{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:15:33Z","timestamp":1790129733684,"version":"4.0.1"},"reference-count":23,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20337270"],"award-info":[{"award-number":["20337270"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>This is a protocol for PPROM-AZM Study, phase II, nonblinded, randomized controlled trial. Bronchopulmonary dysplasia (BPD) at a postmenstrual age of 36 weeks (BPD<jats:sub>36<\/jats:sub>) is often observed in infants with preterm premature rupture of the membranes (pPROM). A regimen of ampicillin (ABPC) intravenous infusion for 2 days and subsequent amoxicillin (AMPC) oral administration for 5 days plus erythromycin (EM) intravenous infusion for 2 days followed by EM oral administration for 5 days is standard treatment for pPROM. However, the effect on the prevention of moderate\/severe BPD<jats:sub>36<\/jats:sub> using the standard treatment has not been confirmed. Recently, it is reported that ampicillin\/sulbactam (ABPC\/SBT) plus azithromycin (AZM) was effective for the prevention of moderate\/severe BPD<jats:sub>36<\/jats:sub> in pPROM patients with amniotic infection of <jats:italic>Ureaplasma<\/jats:italic> species. Therefore, our aim is to evaluate the occurrence rate of the composite outcome of \u201cincidence rate of either moderate\/severe BPD<jats:sub>36<\/jats:sub> or intrauterine fetal death, and infantile death at or less than 36 weeks 0 days\u201d comparing subjects to receive ABPC\/SBT for 14 days plus AZM for 14 days (intervention group) and those to receive ABPC\/SBT for 14 days plus EM for 14 days (control group), in a total of 100 subjects (women with pPROM occurring at 22\u201327 weeks of gestation) in Japan. The recruit of subjects was started on April 2022, and collection in on-going. We also investigate the association between the detection of <jats:italic>Ureaplasma<\/jats:italic> species and occurrence of BPD<jats:sub>36<\/jats:sub>. In addition, information on any adverse events for the mother and fetus and serious adverse events for infants are collected during the observation period. We allocate patients at a rate of 1:1 considering two stratification factors: onset of pPROM (22\u201323 or 24\u201327 weeks) and presence\/absence of a hospital policy for early neonatal administration of caffeine.<\/jats:p>\n<jats:p><jats:bold>Trial registration:<\/jats:bold> The trial number in the Japan Registry of Clinical Trials is <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/ctri.nic.in\/Clinicaltrials\/login.php\/jRCTs031210631\" xlink:type=\"simple\">jRCTs031210631<\/jats:ext-link>.<\/jats:p>","DOI":"10.1371\/journal.pone.0304705","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T18:30:10Z","timestamp":1720549810000},"page":"e0304705","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["A phase II, multicenter, nonblinded, randomized controlled trial for evaluating protective effects of ABPC\/SBT plus, azithromycin versus erythromycin, in pregnant women with pPROM occurring at &lt;28 weeks of gestation on the development of BPD in neonates: Study protocol"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8861-1572","authenticated-orcid":true,"given":"Akihide","family":"Ohkuchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Okazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9266-7811","authenticated-orcid":true,"given":"Shintaro","family":"Iwamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Sako","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itaru","family":"Yanagihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Nomiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on 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