{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T21:19:57Z","timestamp":1788643197585,"version":"build-2803163510"},"reference-count":40,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T00:00:00Z","timestamp":1627430400000},"content-version":"unspecified","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Haga Teaching Hospital"},{"name":"Stichting Kiddy Goodpills"},{"name":"Elisabeth von Freyburg fonds"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2021,6,2]]},"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Respiratory tract infections (RTIs) affect children all over the world and are associated with significant morbidity and mortality. In particular, recurrent RTIs cause a high burden of disease and lead to frequent doctor visits. Children with recurrent RTIs generally have no significant alterations or deficits in systemic immunity. In an attempt to treat the assumed bacterial component involved, they are often treated with prolonged courses of prophylactic antibiotics taken on a daily basis. Despite its common use, there is no evidence that this is beneficial. Studies assessing the clinical effectiveness of antibiotic prophylaxis as well as potential adverse effects and antibiotic resistance development, are therefore urgently needed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>We present a protocol for a randomised double-blind placebo-controlled trial comparing co-trimoxazole with placebo treatment in children with recurrent RTIs. A total of 158 children (aged 6\u2009months\u201310 years) with recurrent RTIs without significant comorbidity will be enrolled from a minimum of 10 Dutch hospitals. One group receives co-trimoxazole 18\u2009mg\/kg two times per day (36\u2009mg\/kg\/day) and the other group receives a placebo two times per day for a period of 3\u2009months. The main objective is to determine whether antibiotic prophylaxis is more effective than placebo to prevent\/reduce respiratory symptoms in children with recurrent RTIs. Respiratory symptoms will be scored by parents on a daily basis in both study arms by the use of a mobile phone application. Our primary outcome will be the number of days with at least two respiratory symptoms during the treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethics approval was obtained from the Medical Ethics Research Committee Zuidwest Holland\/LDD. A manuscript with the study results will be submitted to a peer-reviewed journal. All participants will be informed about the study results. The results of the study will inform clinical guidelines regarding the prophylactic treatment of children with recurrent RTIs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>NL7044.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2020-044505","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T14:06:38Z","timestamp":1627567598000},"page":"e044505","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Study protocol for a randomised controlled trial evaluating the clinical effect of antibiotic prophylaxis in children with recurrent respiratory tract infections: the Approach study"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3110-9434","authenticated-orcid":false,"given":"Daphne","family":"Peeters","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Haga Hospital, Juliana Childrens Hospital, Den Haag, Zuid-Holland, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"van Geloven","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences, Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loes E","family":"Visser","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy, Haga Teaching Hospital, Den Haag, The Netherlands"},{"name":"Department of Hospital Pharmacy and Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debby","family":"Bogaert","sequence":"additional","affiliation":[{"name":"Center for Inflammation Research, Queen Medical Research Institute, University of Edinburgh, Edinburgh, UK"},{"name":"Department of Paediatric Infectious Diseases and Immunology, University Medical Center Utrecht, Wilhelmina Children\"s Hospital, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie M C","family":"van Rossum","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Erasmus MC Sophia, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertjan J A","family":"Driessen","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Haga Hospital, Juliana Childrens Hospital, Den Haag, Zuid-Holland, The Netherlands"},{"name":"Department of Paediatrics, Maastricht UMC+, Maastricht, The 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