High dose esomeprazole as an anti-inflammatory agent in sepsis: Protocol for a randomized controlled trial.

Autor: Monti G; IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy., Konkayev A; Astana Medical University, National Scientific Center of Traumatology and Orthopedia, Astana, Kazakhstan., Carta S; IRCCS Ospedale Policlinico San Martino, Genova, Italy., Bradic N; University Hospital Dubrava, Zagreb, Croatia; University North, Varazdin, Croatia., Bruni A; Anesthesia and Intensive Care, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy., Kotani Y; IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; Kameda Medical Center, Kamogawa, Japan., Guarracino F; Azienda Ospedaliero Universitaria Pisana, Pisa, Italy., Redkin I; Federal Research and Clinical Center of Reanimatology and Rehabilitology, Moscow, Russia., Biondi-Zoccai G; Sapienza University of Rome, Latina, Italy; Mediterranea Cardiocentro, Napoli, Italy., Benedetto U; University of G. d'Annunzio Chieti and Pescara, Chieti, Italy., D'Ascenzo F; University of Turin, Turin, Italy; Città Della Salute e Della Scienza Hospital, Turin, Italy., Garofalo E; Anesthesia and Intensive Care, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy., Baiardo Redaelli M; IRCCS San Raffaele Scientific Institute, Milan, Italy., Brizzi G; Azienda Ospedaliero Universitaria Pisana, Pisa, Italy., Forfori F; University of Pisa, Pisa, Italy., Borghi G; IRCCS San Raffaele Scientific Institute, Milan, Italy., Scapol S; Department of Medicine (DAME), University of Udine, Udine, Italy., Momesso E; Ospedale San Donà di Piave, San Donà di Piave (VE), Italy., Cuffaro R; IRCCS San Raffaele Scientific Institute, Milan, Italy., Boffa N; Ospedale San Donà di Piave, San Donà di Piave (VE), Italy., Rauch S; Merano Hospital, Merano, Italy., D'Amico F; IRCCS San Raffaele Scientific Institute, Milan, Italy., Montrucchio G; University of Turin, Turin, Italy; Città Della Salute e Della Scienza Hospital, Turin, Italy., Pace MC; Università della Campania 'L. Vanvitelli' Napoli, Napoli, Italy., Galbiati C; IRCCS San Raffaele Scientific Institute, Milan, Italy., Bosso S; Ospedale Cardinal Massaia Asti, Asti, Italy., Savelli F; Ospedale 'degli Infermi' Di Faenza, Faenza (RA), Italy., Giardina G; IRCCS San Raffaele Scientific Institute, Milan, Italy., Silvetti S; IRCCS Ospedale Policlinico San Martino, Genova, Italy., Tripodi VF; University of Messina, Messina, Italy., Labanca R; IRCCS San Raffaele Scientific Institute, Milan, Italy., Lembo R; IRCCS San Raffaele Scientific Institute, Milan, Italy., Marmiere M; IRCCS San Raffaele Scientific Institute, Milan, Italy., Marzaroli M; IRCCS San Raffaele Scientific Institute, Milan, Italy., Nakhnoukh C; IRCCS San Raffaele Scientific Institute, Milan, Italy., Valsecchi D; IRCCS San Raffaele Scientific Institute, Milan, Italy., Finco G; University of Cagliari, Cagliari, Italy., Agrò FE; Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy., Bove T; Department of Medicine (DAME), University of Udine, Udine, Italy; University of Udine, Udine, Italy., Corradi F; University of Pisa, Pisa, Italy., Longhini F; Anesthesia and Intensive Care, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy., Landoni G; IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: landoni.giovanni@hsr.it., Bellomo R; The University of Melbourne, Melbourne, Australia; Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia., Zangrillo A; IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
Jazyk: angličtina
Zdroj: Contemporary clinical trials [Contemp Clin Trials] 2023 Oct; Vol. 133, pp. 107319. Date of Electronic Publication: 2023 Aug 23.
DOI: 10.1016/j.cct.2023.107319
Abstrakt: Background: Sepsis is caused by dysregulated immune responses due to infection and still presents high mortality rate and limited efficacious therapies, apart from antibiotics. Recent evidence suggests that very high dose proton pump inhibitors might regulate major sepsis mediators' secretion by monocytes, which might attenuate excessive host reactions and improve clinical outcomes. This effect is obtained with doses which are approximately 50 times higher than prophylactic esomeprazole single daily administration and 17 times higher than the cumulative dose of a three day prophylaxis. We aim to perform a randomized trial to investigate if high dose esomeprazole reduces organ dysfunction in patients with sepsis or septic shock.
Methods: This study, called PPI-SEPSIS, is a multicenter, randomized, double blind, placebo-controlled clinical trial on critically ill septic patients admitted to the emergency department or intensive care unit. A total of 300 patients will be randomized to receive high dose esomeprazole (80 mg bolus followed by 12 mg/h for 72 h and a second 80 mg bolus 12 h after the first one) or equivolume placebo (sodium chloride 0.9%), with 1:1 allocation. The primary endpoint of the study will be mean daily Sequential Organ Failure Assessment (SOFA) score over 10 days. Secondary outcomes will include antibiotic-free days, single organ failure severity, intensive care unit-free days at day 28, and mortality.
Discussion: This trial aims to test the efficacy of high dose esomeprazole to reduce acute organ dysfunction in patients with septic shock.
Trial Registration: This trial was registered on ClinicalTrials.gov with the trial identification NCT03452865 in March 2018.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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