Study 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
Pickkers, Peter (Nijmegen)
Angus, Derek C (University of Pittsburgh School of Medicine)
Arend, Jacques (AM-Pharma BV)
Bellomo, Rinaldo (Austin Hospital)
van den Berg, Erik (AM-Pharma BV)
Bernholz, Juliane (AM-Pharma BV)
Bestle, Morten (Copenhagen)
Broglio, Kristine (Berry Consultants)
Carlsen, Jan (AM-Pharma BV)
Doig, Christopher J
Ferrer, Ricard (Universitat Autònoma de Barcelona. Departament d'Infermeria)
Joannidis, Michael (Medical University Innsbruck)
Francois, Bruno (University of Limoges)
Doi, Kent (The University of Tokyo Hospital)
Kellum, John A
Laterre, Pierre-François (Brussels)
Liu, Kathleen (University of California San Fransisco)
Mehta, Ravindra L (University of California)
Murray, Patrick T (Dublin)
Ostermann, Marlies (King's College London)
Pettilä, Ville (Helsinki)
Richards, Sharon (PHASTAR)
Young, Paul (Wellington)
Zarbock, Alexander (Universität Münster)
Kjølbye, Anne Louise (AM-Pharma BV)

Data:	2023
Resum:	Sepsis, 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. ClinicalTrials. gov number: .
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Acute renal failure ; COVID-19 ; Intensive & critical care ; Nephrology
Publicat a:	BMJ open, Vol. 13 (april 2023) , ISSN 2044-6055

DOI: 10.1136/bmjopen-2022-065613
PMID: 37012016

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