)
Other (Not Including Serious) Adverse Events
	High Dose Prednisolone		Lower Dose Prednisolone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/74 (0%)		0/78 (0%)

Limitations/Caveats

Limited ability to measure pulmonary function in hospitalized children with asthma did not allow measurement of this outcome. Some protocol violations occurred Single center study

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.