{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T07:41:35Z","timestamp":1793173295564,"version":"4.5.0"},"reference-count":27,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"unspecified","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"N\u00eemes University Hospital, France"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,12,4]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Sepsis-associated acute kidney injury is common in intensive care and is linked to high morbidity and mortality, yet no specific therapy exists beyond supportive care. Excess circulating labile iron contributes to oxidative stress, mitochondrial dysfunction and cell death via ferroptosis. We hypothesise that targeted removal of labile iron during dialysis may reduce this pathogenic process. This study will evaluate the performance and safety of adding a novel iron chelator named MEX-CD1 (Metal EXtraction - Chitosan DOTAGA 1) to dialysate during continuous veno-venous haemodialysis (CVVHD) in critically ill patients with sepsis-associated acute kidney injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a single-centre, randomised, open-label, crossover phase I\u2013II pilot study in the intensive care unit of N\u00eemes University Hospital, France. 14 adult patients with sepsis-associated acute kidney injury requiring renal replacement therapy will receive two consecutive 24-hour CVVHD sessions: one with standard dialysate and one with dialysate supplemented with MEX-CD1 at 50\u202fmg\/L. Each patient serves as their own control. The primary outcome is the iron concentration in the effluent to measure iron removal performance. Secondary outcomes include plasma iron clearance, trace element loss, biomarkers of oxidative stress and inflammation, and safety outcomes monitored up to 28 days. Statistical analyses will use paired tests and mixed linear regression models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval has been obtained from the Comit\u00e9 de Protection des Personnes (no. 25.01220.000448) and the French National Agency for Safety of Drugs and Medical Devices (no. 2024-A01530-47). Results will be disseminated through peer-reviewed publications and conference presentations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT07236463\">NCT07236463<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-109783","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T11:05:33Z","timestamp":1766487933000},"page":"e109783","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of the performance and safety of adding the iron chelator MEX-CD1 to dialysate during continuous veno-venous haemodialysis for removing excess labile iron in intensive care patients with sepsis-associated acute kidney injury - the Iron in Intensive Care trial (\n                    <i>IRON-I.C<\/i>\n                    .): protocol for a phase I\u2013II randomised crossover pilot study"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct07236463","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct07236463","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7181-8585","authenticated-orcid":false,"given":"Aymeric","family":"Couturier","sequence":"first","affiliation":[{"name":"Department of Nephrology, American Hospital of Paris, Neuilly-sur-Seine, France"},{"name":"Pulmonary and Cardiovascular Aggression in Sepsis APCSe, UPSP 2021.A101, VetAgro Sup, Campus V\u00e9t\u00e9rinaire de Lyon, Universit\u00e9 de Lyon, Marcy L\u2019Etoile, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6074-8577","authenticated-orcid":false,"given":"Chris","family":"Serrand","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology, Public Health and Innovation in Methodology, University of Montpellier, N\u00eemes University Hospital, Nimes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8502-4120","authenticated-orcid":false,"given":"Christophe","family":"Masseguin","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology, Public Health and Innovation in Methodology, University of Montpellier, N\u00eemes University Hospital, Nimes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Allaouchiche","sequence":"additional","affiliation":[{"name":"Critical Care, Hospices Civils de Lyon, Pierre-B\u00e9nite, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Tillement","sequence":"additional","affiliation":[{"name":"Institute Light and Mater, UMR5306, Lyon1 University-CNRS, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Yves","family":"Lefrant","sequence":"additional","affiliation":[{"name":"Research Unit UR\u2011UM103 IMAGINE, University of Montpellier, Department of Anesthesia, Critical Care, Pain Medicine, and Emergency Medicine, N\u00eemes University Hospital, Nimes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5089-8088","authenticated-orcid":false,"given":"Saber Davide","family":"Barbar","sequence":"additional","affiliation":[{"name":"Research Unit UR\u2011UM103 IMAGINE, University of Montpellier, Department of Anesthesia, Critical Care, Pain Medicine, and Emergency Medicine, N\u00eemes University Hospital, Nimes, France"},{"name":"Intensive Care Unit, Department of Anesthesia, Critical Care, Pain Medicine, and Emergency Medicine, University Hospital Centre N\u00eemes Division of Anaesthesiology Intensive Care Pain Medicine and Emergencies, Nimes, Occitanie, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"2026010703474814000_15.12.e109783.1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-015-3934-7"},{"key":"2026010703474814000_15.12.e109783.2","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1007\/s00134-023-07138-0","article-title":"Sepsis-associated acute kidney injury in the intensive care unit: incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes. 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