Trial reportLancet (London, England)2018
Amoxicillin-clavulanate versus azithromycin for respiratory exacerbations in children with bronchiectasis (BEST-2): a multicentre, double-blind, non-inferiority, randomised controlled trial.
Trial report in Lancet (London, England), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Efficacy and safety of macrolides in the treatment of children with bronchiectasis: a meta-analysis.Pediatric research · 2023Pooled it
- Efficacy of oral amoxicillin-clavulanate or azithromycin for non-severe respiratory exacerbations in children with bronchiectasis (BEST-1): a multicentre, three-arm, double-blind, randomised placebo-controlled trial.The Lancet. Respiratory medicine · 2019Trial
- Neutrophil-related gene expression profile is associated with future paediatric bronchiectasis exacerbations.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Improving asthma control assessment and outcomes in children with asthma using an artificial intelligence digital tool: a prospective multicentre cohort study.ERJ open research · 2026Article
- Improving the management and outcomes of preschool wheeze: protocol of a prospective multicentre cohort study.BMJ open respiratory research · 2026Article
- Mechanisms, Efficacy, Safety, and Pharmacoeconomics of Low-Dose, Long-Term Macrolide Antibiotics in the Treatment of Chronic Obstructive Pulmonary Disease: A Review.International journal of chronic obstructive pulmonary disease · 2026Review
- Lung function trajectories in children with early diagnosis of non-cystic fibrosis bronchiectasis: a retrospective observational study.Italian journal of pediatrics · 2024Observational
- Evidence-based management guidelines for noncystic fibrosis bronchiectasis in children and adolescents.Clinical and experimental pediatrics · 2024Article
- Therapeutic Management of Bronchiectasis in Children and Adolescents: A Concise Narrative Review.Journal of clinical medicine · 2024Review
- Cough in Protracted Bacterial Bronchitis and Bronchiectasis.Journal of clinical medicine · 2024Article
- Erdosteine in children and adults with bronchiectasis (BETTER trial): study protocol for a multicentre, double-blind, randomised controlled trial.BMJ open respiratory research · 2024Article
- Article
- Safety profile of drugs used in non-cystic fibrosis bronchiectasis: a narrative review.Therapeutic advances in drug safety · 2024Review
- Randomised controlled trial of perinatal vitamin D supplementation to prevent early-onset acute respiratory infections among Australian First Nations children: the 'D-Kids' study protocol.BMJ open respiratory research · 2023Article
- Reducing exacerbations in children and adults with primary ciliary dyskinesia using erdosteine and/or azithromycin therapy (REPEAT trial): study protocol for a multicentre, double-blind, double-dummy, 2×2 partial factorial, randomised controlled trial.BMJ open respiratory research · 2022Article
- Using tea nanoclusters as β-lactamase inhibitors to cure multidrug-resistant bacterial pneumonia: A promising therapeutic strategy by Chinese materioherbology.Fundamental research · 2022Article
- Monitoring disease progression in childhood bronchiectasis.Frontiers in pediatrics · 2022Review
- Utility of a personalisedBMJ open · 2021Article
- Burden of Care for Children with Bronchiectasis from Parents/Carers Perspective.Journal of clinical medicine · 2021Article
- Synthesis, biological activities and docking studies of pleuromutilin derivatives with piperazinyl urea linkage.Journal of enzyme inhibition and medicinal chemistry · 2021Article
Corrections and comments
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Authors and funding
16 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough amoxicillin-clavulanate is the recommended first-line empirical oral antibiotic treatment for non-severe exacerbations in children with bronchiectasis, azithromycin is also often prescribed for its convenient once-daily dosing. No randomised controlled trials involving acute exacerbations in children with bronchiectasis have been published to our knowledge. We hypothesised that azithromycin is non-inferior to amoxicillin-clavulanate for resolving exacerbations in children with bronchiectasis.
methodsWe did this parallel-group, double-dummy, double-blind, non-inferiority randomised controlled trial in three Australian and one New Zealand hospital between April, 2012, and August, 2016. We enrolled children aged 1-19 years with radiographically proven bronchiectasis unrelated to cystic fibrosis. At the start of an exacerbation, children were randomly assigned to oral suspensions of either amoxicillin-clavulanate (22·5 mg/kg, twice daily) and placebo or azithromycin (5 mg/kg per day) and placebo for 21 days. We used permuted block randomisation (stratified by age, site, and cause) with concealed allocation. The primary outcome was resolution of exacerbation (defined as a return to baseline) by 21 days in the per-protocol population, with a non-inferiority margin of -20%. We assessed several secondary outcomes including duration of exacerbation, time to next exacerbation, laboratory, respiratory, and quality-of-life measurements, and microbiology. This trial was registered with the Australian/New Zealand Registry (ACTRN12612000010897).
findingsWe screened 604 children and enrolled 236. 179 children had an exacerbation and were assigned to treatment: 97 to amoxicillin-clavulanate, 82 to azithromycin). By day 21, 61 (84%) of 73 exacerbations had resolved in the azithromycin group versus 73 (84%) of 87 in the amoxicillin-clavulanate group. The risk difference showed non-inferiority (-0·3%, 95% CI -11·8 to 11·1). Exacerbations were significantly shorter in the amoxicillin-clavulanate group than in the azithromycin group (median 10 days [IQR 6-15] vs 14 days [8-16]; p=0·014). Adverse events were attributed to the trial medication in 17 (21%) of 82 children in the azithromycin group versus 23 (24%) of 97 in the amoxicillin-clavulanate group (relative risk 0·9, 95% CI 0·5 to 1·5).
interpretationBy 21 days of treatment, azithromycin is non-inferior to amoxicillin-clavulanate for resolving exacerbations in children with non-severe bronchiectasis. In some patients, such as those with penicillin hypersensitivity or those likely to have poor adherence, azithromycin provides another option for treating exacerbations, but must be balanced with risk of treatment failure (within a 20% margin), longer exacerbation duration, and the risk of inducing macrolide resistance.
fundingAustralian National Health and Medical Research Council.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.