Esomeprazole to Reduce Organ Failure in Sepsis

Phase 3

Completed

• Conditions: Septic Shock; Sepsis
• Interventions: Drug: Placebo; Drug: Esomeprazole

• Registration Number: NCT03452865
• Lead Sponsor: Università Vita-Salute San Raffaele

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-02-26
• Study First Submitted QC: 2018-02-26
• Study First Posted: 2018-03-02
• Study Start: 2020-01-28
• Primary Completion: 2023-08-21
• Study Completion: 2023-08-21
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-18
• Last Update Posted: 2024-01-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 300

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patients randomized to Placebo Group will receive a bolus of 100 ml of 0.9% sodium chloride for intravenous use administered over 60 minutes with no active principle and an intravenous infusion of 0.9% sodium chloride at a rate of 1.5 ml/hr with no active principle for 72 hours .
Esomeprazole	Esomeprazole	Patients randomized to Esomeprazole Group will receive a bolus of 160 mg of esomeprazole (diluted in 100 ml of 0.9% sodium chloride for intravenous use and administered over 60 minutes) and an intravenous infusion of 12 mg/hr (diluted in 0.9% sodium chloride at a concentration of 8 mg/ml will be injected at a rate of 1.5 ml/hr) for 72 hours .

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Antibiotic-free days	Day 28
Adjusted ICU-free days	Day 28
Mortality	Day 28, 60 and 90
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).

Trial Locations

Locations (17)

Policlinico Univeristario Campus Bio-Medico; 🇮🇹 Roma, Lazio, Italy

IRCCS San Martino Istitute; 🇮🇹 Genova, Liguria, Italy

Humanitas Clinical Institute; 🇮🇹 Rozzano, Lombardy, Italy

Azienda Ospedaliera San Giovanni Battista Molinette di Torino; 🇮🇹 Torino, Italy

Federal Clinical & Research Center for Reanimatology and Rehabilitation; 🇷🇺 Moscow, Russian Federation

Ospedale Santa Maria della Misericordia; 🇮🇹 Udine, Italy

Negovskiy Reanimatology Research Institute; 🇷🇺 Moscow, Russian Federation

Astana Medical University; 🇰🇿 Kazakhstan, Kazakhstan

IRCCS San Raffaele Scientific Institute; 🇮🇹 Milan, MI, Italy

Ospedale Maggiore di Lodi; 🇮🇹 Lodi, Italy

Ospedale di Merano; 🇮🇹 Merano, Italy

A.O.U. Mater Domini; 🇮🇹 Catanzaro, Reggio Calabria, Italy

USSL 10 Veneto; 🇮🇹 San Dona' Di Piave, Venezia, Italy

Università degli Studi della Campania "Luigi Vanvitelli"; 🇮🇹 Napoli, Italy

AOU Pisana; 🇮🇹 Pisa, Italy

A.O.R San Carlo; 🇮🇹 Potenza, Italy

Azienda Ospedaliera Universitaria; 🇮🇹 Cagliari, Sardegna, Italy