Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for
respiratory exacerbations in children (BEST-2): study protocol for a randomized
controlled trial.
Author(s): Chang AB(1), Grimwood K, Wilson AC, van Asperen PP, Byrnes CA, O'Grady KA, Sloots
TP, Robertson CF, Torzillo PJ, McCallum GB, Masters IB, Buntain HM, Mackay IM,
Ungerer J, Tuppin J, Morris PS.
Affiliation(s): Author information:
(1)Child Health Division, Menzies School of Health Research, Charles Darwin
University, Darwin, NT, Australia. annechang@ausdoctors.net
Publication date & source: 2013, Trials. , 14:53
BACKGROUND: Bronchiectasis unrelated to cystic fibrosis (CF) is being
increasingly recognized in children and adults globally, both in resource-poor
and in affluent countries. However, high-quality evidence to inform management is
scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for
non-severe respiratory exacerbations, because of the antibiotic-susceptibility
patterns detected in the respiratory pathogens commonly associated with
bronchiectasis. Azithromycin has a prolonged half-life, and with its unique
anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an
attractive alternative. Our proposed study will test the hypothesis that oral
azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at
achieving resolution of non-severe respiratory exacerbations by day 21 of
treatment in children with non-CF bronchiectasis.
METHODS: This will be a multicenter, randomized, double-blind, double-dummy,
placebo-controlled, parallel group trial involving six Australian and New Zealand
centers. In total, 170 eligible children will be stratified by site and
bronchiectasis etiology, and randomized (allocation concealed) to receive: 1)
azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2)
amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21
days as treatment for non-severe respiratory exacerbations. Clinical data and a
parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at
baseline, at the start and resolution of exacerbations, and on day 21. In most
children, blood and deep-nasal swabs will also be collected at the same time
points. The primary outcome is the proportion of children whose exacerbations
have resolved at day 21. The main secondary outcome is the PC-QOL score. Other
outcomes are: time to next exacerbation; requirement for hospitalization;
duration of exacerbation, and spirometry data. Descriptive viral and
bacteriological data from nasal samples and blood inflammatory markers will be
reported where available.
DISCUSSION: Currently, there are no published randomized controlled trials (RCT)
to underpin effective, evidence-based management of acute respiratory
exacerbations in children with non-CF bronchiectasis. To help address this
information gap, we are conducting two RCTs. The first (bronchiectasis
exacerbation study; BEST-1) evaluates the efficacy of azithromycin and
amoxycillin-clavulanate compared with placebo, and the second RCT (BEST-2),
described here, is designed to determine if azithromycin is non-inferior to
amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in
children with acute respiratory exacerbations.
TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR)
number http://ACTRN12612000010897.
http://www.anzctr.org.au/trial_view.aspx?id=347879.
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