Sepsis, Septic Shock
Conditions
Keywords
proton pump inhibitor, esomeprazole, sepsis, septic shock, organ failure, SOFA, mortality
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.
Interventions
DRUGEsomeprazole
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.
DRUGPlacebo
0.9% sodium chloride (same ml of the study drug)
Sponsors
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Università Vita-Salute San Raffaele
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SOFA score reduction | Days 1-28 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted ICU-free days | Day 28 | — |
| Mortality | Day 28, 60 and 90 | — |
| Antibiotic-free days | Day 28 | — |
| Single organ failure severity | Days 1-28 | 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). |
Countries
Italy, Kazakhstan, Russia
Outcome results
None listed