Clinical Trial of Fluticasone Versus Placebo at the Onset of a Cold for Children With Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to determine, in children aged 1 to 6 years with recurrent
      asthma induced by upper respiratory tract infections (URTI), whether the administration of
      high doses of inhaled fluticasone started at the onset of symptoms of a cold will result in a
      reduced severity and shorter duration of asthma exacerbations and will not be associated with
      reduced growth velocity, osteopenia, and adrenal suppression.
    

Detailed description: 
      Preschool-aged children, who represent over half of asthmatics presenting to a pediatric
      emergency department with acute asthma, also account for most hospital admissions for
      pediatric asthma. More than 80% of exacerbations of preschool-aged children are triggered by
      upper respiratory tract infections (URTIs). Current management of this condition is clearly
      unsatisfactory. In most cases, there is a 24-48 hour delay between the first signs of a viral
      infection and the onset of asthmatic symptoms, suggesting that a window of opportunity where
      an intervention could be initiated to alter the severity of the asthma exacerbation. Prior
      trials testing chronic inhaled steroids throughout the viral season failed to demonstrate any
      benefit while those examining episodic inhaled steroids at onset of URTI reported a modest
      benefit on duration and severity of symptoms. The selection of children with mild
      exacerbations, the small sample size, the cross-over design, the short study period, and the
      relatively low doses of inhaled steroids may have limited the magnitude of observed benefits
      attributable to episodic treatment.

      The aim of this multicentre double-blind parallel-group placebo-controlled randomized trial
      is to compare the effectiveness of high doses (750 ug bid) of inhaled fluticasone with HFA
      propellant versus placebo started at the onset of a viral illness in attenuating the severity
      and duration of URTI-induced asthma in young children during a 12-month study period.
      Children aged 1 to 6 years with at least 2 URTI-induced asthma of moderate severity, i.e.
      requiring a short course of systemic steroids, in the previous 12 months or 1 in the previous
      6 months, and no inter-current symptoms will be selected for inclusion. Fluticasone 250 ug or
      placebo will be administered at a dose of 3 puffs BID from the onset of viral illness until
      48 hours without asthma symptoms for a maximum of 10 days. This dose was chosen to approach
      the efficacy of systemic steroids with significantly less adverse effects. Inhaled salbutamol
      will be administered as bronchodilator on an "as needed" basis for relief of asthma symptoms
      at a dose of 2 to 4 puffs of 100 ug at 4-hour interval or longer. A 7-day run-in period will
      serve to (1) establish the absence of chronic symptoms and the infrequent use of salbutamol
      and (2) obtain confirmation of eligibility by the pharmacy reports of all corticosteroid
      preparation dispensed in the preceding 12 months. Eligible children will receive baseline
      measurement of IgE as measure of atopy, varicella antibodies and of the safety parameters,
      including height, basal cortisol, and lumbar bone density. Children will then be randomly
      allocated to one of the two treatments in blocks of 4 with stratification on type of spacer
      (with mask or with mouthpiece) and recruitment site. Children will be followed every 3±1/2
      months by the site investigators or delegates until the end of the 12-month study period. The
      primary endpoint is the proportion of URTIs in each group requiring treatment with systemic
      corticosteroids as confirmed by review of medical records and pharmacy records of
      prescriptions dispensed. Secondary endpoints include other measures of the severity and
      duration of exacerbations, adjusted for the number of URTIs experienced by each child during
      the study period. Compliance with the study drug and the use of salbutamol (an important
      measure of severity) will be documented by the Doser, a device attached to the study inhalers
      which records, in a blinded mode, the date and number of doses administered over a 45-day
      period. The safety profile will be examined with the growth velocity, the basal cortisol, and
      the change in lumbar bone density between baseline and the end of the study period.

      A clinically important reduction in the severity and duration of viral-induced asthma will
      lead to other trials to establish the lowest effective dose of fluticasone. If no adverse
      effects on growth, bone density, and adrenal function are detected with the tested dose,
      safety may be assumed at lower doses. An absence of benefit will lead to the abandonment of
      this frequently used treatment strategy to consider alternative therapies for young children
      with URTI-induced asthma, who contribute to a marked proportion of health care spending.

      An upper respiratory tract infection is defined as rhinorrhea, nasal congestion, sore throat,
      ear ache, with or without fever, lasting >=48 hours.

      URTI-induced asthma is defined by wheezing in association with an URTI.
    

Intervention name(s): inhaled fluticasone 750 mcg/day twice daily until 2 days without symptoms (maximum 15 consecutive days)
Intervention type(s): Drug
Intervention MeSH terms: Fluticasone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: asthma; preschool; viral; upper respiratory track infection; fluticasone; inhaled corticosteroids; placebo; exacerbations; severity; safety; growth; bone mineral density; adrenal function; rescue beta2-agonists