Clinical trial NCT03452865: Esomeprazole to Reduce Organ Failure in Sepsis
Official title: Proton Pump Inhibitors (PPI) as a New Strategy for Therapy in Sepsis: Clinical Trial to Reduce Severity of Organ Failure and in Vitro Experiments to Search Specific Hallmarks in Monocytes From Septic Patients and to Characterize the Mechanism of Action of PPI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sepsis
Septic Shock
Keywords: proton pump inhibitor
esomeprazole
sepsis
septic shock
organ failure
SOFA
mortality
Lead sponsor: Università Vita-Salute San Raffaele
Sponsor class: OTHER
Collaborators: name: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
First posted: 2018-03-02
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Sepsis is a severe disease with a high mortality rate and lack of efficacious therapies. Proton pump inhibitors (PPI) are drugs widely used to inhibit acid secretion by gastric cells and with a high safety profile. Carta and Rubartelli (IRCCS San Martino - Genova) have recently reported that PPI, such as esomeprazole, inhibit TNF-alfa and IL-1ß secretion. Moreover, they showed that a single administration of PPI protects mice from endotoxic shock with no adverse effects. PPI-SEPSIS is a randomized, double blind, controlled against placebo clinical trial to test if high-doses esomeprazole in septic patients reduces the severity of organs failure.

In parallel, the investigators will evaluate ex vivo in monocytes from septic patients: redox state and response to inflammatory stimuli; ATP release; metabolic changes and pH; cytokine production; the effects of PPI on these parameters.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old
* Admitted to intensive care unit or emergency department
* Sepsis or septic shock
* Able to express informed consent. For unconscious patients, current laws will be applied as requested by Ethical Committee.

Exclusion Criteria

* Able to express informed consent and deny it
* Known allergy or intolerance to study drug
* Little chance of survival, as defined by a SAPS II score more than 65 point
* Concomitant acquired immunodeficiency syndrome
* On immunosuppressant or long-term corticosteroid therapy
* Receiving lifesaving drugs known to have a strong interference with esomeprazole
* Sepsis or septic shock since over 36 hours
* Severe hepatic dysfunction
* Pregnant or breastfeeding

Primary outcomes:
measure: SOFA score reduction
timeFrame: Days 1-28
Secondary outcomes:
measure: Mortality
timeFrame: Day 28, 60 and 90
measure: Antibiotic-free days
timeFrame: Day 28
measure: Adjusted ICU-free days
timeFrame: Day 28
measure: Single organ failure severity
timeFrame: Days 1-28
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Policlinico Univeristario Campus Bio-Medico
state: Lazio
city: Genova
country: Italy
facility: IRCCS San Martino Istitute
state: Liguria
city: Rozzano
country: Italy
facility: Humanitas Clinical Institute
state: Lombardy
city: Milan
country: Italy
facility: IRCCS San Raffaele Scientific Institute
state: MI
city: Catanzaro
country: Italy
facility: A.O.U. Mater Domini
state: Reggio Calabria
city: Cagliari
country: Italy
facility: Azienda Ospedaliera Universitaria
state: Sardegna
city: San Dona' Di Piave
country: Italy
facility: USSL 10 Veneto
state: Venezia
city: Lodi
country: Italy
facility: Ospedale Maggiore di Lodi
city: Merano
country: Italy
facility: Ospedale di Merano
city: Napoli
country: Italy
facility: Università degli Studi della Campania "Luigi Vanvitelli"
city: Pisa
country: Italy
facility: AOU Pisana
city: Potenza
country: Italy
facility: A.O.R San Carlo
city: Torino
country: Italy
facility: Azienda Ospedaliera San Giovanni Battista Molinette di Torino
city: Udine
country: Italy
facility: Ospedale Santa Maria della Misericordia
city: Kazakhstan
country: Kazakhstan
facility: Astana Medical University
city: Moscow
country: Russian Federation
facility: Federal Clinical & Research Center for Reanimatology and Rehabilitation
city: Moscow
country: Russian Federation
facility: Negovskiy Reanimatology Research Institute
Study officials:
affiliation: Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute
name: Giacomo Monti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Associate Professor of Anesthesiology and Intensive Care, Vita-Salute San Raffaele University
name: Giovanni Landoni, MD
role: STUDY_CHAIR
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citation: Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
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