Amoxycillin-Clavulanate Vs Azithromycin for Respiratory Exacerbations of Bronchiectasis in Children: A Multi-Centre Double Blind Non-Inferiority Rct

V. Goyal, K. Grimwood, I. Masters, C. Brynes, J. Marchant, P. Morris, R. Ware, P. Van Aspern, K. O'Grady, P. Torzillo, G. McCallum, A. Champion, H. Buntain, I. Mackay, T. Sloots, J. Ungerer, M. Binks, A. Chang

Research output: Contribution to journalMeeting AbstractResearch

Abstract

Introduction: Based on limited available data, amoxycillin‐clavulanate is the current recommended first‐line empirical oral‐antibiotic treatment for non‐severe bronchiectasis exacerbations in children. Azithromycin is an attractive alternative because of its long half‐life, reduced dosing schedule, and good safety profile in children. We tested our primary hypothesis that oral azithromycin is non‐inferior (within 20% margin) to amoxycillin‐clavulanate at achieving resolution of exacerbation by day‐21 of treatment in children with bronchiectasis.

Methods: We conducted a multicentre, parallel group, double‐dummy, double‐blind placebo‐controlled RCT trial in 4 centres. At the start of an exacerbation, 179 children were randomised to receive either amoxycillin‐clavulanate (22.5 mg/kg bd)/placebo or azithromycin (5mg/kg/day)/placebo for 21‐days. Our primary outcome was resolution of exacerbation (defined as ‘return to baseline') by 21‐days. Study was powered for 90% (α=0.05, 1‐sided) with 20% non‐inferiority margin to detect 80% resolution rate by day‐21. Secondary outcomes were cough‐specific quality of life (PC‐QoL) and duration of exacerbation. Generalised linear model was used to calculate relative differences between groups.

Results:
Baseline characteristics of the 2 groups (amoxycillin‐clavulanate n=97 and azithromycin n=82) were similar. By day‐21, resolution was comparable between groups, relative risk 0.99 95%CI 0.84‐1.17, falling within the a‐priori calculated 20% non‐inferiority margin. Between group differences for duration of exacerbation (2 days 95%CI ‐1.7, 5.3) and PC‐QoL at day‐21 compared to beginning of exacerbation was also within our non‐inferiority margin (0.42, 95%CI ‐0.06, 0.89).

Conclusion: Azithromycin is non‐inferior to amoxicillin‐clavulanate for treating non‐severe exacerbations of bronchiectasis in children. Azithromycin may be preferred to amoxicillin‐clavulanate in selected settings e.g. adherence. However, its use needs to be balanced with risk of treatment failure (within 20% compared to amoxicillin‐clavulanate) and inducing macrolide resistance.
LanguageEnglish
Article numberTO-066
Pages54-54
Number of pages1
JournalRespirology
Volume23
Issue numberS1
DOIs
StatePublished - 14 Mar 2018

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Clavulanic Acid
Azithromycin
Bronchiectasis
Amoxicillin
Placebos
Macrolides
Treatment Failure
Cough
Half-Life
Linear Models
Appointments and Schedules
Quality of Life
Anti-Bacterial Agents
Safety
Therapeutics

Cite this

Goyal, V. ; Grimwood, K. ; Masters, I. ; Brynes, C. ; Marchant, J. ; Morris, P. ; Ware, R. ; Van Aspern, P. ; O'Grady, K. ; Torzillo, P. ; McCallum, G. ; Champion, A. ; Buntain, H. ; Mackay, I. ; Sloots, T. ; Ungerer, J. ; Binks, M. ; Chang, A./ Amoxycillin-Clavulanate Vs Azithromycin for Respiratory Exacerbations of Bronchiectasis in Children : A Multi-Centre Double Blind Non-Inferiority Rct. In: Respirology. 2018 ; Vol. 23, No. S1. pp. 54-54
@article{354d03d2e14b4774a1a5a5bd3b7e3993,
title = "Amoxycillin-Clavulanate Vs Azithromycin for Respiratory Exacerbations of Bronchiectasis in Children: A Multi-Centre Double Blind Non-Inferiority Rct",
abstract = "Introduction: Based on limited available data, amoxycillin‐clavulanate is the current recommended first‐line empirical oral‐antibiotic treatment for non‐severe bronchiectasis exacerbations in children. Azithromycin is an attractive alternative because of its long half‐life, reduced dosing schedule, and good safety profile in children. We tested our primary hypothesis that oral azithromycin is non‐inferior (within 20{\%} margin) to amoxycillin‐clavulanate at achieving resolution of exacerbation by day‐21 of treatment in children with bronchiectasis.Methods: We conducted a multicentre, parallel group, double‐dummy, double‐blind placebo‐controlled RCT trial in 4 centres. At the start of an exacerbation, 179 children were randomised to receive either amoxycillin‐clavulanate (22.5 mg/kg bd)/placebo or azithromycin (5mg/kg/day)/placebo for 21‐days. Our primary outcome was resolution of exacerbation (defined as ‘return to baseline') by 21‐days. Study was powered for 90{\%} (α=0.05, 1‐sided) with 20{\%} non‐inferiority margin to detect 80{\%} resolution rate by day‐21. Secondary outcomes were cough‐specific quality of life (PC‐QoL) and duration of exacerbation. Generalised linear model was used to calculate relative differences between groups.Results: Baseline characteristics of the 2 groups (amoxycillin‐clavulanate n=97 and azithromycin n=82) were similar. By day‐21, resolution was comparable between groups, relative risk 0.99 95{\%}CI 0.84‐1.17, falling within the a‐priori calculated 20{\%} non‐inferiority margin. Between group differences for duration of exacerbation (2 days 95{\%}CI ‐1.7, 5.3) and PC‐QoL at day‐21 compared to beginning of exacerbation was also within our non‐inferiority margin (0.42, 95{\%}CI ‐0.06, 0.89).Conclusion: Azithromycin is non‐inferior to amoxicillin‐clavulanate for treating non‐severe exacerbations of bronchiectasis in children. Azithromycin may be preferred to amoxicillin‐clavulanate in selected settings e.g. adherence. However, its use needs to be balanced with risk of treatment failure (within 20{\%} compared to amoxicillin‐clavulanate) and inducing macrolide resistance.",
keywords = "Respiratory System",
author = "V. Goyal and K. Grimwood and I. Masters and C. Brynes and J. Marchant and P. Morris and R. Ware and {Van Aspern}, P. and K. O'Grady and P. Torzillo and G. McCallum and A. Champion and H. Buntain and I. Mackay and T. Sloots and J. Ungerer and M. Binks and A. Chang",
year = "2018",
month = "3",
day = "14",
doi = "10.1111/resp.13267",
language = "English",
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Goyal, V, Grimwood, K, Masters, I, Brynes, C, Marchant, J, Morris, P, Ware, R, Van Aspern, P, O'Grady, K, Torzillo, P, McCallum, G, Champion, A, Buntain, H, Mackay, I, Sloots, T, Ungerer, J, Binks, M & Chang, A 2018, 'Amoxycillin-Clavulanate Vs Azithromycin for Respiratory Exacerbations of Bronchiectasis in Children: A Multi-Centre Double Blind Non-Inferiority Rct' Respirology, vol. 23, no. S1, TO-066, pp. 54-54. DOI: 10.1111/resp.13267

Amoxycillin-Clavulanate Vs Azithromycin for Respiratory Exacerbations of Bronchiectasis in Children : A Multi-Centre Double Blind Non-Inferiority Rct. / Goyal, V.; Grimwood, K.; Masters, I.; Brynes, C.; Marchant, J.; Morris, P.; Ware, R.; Van Aspern, P.; O'Grady, K.; Torzillo, P.; McCallum, G.; Champion, A.; Buntain, H.; Mackay, I.; Sloots, T.; Ungerer, J.; Binks, M.; Chang, A.

In: Respirology, Vol. 23, No. S1, TO-066, 14.03.2018, p. 54-54.

Research output: Contribution to journalMeeting AbstractResearch

TY - JOUR

T1 - Amoxycillin-Clavulanate Vs Azithromycin for Respiratory Exacerbations of Bronchiectasis in Children

T2 - Respirology

AU - Goyal,V.

AU - Grimwood,K.

AU - Masters,I.

AU - Brynes,C.

AU - Marchant,J.

AU - Morris,P.

AU - Ware,R.

AU - Van Aspern,P.

AU - O'Grady,K.

AU - Torzillo,P.

AU - McCallum,G.

AU - Champion,A.

AU - Buntain,H.

AU - Mackay,I.

AU - Sloots,T.

AU - Ungerer,J.

AU - Binks,M.

AU - Chang,A.

PY - 2018/3/14

Y1 - 2018/3/14

N2 - Introduction: Based on limited available data, amoxycillin‐clavulanate is the current recommended first‐line empirical oral‐antibiotic treatment for non‐severe bronchiectasis exacerbations in children. Azithromycin is an attractive alternative because of its long half‐life, reduced dosing schedule, and good safety profile in children. We tested our primary hypothesis that oral azithromycin is non‐inferior (within 20% margin) to amoxycillin‐clavulanate at achieving resolution of exacerbation by day‐21 of treatment in children with bronchiectasis.Methods: We conducted a multicentre, parallel group, double‐dummy, double‐blind placebo‐controlled RCT trial in 4 centres. At the start of an exacerbation, 179 children were randomised to receive either amoxycillin‐clavulanate (22.5 mg/kg bd)/placebo or azithromycin (5mg/kg/day)/placebo for 21‐days. Our primary outcome was resolution of exacerbation (defined as ‘return to baseline') by 21‐days. Study was powered for 90% (α=0.05, 1‐sided) with 20% non‐inferiority margin to detect 80% resolution rate by day‐21. Secondary outcomes were cough‐specific quality of life (PC‐QoL) and duration of exacerbation. Generalised linear model was used to calculate relative differences between groups.Results: Baseline characteristics of the 2 groups (amoxycillin‐clavulanate n=97 and azithromycin n=82) were similar. By day‐21, resolution was comparable between groups, relative risk 0.99 95%CI 0.84‐1.17, falling within the a‐priori calculated 20% non‐inferiority margin. Between group differences for duration of exacerbation (2 days 95%CI ‐1.7, 5.3) and PC‐QoL at day‐21 compared to beginning of exacerbation was also within our non‐inferiority margin (0.42, 95%CI ‐0.06, 0.89).Conclusion: Azithromycin is non‐inferior to amoxicillin‐clavulanate for treating non‐severe exacerbations of bronchiectasis in children. Azithromycin may be preferred to amoxicillin‐clavulanate in selected settings e.g. adherence. However, its use needs to be balanced with risk of treatment failure (within 20% compared to amoxicillin‐clavulanate) and inducing macrolide resistance.

AB - Introduction: Based on limited available data, amoxycillin‐clavulanate is the current recommended first‐line empirical oral‐antibiotic treatment for non‐severe bronchiectasis exacerbations in children. Azithromycin is an attractive alternative because of its long half‐life, reduced dosing schedule, and good safety profile in children. We tested our primary hypothesis that oral azithromycin is non‐inferior (within 20% margin) to amoxycillin‐clavulanate at achieving resolution of exacerbation by day‐21 of treatment in children with bronchiectasis.Methods: We conducted a multicentre, parallel group, double‐dummy, double‐blind placebo‐controlled RCT trial in 4 centres. At the start of an exacerbation, 179 children were randomised to receive either amoxycillin‐clavulanate (22.5 mg/kg bd)/placebo or azithromycin (5mg/kg/day)/placebo for 21‐days. Our primary outcome was resolution of exacerbation (defined as ‘return to baseline') by 21‐days. Study was powered for 90% (α=0.05, 1‐sided) with 20% non‐inferiority margin to detect 80% resolution rate by day‐21. Secondary outcomes were cough‐specific quality of life (PC‐QoL) and duration of exacerbation. Generalised linear model was used to calculate relative differences between groups.Results: Baseline characteristics of the 2 groups (amoxycillin‐clavulanate n=97 and azithromycin n=82) were similar. By day‐21, resolution was comparable between groups, relative risk 0.99 95%CI 0.84‐1.17, falling within the a‐priori calculated 20% non‐inferiority margin. Between group differences for duration of exacerbation (2 days 95%CI ‐1.7, 5.3) and PC‐QoL at day‐21 compared to beginning of exacerbation was also within our non‐inferiority margin (0.42, 95%CI ‐0.06, 0.89).Conclusion: Azithromycin is non‐inferior to amoxicillin‐clavulanate for treating non‐severe exacerbations of bronchiectasis in children. Azithromycin may be preferred to amoxicillin‐clavulanate in selected settings e.g. adherence. However, its use needs to be balanced with risk of treatment failure (within 20% compared to amoxicillin‐clavulanate) and inducing macrolide resistance.

KW - Respiratory System

U2 - 10.1111/resp.13267

DO - 10.1111/resp.13267

M3 - Meeting Abstract

VL - 23

SP - 54

EP - 54

JO - Respirology

JF - Respirology

SN - 1323-7799

IS - S1

M1 - TO-066

ER -