{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:51:17Z","timestamp":1790884277320,"version":"4.1.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["ICI23\/00072"],"award-info":[{"award-number":["ICI23\/00072"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hemodynamic insufficiency occurs when tissue oxygen delivery fails to meet demand. Preterm infants are vulnerable to early circulatory failure after birth, impacting mortality and morbidity. Mean arterial pressure is not a reliable indicator of systemic blood flow. Low superior vena cava (SVC) flow, independent of fetal shunts, has been proposed as a robust biomarker of circulatory impairment in this population. Dobutamine, a selective \u03b21 agonist with minimal effect on systemic vascular resistances, is considered the treatment of choice for this condition. However, information about its optimal dosing, efficacy, safety, and pharmacokinetic\/pharmacodynamic (PK\/PD) profile in preterm infants is limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A multicenter, low-intervention, dose-finding trial will be conducted to establish the minimum effective dose of dobutamine to treat hemodynamic insufficiency, defined as SVC flow&lt;51 mL\/kg\/min, in infants \u226432(+6) weeks of gestation during transitional circulation. Baseline echocardiography will be performed within 72 hours after birth. Single commercial dobutamine solution will be prepared and administered intravenously. Participants will be allocated to a dosage regimen by the study statistician, who will adjust probabilities of success based on therapeutic responses. Allocation will be guided by the dose with posterior probability closest to target (80%). PK\/PD assessment will be done at 60 minutes after start of allocated dose and at 180 min of effective dobutamine dose infusion (that achieving stable SVC flow\u2009&gt;\u200955 mL\/kg\/min). The proportion of patients achieving and maintaining adequate hemodynamic status with dobutamine alone during the first 72 hours (efficacy), side effects, and variables explaining interindividual PK\/PD variability will be explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study aims to define the minimum dose of dobutamine with a relevant PD effect on circulation in infants with hemodynamic insufficiency during transitional circulation. This is the first step towards future randomized clinical trials on efficacy and safety of dobutamine for the proposed indication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>EU Clinical trials register, EU CT 2023-504915-34-00, registered 18 April 2023.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0338307","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T18:28:11Z","timestamp":1766168891000},"page":"e0338307","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dose-finding for dobutamine during transitional circulation in the very preterm infant: The study 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