Group 3

Rizki Fauzia
Tata Dimas Al Haq
Winda Yunisah
1a. Identification as a randomized trial in tittle
• Nebulized budesonide for children with mild to-moderate group
1b. Structure summary of trial design,
methods, result, and conclutions
• Summary of trial design : this randomized double blind
trial compared a nebulized gluccocorticoid budesonide
with placebo in outpatient wit mild to moderate group
• Methods : the patients were randomly assigned to receive
either2mg (4ml) of nebulizedbudesonide (27 children)
they were then assessed hourly for up to four hours by
investigators who were unaware of the assihned
treatment
• Result : at the final study asessment, the median score
was significantly lower in the budesonide group than in
placebo group.
• Conclution : nebulized budesonide leads to a prompt and
important clinical improvement in children with mild to
moderate group who come to theemergency
departement
INTRODUCTION
2A BACKGROUND
2B OBJECTIVES
2a. Scientific background and explanation of
rationale
• What is known : after several decades of debate ,
the benefit of glucocorticoid therapy in patients
hospitalized for croup has been firmly established
by the results of fourrecent randomized clinical
tgrials of intramuscular dexamethasone oral
prednisolone and nebulized budesonide.
• What is unknown : it is not know , however
whether treatment at an early stage of the illness
would reduce the severity of the clinical
symtoms, prevent hospitalization or prolonged
visits to the emergency departement and thereby
both improve health outcomes and reduce costs
2b. Specific objectives or hypotheses
• We designed a randomized, placebo-controlled trial to determine
whether nebulizede budesonide leads to a clinically important
improvement in respiratory symptoms whitin for hours for children
with mild to moderate coup who come to the emergency
departement
METHODS
3A, 3B TRIAL DESIGN
4A PARTICIPANTS
5 INTERVENTION
6A 6B OUTCOMES
7A 7B SAMPLE SIZE
3a. Description of trial design
(such as parallel, factorial)
including allocation ratio
3b. Important changes to methods
after trial commencement (such
as eligibility criteria), with reasons
• While the patients remained in the emergency
departement, they wereassessed by the
research assistant every hour for four hours
until the coup score was 1 or less or until the
croup patient well enough to be sent home
4a. Eligibility criteria for participants
• Inclusion criteria : …were eligible for the study if they met the
following criteria ; an age of three months to five years; a syndrome
consisting of hoarseness , inspiratory stridor, and barking cough , and
a croup score of 2or higher after breathing humidified oxygen for at
least 15 minutes
• Exclution criteria : patients were excluded if they had been given a
diagnosis of epiglotitis or chronic upper or lower airway disease (not
incluiding asthma), if corticosteroids has been administered within
the preceding two weeks or if they had severe croup
4b. Settings and locations where
the data were collected

• Patients coming to the emergency

departement at the Children’s Hospital of
eastern Ontario between October 1, 1992 and
october 15 1993
5. The interventions for each group with
sufficient details allow replication,
including how and when they were
actually administered
• Eligible patients were randomly assigned receive a single
dose containing either 2 mg (4ml) of budesonide solution
(pulmicort, astra, pharma, missussauga , Ont) or 4 ml of
0.9 percent saline solution, administered by an updrafit
nebulizer with a continuous flow of oxygen at 5 to 6 liters
per minute.
• Because budesonide is slightly oppaque, yhe pharmacy
provided both budesonide and normal saline in opaque
brown syringes toensure blinding. The research assistant
then placed the study drug directly into an oppaque
nebulizer reservoir. Once nebulized , the study drug were
indistinguisable by sight and smell when tested before
and during the study
6a. Completely defined pre-
specified primary and secondary
outcome measures, including how
and when they were assessed
• All the patients underwent base line clinical
assessment by a research , consisting of determination
of the croup score, respiratory rate and heart rate
while the patient breathed humidified oxygen or was
inside a plastic enclosure (a croup tent)
• This global assesment of change was then evaluated
on a 15 point Likert scale ranging from -7 (a very great
deal worse) to +7 (a very great deal better) with 0
representing no change.
6b. Any changes to trial outcomes after the
trial commenced, with reasons
7a. How sample size was determined
• We estimated that 40 percent of the patients assigned toplacebo
would have clinically important improvements, as compared with 70
percent of those assigned to budesonide.
7b. When applicable, explanation
of any interim analyses and
stopping guidelines
• Because this changes in clinical practice
impaired our ability to recruit eligible patients
and to evaluate the independent effect of
budesonide, the study was stopped before the
specified sample was reached and before the
data was analyzed
8a. Method used to generate the random
allocation sequence
• Likert scale ranging from -7 (“a very great deal worse”) to +7 (“a very
great deal better”), with 0 representing no change.
8b. Type of randomization;details of any
restriction (such as blocking and block size)
9. Mechanism used to implement the random
allocation sequence
10. Who generated the random allocation, who
enrolled participants, and who assigned
participants to intervention
• Three research assistant trained by the investigator were on call to
enroll patient in the study between 9 a.m. and midnight everyday
except holiday.
• All the patients underwent base-line clinical assessment by a research
assistant.
• Randomization was performed in blocks of 10 by the pharmacy
department, with a random-number table.
• Thus, all treatment decisions during the weel after enrollment were
made by people unaware of the patient’s treatment assignment.
11a. If done, who was blinded after
assignment to interventions
11b. If relevant, description of the similarity
of intervention
• To prevent the clinical trial from interfering with usual clinical
practice, the treating physcicians were free to use other
interventions, such as racemic epinephrine of dexamethasone, or to
place a patient in a croup tent for dhe delivery of humidified oxygen.
12a. Statistical method used to compare
groups for primary and seconday outcomes
• ...Differences between groups were tested with the Mantel-Haenszel
test.
12b. Methods for additional analyses, such as
subgroup analyses and adjusted analyses
13a. For each group, the number of participants
who ere randomly assigned, recived intended
treatment, and were analysed for the primary
outcome
13b. For each group, losses and exclusions
after randomization, together with reasons
Result
14a Dates defining the periods of recruitment and follow up
• Patients coming to the emergency department at the Children's
Hospital of Eastern Ontario between October 1, 1992, and October
15, 1993,
• At the one-week follow-up, family members of all the patients in the
trial were contacted by telephone.
14b why the trial ended or was stopped

During the trial, however, the clinicians in the emergency department

came to consider the administration of dexamethasone to be the
standard of care for children with croup that remained symptomatic
after therapy with a mist stick. Because this change in clinical practice
impaired our ability to recruit eligible patients and to evaluate the
independent effect of budesonide, the study was stopped before the
specified sample was reached and before the data were analyzed.
15 a table showing baseline demograpic and the clinical characteristic
for each group
• 16. for each group,number of participant (denominator) included in each
analysis and whether the analysis was by original assigned groups
• During the study period, 390 patients had a diagnosis of croup on discharge
from the emergency department. Of these patients, 163 presented at
times when the study team was not on call, and in 24 additional cases the
emergency department failed to contact the study team. A further 146
patients did not meet the eligibility criteria for the study because they had
croup that was too mild (88 patients), did not meet the age requirement
(31 patients), did not meet our definition of croup (16 patients), had croup
that was too severe (5 patients), had epiglottitis (3 patients), had previous
upper airway disease (2 patients), or had recently been treated with
steroids (1 patient). The parents of the remaining 57 patients were
approached about participation in the study, and 54 agreed on behalf of
their children.
• 17a for each primary and secondary outcome, result for each group,
and the estimated effect size its prcision (such as 95% confidence
interval )
• When the a priori definition of response was used, at four hours 19 of
the budesonide group had a response (70 percent), as compared with
10 of the placebo group (37 percent) (P = 0.03).
• 19. all important harms, side effect, adverse event
• No adverse events were noted in the budesonide group. No patient in
that group had clinical deterioration, either in the emergency
department or after discharge. One patient in the placebo group had
a burning sensation on the face.
• 21 generalisability
Our study has generated data on both validity and responsiveness by
showing that the croup score correlates with the global judgments of
three groups of independent observers who have different perspectives
on the patient.
• Intrepretation consistent with result, balancing benefits and harms
and considering otherr relevant evidence
We conclude that nebulized budesonide is an effective initial therapy
for children with mild-to-moderate croup who come to the emergency
department and remain symptomatic after mist therapy. With its rapid
action and prolonged effect, budesonide may be a valuable agent for
inhibiting the subglottic inflammatory edema that contributes to
stridor in children with croup
Registration number and name of trial
registry
• From the Department of Pediatrics, University of Ottawa, Ottawa,
Ont. (T.P.K., L.K.W., T.S.); Scarborough Grace Hospital, Scarborough,
Ont. (M.E.F.); and the Department of Pediatrics, Johns Hopkins
University, Baltimore (P.C.R.).
• Address reprint requests to Dr. Rowe at the Department of Pediatrics,
Johns Hopkins Hospital, 600 N. Wolfe St./Brady 212, Baltimore, MD
21287.
Where the full trial protocol can be accessed
if available
• www.nejm.org
• Source of funding and other support
• Supported by a grant (04440) from the Ontario Ministry of Health.
• We are indebted to Pat Harman and Joanne Momy for their tireless
work as research assistants, to Colline Blanchard for randomization
and drug preparation, to Dr. Marilyn Li and all the pediatricians and
nurses in the Emergency Department for help in recruiting patients,
to Dr. Martin Osmond and Grace Dueck for their critical review of an
earlier version of this manuscript, and to Robert Stenstrom for
assistance with the early development of this project.