Esomeprazole to Reduce Organ Failure in Sepsis (PPI-SEPSIS)

Università Vita-Salute San Raffaele

Status and phase: Completed; Phase 3

Conditions: Septic Shock; Sepsis

Treatments: Drug: Esomeprazole; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03452865

PPI-SEPSIS

2018-000488-98 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 300 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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300 participants in 2 patient groups, including a placebo group

Esomeprazole

Experimental group

Description:

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 .

Treatment:

Drug: Esomeprazole

Placebo

Placebo Comparator group

Description:

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 .

Treatment:

Drug: Placebo