Abstract
Background: Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease.
Methods: Between Nov 12, 2008, and Dec 23, 2010, we enrolled
Indigenous Australian, Maori, and Pacific Island children aged 1-8 years with
either bronchiectasis or chronic suppurative lung disease into a multicentre,
double-blind, randomised, parallel-group, placebo-controlled trial. Eligible
children had had at least one pulmonary exacerbation in the previous 12 months.
Children were randomised (1:1 ratio, by computer-generated sequence with
permuted block design, stratified by study site and exacerbation frequency [1-2
vs ?3 episodes in the preceding 12 months]) to receive either azithromycin (30
mg/kg) or placebo once a week for up to 24 months. Allocation concealment was
achieved by double-sealed, opaque envelopes; participants, caregivers, and
study personnel were masked to assignment until after data analysis. The
primary outcome was exacerbation (respiratory episodes treated with
antibiotics) rate. Analysis of the primary endpoint was by intention to treat.
At enrolment and at their final clinic visits, children had deep nasal swabs
collected, which we analysed for antibiotic-resistant bacteria. This study is
registered with the Australian New Zealand Clinical Trials Registry;
ACTRN12610000383066.
Findings: 45 children were assigned to azithromycin and 44 to placebo.
The study was stopped early for feasibility reasons on Dec 31, 2011, thus
children received the intervention for 12-24 months. The mean treatment
duration was 20.7 months (SD 5.7), with a total of 902 child-months in the
azithromycin group and 875 child-months in the placebo group. Compared with the
placebo group, children receiving azithromycin had significantly lower
exacerbation rates (incidence rate ratio 0.50; 95% CI 0.35-0.71; p<0.0001).
However, children in the azithromycin group developed significantly higher
carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those
receiving placebo (four of 37, 11%; p=0.002). The most common adverse events
were non-pulmonary infections (71 of 112 events in the azithromycin group vs
132 of 209 events in the placebo group) and bronchiectasis-related events
(episodes or investigations; 22 of 112 events in the azithromycin group vs 48
of 209 events in the placebo group); however, study drugs were well tolerated
with no serious adverse events being attributed to the intervention.
Interpretation: Once-weekly azithromycin for up to 24 months decreased
pulmonary exacerbations in Indigenous children with non-cystic-fibrosis
bronchiectasis or chronic suppurative lung disease. However, this strategy was
also accompanied by increased carriage of azithromycin-resistant bacteria, the
clinical consequences of which are uncertain, and will need careful monitoring
and further study.
Original language | English |
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Pages (from-to) | 610-620 |
Number of pages | 11 |
Journal | The Lancet Respiratory Medicine |
Volume | 1 |
Issue number | 8 |
DOIs | |
Publication status | Published - Oct 2013 |