Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/32655
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dc.contributor.authorPickkers, Peter-
dc.contributor.authorAngus, Derek C-
dc.contributor.authorArend, Jacques-
dc.contributor.authorBellomo, Rinaldo-
dc.contributor.authorvan den Berg, Erik-
dc.contributor.authorBernholz, Juliane-
dc.contributor.authorBestle, Morten-
dc.contributor.authorBroglio, Kristine-
dc.contributor.authorCarlsen, Jan-
dc.contributor.authorDoig, Christopher J-
dc.contributor.authorFerrer, Ricard-
dc.contributor.authorJoannidis, Michael-
dc.contributor.authorFrancois, Bruno-
dc.contributor.authorDoi, Kent-
dc.contributor.authorKellum, John A-
dc.contributor.authorLaterre, Pierre-François-
dc.contributor.authorLiu, Kathleen-
dc.contributor.authorMehta, Ravindra L-
dc.contributor.authorMurray, Patrick T-
dc.contributor.authorOstermann, Marlies-
dc.contributor.authorPettilä, Ville-
dc.contributor.authorRichards, Sharon-
dc.contributor.authorYoung, Paul-
dc.contributor.authorZarbock, Alexander-
dc.contributor.authorKjølbye, Anne Louise-
dc.date2023-04-
dc.date.accessioned2023-04-14T02:47:35Z-
dc.date.available2023-04-14T02:47:35Z-
dc.date.issued2023-04-03-
dc.identifier.citationBMJ Open 2023-04-03; 13(4)en_US
dc.identifier.issn2044-6055-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/32655-
dc.description.abstractSepsis, the leading cause of acute kidney injury (AKI), is associated with a high morbidity and mortality. Alkaline phosphatase (ALP) is an endogenous detoxifying enzyme. A recombinant human ALP compound, ilofotase alfa, showed no safety or tolerability concerns in a phase 2 trial. Renal function improvement over 28 days was significantly greater in the ilofotase alfa group. Moreover, a significant relative reduction in 28-day all-cause mortality of >40% was observed. A follow-up trial has been designed to confirm these findings. This is a phase 3, global, multi-centre, randomised, double-blind, placebo-controlled, sequential design trial in which patients are randomly assigned to either placebo or 1.6 mg/kg ilofotase alfa. Randomisation is stratified by baseline modified Sequential Organ Failure Assessment (mSOFA) score and trial site. The primary objective is to confirm the survival benefit with ilofotase alfa by demonstrating a reduction in 28-day all-cause mortality in patients with sepsis-associated AKI requiring vasopressors. A maximum of 1400 patients will be enrolled at ∼120 sites in Europe, North America, Japan, Australia and New Zealand. Up to four interim analyses will take place. Based on predefined decision rules, the trial may be stopped early for futility or for effectiveness. In addition, patients with COVID-19 disease and patients with 'moderate to severe' chronic kidney disease are analysed as 2 separate cohorts of 100 patients each. An independent Data Monitoring Committee evaluates safety data at prespecified intervals throughout the trial. The trial is approved by relevant institutional review boards/independent ethics committees and is conducted in accordance with the ethical principles of the Declaration of Helsinki, guidelines of Good Clinical Practice, Code of Federal Regulations and all other applicable regulations. Results of this study will determine the potential of ilofotase alfa to reduce mortality in critically ill patients with sepsis-associated AKI and will be published in a peer-reviewed scientific journal. EudraCT CT Number 2019-0046265-24. US IND Number 117 605 Pre-results. gov number: NCT04411472.en_US
dc.language.isoeng-
dc.subjectCOVID-19en_US
dc.subjectacute renal failureen_US
dc.subjectintensive & critical careen_US
dc.subjectnephrologyen_US
dc.titleStudy protocol of a randomised, double-blind, placebo-controlled, two-arm parallel-group, multi-centre phase 3 pivotal trial to investigate the efficacy and safety of recombinant human alkaline phosphatase for treatment of patients with sepsis-associated acute kidney injury.en_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleBMJ Openen_US
dc.identifier.affiliationIntensive Care Medicine, Radboudumc, Nijmegen, The Netherlands peter.en_US
dc.identifier.affiliationDepartment of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.en_US
dc.identifier.affiliationAM-Pharma BV, Bunnik, The Netherlands.en_US
dc.identifier.affiliationDepartment of Critical Care, The University of Melbourne, Melbourne, Victoria, Australia.;en_US
dc.identifier.affiliationIntensive Careen_US
dc.identifier.affiliationDepartment of Anaesthesiology and Intensive care, Nordsjaellands Hospital, Hillerod, Denmark.;Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.en_US
dc.identifier.affiliationBerry Consultants, Austin, Texas, USA.en_US
dc.identifier.affiliationDepartment of Critical Care Medicine, University of Calgary Medical Centre, Calgary, Alberta, Canada.en_US
dc.identifier.affiliationIntensive Care Department, Universitat Autònoma de Barcelona, Barcelona, Spain.en_US
dc.identifier.affiliationDivision of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria.en_US
dc.identifier.affiliationICU and Inserm C1C, University of Limoges, Limoges, France.en_US
dc.identifier.affiliationEmergency and Critical Care Medicine, The University of Tokyo Hospital, Tokyo, Japan.en_US
dc.identifier.affiliationDepartment of Critical Care Medicine, Cliniques Universitaires Saint-Luc, Brussels, Belgium.en_US
dc.identifier.affiliationDivisions of Critical Care Medicine and Nephrology, Departments of Anesthesia and Medicine, University of California San Fransisco, San Francisco, California, USA.en_US
dc.identifier.affiliationDepartment of Medicine, University of California, San Diego, California, USA.en_US
dc.identifier.affiliationSchool of Medicine, University College Dublin, Dublin, Ireland.en_US
dc.identifier.affiliationDepartment of Critical Care, King's College London, Guy's & St Thomas' Hospital, London, UK.en_US
dc.identifier.affiliationDivision of Intensive Care Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, Helsingin Yliopisto Laaketieteellinen tiedekunta, Helsinki, Finland.en_US
dc.identifier.affiliationPHASTAR, London, UK.en_US
dc.identifier.affiliationIntensive Care Unit, Wellington Hospital, Wellington, New Zealand.en_US
dc.identifier.affiliationDepartment of Anesthesiology, Intensive Care and Pain Medicine, Universität Münster, Münster, Germany.en_US
dc.identifier.doi10.1136/bmjopen-2022-065613en_US
dc.type.contentTexten_US
dc.identifier.orcid0000-0002-1104-4303en_US
dc.identifier.orcid0000-0001-8516-1839en_US
dc.identifier.orcid0000-0002-3428-3083en_US
dc.identifier.orcid0000-0002-2124-1714en_US
dc.identifier.pubmedid37012016-
dc.description.volume13-
dc.description.issue4-
dc.description.startpagee065613-
dc.subject.meshtermssecondaryAlkaline Phosphatase/therapeutic use-
dc.subject.meshtermssecondarySepsis/complications-
dc.subject.meshtermssecondarySepsis/drug therapy-
dc.subject.meshtermssecondaryAcute Kidney Injury/etiology-
local.name.researcherBellomo, Rinaldo
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptIntensive Care-
crisitem.author.deptData Analytics Research and Evaluation (DARE) Centre-
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