{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:24:30Z","timestamp":1791897870038,"version":"4.3.4"},"reference-count":101,"publisher":"National Institute for Health and Care Research","issue":"60","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["13\/88\/11"],"award-info":[{"award-number":["13\/88\/11"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"\n Background<\/jats:title>\n Data are limited regarding the optimal dose and duration of amoxicillin treatment for community-acquired pneumonia in children.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To determine the efficacy, safety and impact on antimicrobial resistance of shorter (3-day) and longer (7-day) treatment with amoxicillin at both a lower and a higher dose at hospital discharge in children with uncomplicated community-acquired pneumonia.<\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n A multicentre randomised double-blind 2\u2009\u00d7\u20092 factorial non-inferiority trial in secondary care in the UK and Ireland.<\/jats:p>\n <\/jats:sec>\n \n Setting<\/jats:title>\n Paediatric emergency departments, paediatric assessment\/observation units and inpatient wards.<\/jats:p>\n <\/jats:sec>\n \n Participants<\/jats:title>\n Children aged >\u20096 months, weighing 6\u201324\u2009kg, with a clinical diagnosis of community-acquired pneumonia, in whom treatment with amoxicillin as the sole antibiotic was planned on discharge.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Oral amoxicillin syrup at a dose of 35\u201350\u2009mg\/kg\/day compared with a dose of 70\u201390\u2009mg\/kg\/day, and 3 compared with 7 days\u2019 duration. Children were randomised simultaneously to each of the two factorial arms in a 1\u2009:\u20091 ratio.<\/jats:p>\n <\/jats:sec>\n \n Main outcome measures<\/jats:title>\n The primary outcome was clinically indicated systemic antibacterial treatment prescribed for respiratory tract infection (including community-acquired pneumonia), other than trial medication, up to 28 days after randomisation. Secondary outcomes included severity and duration of parent\/guardian-reported community-acquired pneumonia symptoms, drug-related adverse events (including thrush, skin rashes and diarrhoea), antimicrobial resistance and adherence to trial medication.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 824 children were recruited from 29 hospitals. Ten participants received no trial medication and were excluded. Participants [median age 2.5 (interquartile range 1.6\u20132.7) years; 52% male] were randomised to either 3 (n<\/jats:italic>\u2009=\u2009413) or 7 days (n<\/jats:italic>\u2009=\u2009401) of trial medication at either lower (n<\/jats:italic>\u2009=\u2009410) or higher (n<\/jats:italic>\u2009=\u2009404) doses. There were 51 (12.5%) and 49 (12.5%) primary end points in the 3- and 7-day arms, respectively (difference 0.1%, 90% confidence interval \u20133.8% to 3.9%) and 51 (12.6%) and 49 (12.4%) primary end points in the low- and high-dose arms, respectively (difference 0.2%, 90% confidence interval \u20133.7% to 4.0%), both demonstrating non-inferiority. Resolution of cough was faster in the 7-day arm than in the 3-day arm for cough (10 days vs. 12 days) (p<\/jats:italic>\u2009=\u20090.040), with no difference in time to resolution of other symptoms. The type and frequency of adverse events and rate of colonisation by penicillin-non-susceptible pneumococci were comparable between arms.<\/jats:p>\n <\/jats:sec>\n \n Limitations<\/jats:title>\n End-of-treatment swabs were not taken, and 28-day swabs were collected in only 53% of children. We focused on phenotypic penicillin resistance testing in pneumococci in the nasopharynx, which does not describe the global impact on the microflora. Although 21% of children did not attend the final 28-day visit, we obtained data from general practitioners for the primary end point on all but 3% of children.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Antibiotic retreatment, adverse events and nasopharyngeal colonisation by penicillin-non-susceptible pneumococci were similar with the higher and lower amoxicillin doses and the 3- and 7-day treatments. Time to resolution of cough and sleep disturbance was slightly longer in children taking 3 days\u2019 amoxicillin, but time to resolution of all other symptoms was similar in both arms.<\/jats:p>\n <\/jats:sec>\n \n Future work<\/jats:title>\n Antimicrobial resistance genotypic studies are ongoing, including whole-genome sequencing and shotgun metagenomics, to fully characterise the effect of amoxicillin dose and duration on antimicrobial resistance. The analysis of a randomised substudy comparing parental electronic and paper diary entry is also ongoing.<\/jats:p>\n <\/jats:sec>\n \n Trial registration<\/jats:title>\n Current Controlled Trials ISRCTN76888927, EudraCT 2016-000809-36 and CTA 00316\/0246\/001-0006.<\/jats:p>\n <\/jats:sec>\n \n Funding<\/jats:title>\n This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment<\/jats:italic>; Vol. 25, No. 60. See the NIHR Journals Library website for further project information.<\/jats:p>\n <\/jats:sec>","DOI":"10.3310\/hta25600","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T11:33:36Z","timestamp":1636112016000},"page":"1-72","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Amoxicillin duration and dose for community-acquired pneumonia in children: the CAP-IT factorial non-inferiority RCT"],"prefix":"10.3310","volume":"25","clinical-trial-number":[{"clinical-trial-number":"isrctn76888927","registry":"10.18810\/isrctn","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3265-9486","authenticated-orcid":true,"given":"Sam","family":"Barratt","sequence":"first","affiliation":[{"name":"MRC Clinical Trials Unit, University College London, London, 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