{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:21:22Z","timestamp":1790630482294,"version":"4.1.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"PHRC-2017"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Septic shock remains a significant cause of death in critically ill patients. During septic shock, some patients will retain microcirculatory disorders despite optimal hemodynamic support (i.e., fluid resuscitation, vasopressors, inotropes). Alterations in the microcirculation are a key pathophysiological factor of organ dysfunction and death in septic shock patients. Ilomedin is a prostacyclin analog with vasodilatory effect and anti-thrombotic properties (i.e., inhibition of platelet aggregation) preferentially at the microcirculatory level. We hypothesize that early utilization of intravenous Ilomedin in septic shock patients with clinical persistence of microperfusion disorders would improve the recovery of organ dysfunction.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>The I-MICRO trial is a multicenter, prospective, randomized, double-blinded, placebo-controlled study. We plan to recruit 236 adult patients with septic shock and persistent microcirculatory disorders (i.e., skin mottling or increased capillary refill time) despite hemodynamic support. Participants will be randomized to receive a 48-h intravenous infusion of either Ilomedin or placebo starting at the earliest 6\u2009h and later 24\u2009h after septic shock. The primary outcome will be the change (delta) of sequential organ failure assessment (SOFA) score between randomization and day 7. Secondary outcomes will include mean SOFA score during the first 7\u00a0days after randomization, mortality at day 28 post-randomization, number of ventilation-free survival days in the 28\u2009days post-randomization, number of renal replacement therapy-free survival days in the 28\u2009days post-randomization, number of vasopressor-free survival days in the 28\u2009days post-randomization, and mottling score at day 1 after randomization.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Discussion<\/jats:title>\n<jats:p>The trial aims to provide evidence on the efficacy and safety of Ilomedin in patients with septic shock and persistent microcirculatory disorders.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Trial registration<\/jats:title>\n<jats:p>NCT <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03788837\">NCT03788837<\/jats:ext-link>. Registered on 28 December 2018<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13063-020-04549-y","type":"journal-article","created":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T11:45:41Z","timestamp":1593603941000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The I-MICRO trial, Ilomedin for treatment of septic shock with persistent microperfusion defects: a double-blind, randomized controlled trial\u2014study protocol for a randomized controlled trial"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9788-5316","authenticated-orcid":false,"given":"Matthieu","family":"Legrand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hafid Ait","family":"Oufella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"De 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Therefore, patients can be included under the emergency provisions of the law (Article L1122-1-3 of the PHC\/Order N\u00b0 2016-800 of June 16, 2016 - art. 2). Obviously, given the inclusion and non-inclusion criteria, the consent of patients or relatives, if present, cannot be collected at baseline. Thus, given the extreme emergency not allowing collecting the prior consent of the person or relative, the protocol provides that their consent is not necessary. In case of successful resuscitation, delayed consent will be asked to the patient for further participation. The participant shall be informed regarding the study during his or her hospitalization as soon as his or her condition allows. Thereafter, if the patient agrees, he or she signs the delayed consent form to pursue his or her participation in the research, and a \u201cno objection to the use of his\/her data\u201d form for the possible continuation of this research will be completed.According to the law (art. L1122-2 and L1121-8 of the Public Health Code), if the patient has a legal representative (guardian designated by law), it belongs to the patient\u2019s guardian to give his or her consent for further participation to the research and the collection and the exploitation of the data.The study protocol was approved by the institutional review board (IRB) of Sud-Est V on October 30, 2018 (approval number 2018-001709-10) and from the Agence Nationale de S\u00e9curit\u00e9 du Medicament et des Produits de sant\u00e9 (MEDAECNAT-2018-07-00015) and was registered in the clinical trial on December 28, 2018 (NCT03788837) and in EudraCT (N\u00b0 2018-001709-10).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"As a clinical image or other clinical and personal data are not shown, consent for publication is not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"ML reports consulting fees from Novartis, lecture fees from Baxter and Fresenius, and research support from Shingotec.HAO declares no conflict of interestDDB is a consultant to and material for studies by Edwards Lifesciences.ML declares COIs with Amomed (consulting, lecture), Aguettant (consulting), MSD (consulting, lecture), Pfizer (lecture), Aspen (lecture), Orion (lecture), and Octapharma (lecture).BL is a member of an advisory board working for Orion Pharma and has received honoraria from the company for his participation in the board and for giving invited lectures at industry symposia.PR is a co-founder of CardioRenal and declares personal fees (consulting) from Novartis, NovoNordisk, Relypsa, AstraZeneca, Gr\u00fcnenthal, Idorsia, Stealth Peptides, Fresenius, Vifor Fresenius Medical Care Renal Pharma, Vifor, and Clinical Trials Mobile Application, and lecture fees from Bayer and CVRx.EV declares no conflict of interest.FD received lecture fees from Sedana medical, a research grant from the French ministry of health.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"601"}}