Metformin for sepsis-associated AKI: a protocol for the Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI).

Autor:	Saraiva IE; CRISMA Center, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.; Program for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Hamahata N; Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Huang DT; CRISMA Center, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.; Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Kane-Gill SL; CRISMA Center, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.; Program for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.; Department of Pharmacy & Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA.; Department of Pharmacy, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA., Rivosecchi RM; Department of Pharmacy, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA., Shiva S; Department of Pharmacology & Chemical Biology, Vascular Medical Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Nolin TD; Department of Pharmacy & Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.; Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Chen X; Department of Biostatistics, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Minturn J; CRISMA Center, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.; Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Chang CH; Department of Biostatistics, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Li X; Department of Pharmacy & Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA., Kellum J; Program for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Gómez H; CRISMA Center, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA gomezh@upmc.edu.; Program for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Jazyk:	angličtina
Zdroj:	BMJ open [BMJ Open] 2024 Apr 30; Vol. 14 (4), pp. e081120. Date of Electronic Publication: 2024 Apr 30.
DOI:	10.1136/bmjopen-2023-081120
Abstrakt:	Introduction: Acute kidney injury (AKI) is a common complication of sepsis associated with increased risk of death. Preclinical data and observational human studies suggest that activation of AMP-activated protein kinase, an ubiquitous master regulator of energy that can limit mitochondrial injury, with metformin may protect against sepsis-associated AKI (SA-AKI) and mortality. The Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI) aims to evaluate the safety and feasibility of enteral metformin in patients with sepsis at risk of developing SA-AKI. Methods and Analysis: Blind, randomised, placebo-controlled clinical trial in a single-centre, quaternary teaching hospital in the USA. We will enrol adult patients (18 years of age or older) within 48 hours of meeting Sepsis-3 criteria, admitted to intensive care unit, with oral or enteral access. Patients will be randomised 1:1:1 to low-dose metformin (500 mg two times per day), high-dose metformin (1000 mg two times per day) or placebo for 5 days. Primary safety outcome will be the proportion of metformin-associated serious adverse events. Feasibility assessment will be based on acceptability by patients and clinicians, and by enrolment rate. Ethics and Dissemination: This study has been approved by the Institutional Review Board. All patients or surrogates will provide written consent prior to enrolment and any study intervention. Metformin is a widely available, inexpensive medication with a long track record for safety, which if effective would be accessible and easy to deploy. We describe the study methods using the Standard Protocol Items for Randomized Trials framework and discuss key design features and methodological decisions. LiMiT AKI will investigate the feasibility and safety of metformin in critically ill patients with sepsis at risk of SA-AKI, in preparation for a future large-scale efficacy study. Main results will be published as soon as available after final analysis. Trial Registration Number: NCT05900284. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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