Randomised control trial
Howard M. Corneli, M.D., et alA Multicenter, Randomized, Controlled Trial of Dexamethasone for Bronchiolitis
New England Journal of Medicine
July 26, 2007; 331-338
- Submitted by:Kara Cardenas - Medical Student
- Institution:Michigan State University College of Human Medicine
- Date submitted:14th August 2007
1
Objectives and hypotheses
1.1
Are the objectives of the study clearly stated?
Corticosteroids are commonly used to treat bronchiolitis, but there is limited evidence to support this practice. The aim of this study was to determine whether dexamethasone administration in children with a first episode of wheezing is efficacious.
2
Design
2.1
Is the study design suitable for the objectives
Yes, a double blind, RCT was used.
2.2
Who / what was studied?
Children between the ages of 2-12 months with a first episode of wheezing diagnosed with moderate to severe bronchiolitis in the ED were given either a single dose of dexamethasone (1 mg per kg of body weight) or a placebo.
2.3
Was this the right sample to answer the objectives?
Yes, 600 children were studied from 20 emergency departments over a three year period.
2.4
Is the study large enough to achieve its objectives? Have sample size estimates been performed?
Yes, a sample size was calculated in order to provide more than 80% power to detect an absolute reduction in hospital admission rates of 12% or more in the dexamethasone group.
2.5
Were all subjects accounted for?
Yes, all of the subjects were accounted for.
2.6
Were all appropriate outcomes considered?
Yes, hospital admission after four hours of observation in the emergency department was the primary outcome.
2.7
Has ethical approval been obtained if appropriate?
The IRB's at all sites approved the study.
2.8
Were the patients randomised between treatments?
Children were randomly placed in either the dexamethasone group or the placebo group.
2.9
How was randomisation carried out?
The children were randomized by computer using a telephone keypad for data entry.
2.10
Are the outcomes clinically relevant?
Yes, hospital admission was the primary outcome.
3
Measurement and observation
3.1
Is it clear what was measured, how it was measured and what the outcomes were?
The primary outcome was hospital admission after four hours of emergency department observation. Later outcomes were also evaluated including length of hospital stay, later medical visits or admissions, and adverse events.
3.2
Are the measurements valid?
The authors do not state how the validity of the study was assessed.
3.3
Are the measurements reliable?
This study is consistent with several other studies on dexamethasone use in this study population.
3.4
Are the measurements reproducible?
The study methods were clearly outlined. The inclusion and exclusion criteria were clearly stated.
3.5
Were the patients and the investigators blinded?
Children were placed into either the dexamethasone or the placebo group by computerized randomization. All emergency department staff, study personnel, and parents/guardians were unaware of the group assignments.
4
Presentation of results
4.1
Are the basic data adequately described?
Yes, data is clearly presented.
4.2
Were groups comparable at baseline?
Yes, all of the children in the study were between the ages of 2 and 12 months of age with a first episode of wheezing diagnosed as moderate to severe bronchiolitis in the emergency department. Other baseline characteristics such as age, sex, vital signs, and personal and family history were comparable.
4.3
Are the results presented clearly, objectively and in sufficient detail to enable readers to make their own judgement?
Yes, Figures and Tables clearly presented
4.4
Are the results internally consistent, i.e. do the numbers add up properly?
Yes
4.5
Were side effects reported?
Adverse events were recorded. Vomiting within 20 minutes after administration of the study medication occurred in 5.5% of the dexamethasone group and 4.7% of the placebo group. None of the infants had GI bleeding, hypertension, or complicated varicella. Pneumonia occurred in 3 of the infants. 2 of these infants were in the placebo group, one of whom developed an empyema.
5
Analysis
5.1
Are the data suitable for analysis?
Yes
5.2
Are the methods appropriate to the data?
Yes, dexamethasone group was compared to a placebo and hospital admission rates were used as the primary outcome.
5.3
Are any statistics correctly performed and interpreted?
Yes, hospital admission rates were compared with Pearson's chi-square test. The RACS was compared in the two groups by means of a two-sample t-test.
6
Discussion
6.1
Are the results discussed in relation to existing knowledge on the subject and study objectives?
Yes, findings were consistent with several other studies that failed to demonstrate the efficacy of corticosteroids in bronchiolitis. A collective review of the Cochrane Collaboration of 13 studies of the use of corticosteroids for bronchiolitis showed no significant difference in outcome between corticosteroid and placebo groups. Only one study documented a difference between the two groups.
6.2
Is the discussion biased?
There is no apparent bias in the discussion.
7
Interpretation
7.1
Are the authors' conclusions justified by the data?
The data clearly showed no difference between corticosteroids and placebo in reducing the rate of hospital admission.
7.2
What level of evidence has this paper presented? (using CEBM levels)
1a
7.3
Does this paper help me answer my problem?
Yes, this paper indicates that it is not efficacious to give a dose of dexamethasone in the ED to children between the ages of 2 and 12 months with a first episode of wheezing diagnosed as moderate to severe bronchiolitis.
8
Implementation
8.1
Can any necessary change be implemented in practice?
For children that fit the study criteria, dexamethasone has no effect on the child's outcome.
8.2
What aids to implementation exist?
Many academic centers have stopped using dexamethasone already.
8.3
What barriers to implementation exist?
A subgroup of children with recurrent wheezing might still benefit from the dexamethasone (these patients were excluded from the study).