{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T06:59:58Z","timestamp":1764053998080,"version":"3.45.0"},"reference-count":35,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["848082002"],"award-info":[{"award-number":["848082002"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The aim of this study (PTX\u2010trial) is to determine the optimal dose of pentoxifylline (PTX) in preterm neonates (gestational age &lt; 30\u2009weeks) with (suspected) late onset sepsis (LONS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The PTX\u2010trial is a prospective multicentre open\u2010label sequential dose\u2010optimization study with an adapted continual reassessment method. An up\u2010and\u2010down dose\u2013response design was used, with dose step\u2010up and step\u2010down titration per three patients with a PTX dose of 30\u2009mg\/kg\/day in 6\u2009h for 3\u2009days in the first group. The primary outcome was an ED75, which was defined as a both clinical and chemical effective dose for 75% of preterm neonates with LONS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, 30 neonates were included in the study. As an effective dose was only observed in 27% of the patients, the ED75 could not be determined. There were no significant differences in biochemical and clinical response between the different dosage groups. The largest decrease in nSOFA score after start of PTX was observed in the dosage group of 30\u2009mg\/kg\/day in 6\u2009h.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this dose\u2010finding trial for PTX in preterm neonates, our findings reveal no discernible clinical advantage associated with either increasing or decreasing the PTX dosage. The relatively high variability in sepsis severity and patients' post\u2010natal ages increase the uncertainty of our findings, but the standardly used dosage of 30\u2009mg\/kg\/day (5\u2009mg\/kg\/h for 6\u2009h) has consistently demonstrated safe tolerability without any reported severe adverse events.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70334","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T06:56:15Z","timestamp":1764053775000},"source":"Crossref","is-referenced-by-count":0,"title":["Pentoxifylline dose finding trial in preterm neonates with suspected late onset sepsis (PTX\u2010trial)"],"prefix":"10.1002","author":[{"given":"Serife","family":"Kurul","sequence":"first","affiliation":[{"name":"Department of Neonatal and Paediatric Intensive Care, Division of Neonatology Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. Rob","family":"Taal","sequence":"additional","affiliation":[{"name":"Department of Neonatal and Paediatric Intensive Care, Division of Neonatology Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Mazela","sequence":"additional","affiliation":[{"name":"Department of Neonatology Poznan University of Medical Sciences  Pozna\u0144 Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryszard","family":"Lauterbach","sequence":"additional","affiliation":[{"name":"Department of Neonatology Jagiellonian University Medical College  Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irwin K. M.","family":"Reiss","sequence":"additional","affiliation":[{"name":"Department of Neonatal and Paediatric Intensive Care, Division of Neonatology Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9921-5105","authenticated-orcid":false,"given":"Karel","family":"Allegaert","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy Erasmus University Medical Center  Rotterdam The Netherlands"},{"name":"Department of Development and Regeneration KU Leuven  Leuven Belgium"},{"name":"Department of Pharmaceutical and Pharmacological Sciences KU Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3658-594X","authenticated-orcid":false,"given":"Robert B.","family":"Flint","sequence":"additional","affiliation":[{"name":"Department of Neonatal and Paediatric Intensive Care, Division of Neonatology Erasmus University Medical Center  Rotterdam The Netherlands"},{"name":"Department of Hospital Pharmacy Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sinno H. 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