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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
300
160 mg of esomeprazole will be diluted in 100 ml of 0.9% sodium chloride for intravenous use for bolus. For continuous intravenous infusion, 40 mg of esomeprazole will be reconstituted by adding 5 ml of 0.9% sodium chloride for intravenous use at a concentration of 8 mg/ml.
0.9% sodium chloride (same ml of the study drug)
Policlinico Univeristario Campus Bio-Medico
Rome, Lazio, Italy
IRCCS San Martino Istitute
Genoa, Liguria, Italy
Humanitas Clinical Institute
Rozzano, Lombardy, Italy
IRCCS San Raffaele Scientific Institute
Milan, MI, Italy
A.O.U. Mater Domini
Catanzaro, Reggio Calabria, Italy
Azienda Ospedaliera Universitaria
Cagliari, Sardinia, Italy
USSL 10 Veneto
San Donà di Piave, Venezia, Italy
Ospedale Maggiore di Lodi
Lodi, Italy
Ospedale di Merano
Merano, Italy
Università degli Studi della Campania "Luigi Vanvitelli"
Napoli, Italy
...and 7 more locations
SOFA score reduction
SOFA (sequential organ failure assessment) score is used to track a person's status during the stay in an intensive care unit to determine the extent of a person's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems which are added up. Each score ranges from 0 to 4. SOFA score ranges from 0 (better outcome) to 24 points (worse outcome).
Time frame: Days 1-28
Mortality
Time frame: Day 28, 60 and 90
Antibiotic-free days
Time frame: Day 28
Adjusted ICU-free days
Time frame: Day 28
Single organ failure severity
Highest mean difference in each different category of SOFA score. SOFA (sequential organ failure assessment) score is used to track a person's status during the stay in an intensive care unit to determine the extent of a person's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems which are added up. Each score ranges from 0 to 4. SOFA score ranges from 0 (better outcome) to 24 points (worse outcome).
Time frame: Days 1-28
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