High dose esomeprazole as an anti-inflammatory agent in sepsis: Protocol for a randomized controlled trial
Monti G. Konkayev A. Carta S. Bradic N. Bruni A. Kotani Y. Guarracino F. Redkin I. Biondi-Zoccai G. Benedetto U. DAscenzo F. Garofalo E. Baiardo Redaelli M. Brizzi G. Forfori F. Borghi G. Scapol S. Momesso E. Cuffaro R. Boffa N. Rauch S. DAmico F. Montrucchio G. Pace M.C. Galbiati C. Bosso S. Savelli F. Giardina G. Silvetti S. Tripodi V.F. Labanca R. Lembo R. Marmiere M. Marzaroli M. Nakhnoukh C. Valsecchi D. Finco G. Agrò F.E. Bove T. Corradi F. Longhini F. Landoni G. Bellomo R. Zangrillo A. Cianfanelli L. Colombo S. Moizo E. Mucci M. Nuzzi M. Oreggia D. Oriani A. Panozzo G. Pasculli N. Plumari V. Salaris D. Sordoni S. Turi S. Rubartelli A. Sitia R. Corea A. Neri G. Baldassarri R. Villano M. Taddei E. Isirdi A. Meroi F. Orso D. Toffoletto F. De Cesaris E. Leggieri C. Seraglio P.M.E. Likhvantsev V. Mattei A. Schiavoni L. Votta C.D. Greco M. Yeltayeva A. Baiocchi M. Bono G. Boraso S. Cabrini L. Cairo M. Cortegiani A. De Pascale G. Pasin L. Pinelli F. Pota V. Sardo S. Sergi M. Usai B. De Sio A.
October 2023Elsevier Inc.
Contemporary Clinical Trials
2023#133
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.
Critical care , Esomeprazole , Intensive care unit , Mortality , Proton pump inhibitors , Sepsis , Septic shock , SOFA score
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IRCCS San Raffaele Scientific Institute, Milan, Italy
Vita-Salute San Raffaele University, Milan, Italy
Astana Medical University, National Scientific Center of Traumatology and Orthopedia, Astana, Kazakhstan
IRCCS Ospedale Policlinico San Martino, Genova, Italy
University Hospital Dubrava, Zagreb, Croatia
University North, Varazdin, Croatia
Anesthesia and Intensive Care, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
Kameda Medical Center, Kamogawa, Japan
Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
Federal Research and Clinical Center of Reanimatology and Rehabilitology, Moscow, Russian Federation
Sapienza University of Rome, Latina, Italy
Mediterranea Cardiocentro, Napoli, Italy
University of G. dAnnunzio Chieti and Pescara, Chieti, Italy
University of Turin, Turin, Italy
Città Della Salute e Della Scienza Hospital, Turin, Italy
University of Pisa, Pisa, Italy
Department of Medicine (DAME), University of Udine, Udine, Italy
Ospedale San Donà di Piave, San Donà di Piave (VE), Italy
Merano Hospital, Merano, Italy
Università della Campania “L. Vanvitelli” Napoli, Napoli, Italy
Ospedale Cardinal Massaia Asti, Asti, Italy
Ospedale “degli Infermi” Di Faenza, Faenza (RA), Italy
University of Messina, Messina, Italy
University of Cagliari, Cagliari, Italy
Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
University of Udine, Udine, Italy
The University of Melbourne, Melbourne, Australia
Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia
Visiting Scientist Division of Genetics and Cell Biology, Vita-Salute San Raffaele University, Milan, Italy
Division of Genetics and Cell Biology, Vita-Salute San Raffaele University, Milan, Italy
Magna Graecia University, Catanzaro, Italy
Department of Anesthesia and Intensive Care Medicine, ASUFC University Hospital of Udine, Udine, Italy
Ospedale San Donà di Piave, San Donà di Piave (VE), Italy
Città della Salute e della Scienza Hospital, Turin, Italy
Merano Hospital, Merano, Italy
ASST of Lodi, Lodi Hospital, Lodi (LO), Italy
Humanitas University, Milan, Italy
IRCCS Humanitas Research Hospital, Milan, Italy
Astana Medical University, National Scientific Center of Traumatology and Orthopedia, Astana, Kazakhstan
IRCSS Policlinico S.Orsola, Università degli Studi di Bologna, Italy
Grande Ospedale Metropolitano “Bianchi-Melacrino-Morelli”, Reggio Calabria, Italy
Ospedale dellAngelo Mestre, Venezia, Italy
Università degli Studi dellInsubria, Varese, Italy
Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi di Varese, Varese, Italy
IRCCS San Gerardo dei Tintori, Monza (MB), Italy
University of Palermo, Palermo, Italy
University Hospital Policlinico Paolo Giaccone, Palermo, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Università Cattolica del Sacro Cuore, Rome, Italy
Azienda Ospedale-Università di Padova, Padova, Italy
AOU Careggi, Firenze, Italy
Istituto Oncologico Veneto- IRCCS, Castelfranco Veneto, Italy
ARNAS Brotzu Cagliari, Cagliari, Italy
Pineta Grande Hospital, Castel Volturno (CE), Italy
IRCCS San Raffaele Scientific Institute
Vita-Salute San Raffaele University
Astana Medical University
IRCCS Ospedale Policlinico San Martino
University Hospital Dubrava
University North
Anesthesia and Intensive Care
Kameda Medical Center
Azienda Ospedaliero Universitaria Pisana
Federal Research and Clinical Center of Reanimatology and Rehabilitology
Sapienza University of Rome
Mediterranea Cardiocentro
University of G. dAnnunzio Chieti and Pescara
University of Turin
Città Della Salute e Della Scienza Hospital
University of Pisa
Department of Medicine (DAME)
Ospedale San Donà di Piave
Merano Hospital
Università della Campania “L. Vanvitelli” Napoli
Ospedale Cardinal Massaia Asti
Ospedale “degli Infermi” Di Faenza
University of Messina
University of Cagliari
Fondazione Policlinico Universitario Campus Bio-Medico
University of Udine
The University of Melbourne
Australian and New Zealand Intensive Care Research Centre
Visiting Scientist Division of Genetics and Cell Biology
Division of Genetics and Cell Biology
Magna Graecia University
Department of Anesthesia and Intensive Care Medicine
Ospedale San Donà di Piave
Città della Salute e della Scienza Hospital
Merano Hospital
ASST of Lodi
Humanitas University
IRCCS Humanitas Research Hospital
Astana Medical University
IRCSS Policlinico S.Orsola
Grande Ospedale Metropolitano “Bianchi-Melacrino-Morelli”
Ospedale dellAngelo Mestre
Università degli Studi dellInsubria
Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi di Varese
IRCCS San Gerardo dei Tintori
University of Palermo
University Hospital Policlinico Paolo Giaccone
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Università Cattolica del Sacro Cuore
Azienda Ospedale-Università di Padova
AOU Careggi
Istituto Oncologico Veneto- IRCCS
ARNAS Brotzu Cagliari
Pineta Grande Hospital
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