Cargando…

Adherence-adjusted estimates of benefits and harms from treatment with amoxicillin for LRTI: secondary analysis of a 12-country randomised placebo-controlled trial using randomisation-based efficacy estimators

OBJECTIVES: Estimate the efficacy of amoxicillin for acute uncomplicated lower-respiratory-tract infection (LRTI) in primary care and demonstrate the use of randomisation-based efficacy estimators. DESIGN: Secondary analysis of a two-arm individually-randomised placebo-controlled trial. SETTING: Pri...

Descripción completa

Detalles Bibliográficos
Autores principales: Gillespie, David, Hood, Kerenza, Farewell, Daniel, Butler, Christopher C, Verheij, Theo, Goossens, Herman, Stuart, Beth, Mullee, Mark, Little, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360594/
https://www.ncbi.nlm.nih.gov/pubmed/25748415
http://dx.doi.org/10.1136/bmjopen-2014-006160
_version_ 1782361557388230656
author Gillespie, David
Hood, Kerenza
Farewell, Daniel
Butler, Christopher C
Verheij, Theo
Goossens, Herman
Stuart, Beth
Mullee, Mark
Little, Paul
author_facet Gillespie, David
Hood, Kerenza
Farewell, Daniel
Butler, Christopher C
Verheij, Theo
Goossens, Herman
Stuart, Beth
Mullee, Mark
Little, Paul
author_sort Gillespie, David
collection PubMed
description OBJECTIVES: Estimate the efficacy of amoxicillin for acute uncomplicated lower-respiratory-tract infection (LRTI) in primary care and demonstrate the use of randomisation-based efficacy estimators. DESIGN: Secondary analysis of a two-arm individually-randomised placebo-controlled trial. SETTING: Primary care practices in 12 European countries. PARTICIPANTS: Patients aged 18 or older consulting with an acute LRTI in whom pneumonia was not suspected by the clinician. INTERVENTIONS: Amoxicillin (two 500 mg tablets three times a day for 7 days) or matched placebo. MAIN OUTCOME MEASURES: Clinician-rated symptom severity between days 2–4; new/worsening symptoms and presence of side effects at 4-weeks. Adherence was captured using self-report and tablet counts. RESULTS: 2061 participants were randomised to the amoxicillin or placebo group. On average, 88% of the prescribed amoxicillin was taken. The original analysis demonstrated small increases in both benefits and harms from amoxicillin. Minor improvements in the benefits of amoxicillin were observed when an adjustments for adherence were made (mean difference in symptom severity −0.08, 95% CI −0.17 to 0.01, OR for new/worsening symptoms 0.81, 95% CI 0.66 to 0.98) as well as minor increases in harms (OR for side effects 1.32, 95% CI 1.12 to 1.57). CONCLUSIONS: Adherence to amoxicillin was high, and the findings from the original analysis were robust to non-adherence. Participants consulting to primary care with an acute uncomplicated LRTI can on average expect minor improvements in outcome from taking amoxicillin. However, they are also at an increased risk of experiencing side effects. TRIAL REGISTRATION NUMBERS: Eudract-CT 2007-001586-15 and ISRCTN52261229. The trial was registered at EudraCT in 2007 due to an administrative misunderstanding that EudraCT was a suitable registry—which it was not in 2007, but has become since. On discovery of this error, the trial was also registered at ISRCTN (January 2009). Trial procedures did not change between the two registrations.
format Online
Article
Text
id pubmed-4360594
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BMJ Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-43605942015-03-25 Adherence-adjusted estimates of benefits and harms from treatment with amoxicillin for LRTI: secondary analysis of a 12-country randomised placebo-controlled trial using randomisation-based efficacy estimators Gillespie, David Hood, Kerenza Farewell, Daniel Butler, Christopher C Verheij, Theo Goossens, Herman Stuart, Beth Mullee, Mark Little, Paul BMJ Open Respiratory Medicine OBJECTIVES: Estimate the efficacy of amoxicillin for acute uncomplicated lower-respiratory-tract infection (LRTI) in primary care and demonstrate the use of randomisation-based efficacy estimators. DESIGN: Secondary analysis of a two-arm individually-randomised placebo-controlled trial. SETTING: Primary care practices in 12 European countries. PARTICIPANTS: Patients aged 18 or older consulting with an acute LRTI in whom pneumonia was not suspected by the clinician. INTERVENTIONS: Amoxicillin (two 500 mg tablets three times a day for 7 days) or matched placebo. MAIN OUTCOME MEASURES: Clinician-rated symptom severity between days 2–4; new/worsening symptoms and presence of side effects at 4-weeks. Adherence was captured using self-report and tablet counts. RESULTS: 2061 participants were randomised to the amoxicillin or placebo group. On average, 88% of the prescribed amoxicillin was taken. The original analysis demonstrated small increases in both benefits and harms from amoxicillin. Minor improvements in the benefits of amoxicillin were observed when an adjustments for adherence were made (mean difference in symptom severity −0.08, 95% CI −0.17 to 0.01, OR for new/worsening symptoms 0.81, 95% CI 0.66 to 0.98) as well as minor increases in harms (OR for side effects 1.32, 95% CI 1.12 to 1.57). CONCLUSIONS: Adherence to amoxicillin was high, and the findings from the original analysis were robust to non-adherence. Participants consulting to primary care with an acute uncomplicated LRTI can on average expect minor improvements in outcome from taking amoxicillin. However, they are also at an increased risk of experiencing side effects. TRIAL REGISTRATION NUMBERS: Eudract-CT 2007-001586-15 and ISRCTN52261229. The trial was registered at EudraCT in 2007 due to an administrative misunderstanding that EudraCT was a suitable registry—which it was not in 2007, but has become since. On discovery of this error, the trial was also registered at ISRCTN (January 2009). Trial procedures did not change between the two registrations. BMJ Publishing Group 2015-03-06 /pmc/articles/PMC4360594/ /pubmed/25748415 http://dx.doi.org/10.1136/bmjopen-2014-006160 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Respiratory Medicine
Gillespie, David
Hood, Kerenza
Farewell, Daniel
Butler, Christopher C
Verheij, Theo
Goossens, Herman
Stuart, Beth
Mullee, Mark
Little, Paul
Adherence-adjusted estimates of benefits and harms from treatment with amoxicillin for LRTI: secondary analysis of a 12-country randomised placebo-controlled trial using randomisation-based efficacy estimators
title Adherence-adjusted estimates of benefits and harms from treatment with amoxicillin for LRTI: secondary analysis of a 12-country randomised placebo-controlled trial using randomisation-based efficacy estimators
title_full Adherence-adjusted estimates of benefits and harms from treatment with amoxicillin for LRTI: secondary analysis of a 12-country randomised placebo-controlled trial using randomisation-based efficacy estimators
title_fullStr Adherence-adjusted estimates of benefits and harms from treatment with amoxicillin for LRTI: secondary analysis of a 12-country randomised placebo-controlled trial using randomisation-based efficacy estimators
title_full_unstemmed Adherence-adjusted estimates of benefits and harms from treatment with amoxicillin for LRTI: secondary analysis of a 12-country randomised placebo-controlled trial using randomisation-based efficacy estimators
title_short Adherence-adjusted estimates of benefits and harms from treatment with amoxicillin for LRTI: secondary analysis of a 12-country randomised placebo-controlled trial using randomisation-based efficacy estimators
title_sort adherence-adjusted estimates of benefits and harms from treatment with amoxicillin for lrti: secondary analysis of a 12-country randomised placebo-controlled trial using randomisation-based efficacy estimators
topic Respiratory Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360594/
https://www.ncbi.nlm.nih.gov/pubmed/25748415
http://dx.doi.org/10.1136/bmjopen-2014-006160
work_keys_str_mv AT gillespiedavid adherenceadjustedestimatesofbenefitsandharmsfromtreatmentwithamoxicillinforlrtisecondaryanalysisofa12countryrandomisedplacebocontrolledtrialusingrandomisationbasedefficacyestimators
AT hoodkerenza adherenceadjustedestimatesofbenefitsandharmsfromtreatmentwithamoxicillinforlrtisecondaryanalysisofa12countryrandomisedplacebocontrolledtrialusingrandomisationbasedefficacyestimators
AT farewelldaniel adherenceadjustedestimatesofbenefitsandharmsfromtreatmentwithamoxicillinforlrtisecondaryanalysisofa12countryrandomisedplacebocontrolledtrialusingrandomisationbasedefficacyestimators
AT butlerchristopherc adherenceadjustedestimatesofbenefitsandharmsfromtreatmentwithamoxicillinforlrtisecondaryanalysisofa12countryrandomisedplacebocontrolledtrialusingrandomisationbasedefficacyestimators
AT verheijtheo adherenceadjustedestimatesofbenefitsandharmsfromtreatmentwithamoxicillinforlrtisecondaryanalysisofa12countryrandomisedplacebocontrolledtrialusingrandomisationbasedefficacyestimators
AT goossensherman adherenceadjustedestimatesofbenefitsandharmsfromtreatmentwithamoxicillinforlrtisecondaryanalysisofa12countryrandomisedplacebocontrolledtrialusingrandomisationbasedefficacyestimators
AT stuartbeth adherenceadjustedestimatesofbenefitsandharmsfromtreatmentwithamoxicillinforlrtisecondaryanalysisofa12countryrandomisedplacebocontrolledtrialusingrandomisationbasedefficacyestimators
AT mulleemark adherenceadjustedestimatesofbenefitsandharmsfromtreatmentwithamoxicillinforlrtisecondaryanalysisofa12countryrandomisedplacebocontrolledtrialusingrandomisationbasedefficacyestimators
AT littlepaul adherenceadjustedestimatesofbenefitsandharmsfromtreatmentwithamoxicillinforlrtisecondaryanalysisofa12countryrandomisedplacebocontrolledtrialusingrandomisationbasedefficacyestimators