{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T07:39:43Z","timestamp":1765006783610,"version":"3.46.0"},"reference-count":23,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"unspecified","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["21gk0110057h0001"],"award-info":[{"award-number":["21gk0110057h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2023,3,13]]},"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Patent ductus arteriosus (PDA) causes severe morbidity in premature infants. Although the use of indomethacin is the standard therapy for PDA, it is sometimes not applicable because of its adverse effects, such as renal and platelet dysfunctions. Paracetamol has emerged as an alternative to indomethacin owing to its excellent safety profile in infants. Of the recently reported case series and clinical trials on the use of paracetamol for PDA, there are few reports in Japan on paracetamol use in preterm infants. Furthermore, indications for the use of paracetamol for PDA have not been approved for use in PDA. While the safety of intravenous paracetamol therapy in case series of preterm infants treated for haemodynamically significant PDA (hsPDA) has been reported, studies which were conducted to compare paracetamol to indomethacin are limited. We, therefore, intend to investigate the hypothesis that intravenous administration of paracetamol has superior safety over indomethacin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Multicentre open-label randomised controlled trial for intravenous administration of paracetamol for PDA in preterm infants. The inclusion criteria are (1) hsPDA, (2) gestational age from 24 to 34 weeks and birth weight (BW) from 500 to 2000 g, (3) enrolment between 24 hours and 7 days from birth and (4) obtaining parental consent. The primary outcome is renal dysfunction within 48 hours from the last dose of the study drug. Enrolled patients fulfilling all the inclusion criteria are randomly allocated to either intravenous paracetamol or intravenous indomethacin. This trial requires 110 patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The clinical trial would follow Japan\u2019s Clinical Trials Act. The trial protocol was approved by the Clinical Research Review Board of Saitama Medical University (approval number: 222001). A written informed consent would be obtained from one of the parents. The results are expected to be published in a scientific journal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>jRCTs031220386.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Protocol version<\/jats:title>\n                    <jats:p>31 March 2022, version 1.0.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2022-069314","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T11:38:30Z","timestamp":1679571510000},"page":"e069314","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["iPAPP: study protocol for a multicentre randomised controlled trial comparing safety and efficacy of intravenous paracetamol and indomethacin for the treatment of patent ductus arteriosus in preterm infants"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6137-4477","authenticated-orcid":false,"given":"Fumihiko","family":"Namba","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masakazu","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Saitama Medical University Hospital, Iruma, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun","family":"Sakatani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan"},{"name":"Department of Neonatology, Tokyo Metropolitan Children's Medical, Fuchu, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Motojima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayoko","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Promotion, Clinical Research Center, National Center for Child Health and Development, Setagaya, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayumi","family":"Sako","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Promotion, Clinical Research Center, National Center for Child Health and Development, Setagaya, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunio","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Health Policy, National Center for Child Health and Development, Setagaya, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Mikami","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, Department of Data Science, Clinical Research Center, National Center for Child Health and Development, Setagaya, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kou","family":"Kawada","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriyasu","family":"Fukuoka","sequence":"additional","affiliation":[{"name":"Laboratory of Hospital Pharmacy, School of Pharmacy, Nihon University, Funabashi, Chiba, 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