Clinical trial to reduce the severity of organ dysfunction and in-vitro experiments to identify specific hallmarks in septic patients’ monocytes and to characterize the mechanism of action of PPI (PPI-SEPSIS)

Phase 1

• Conditions: Sepsis is a severe disease with a high mortality rate and lack of efficacious therapies; MedDRA version: 20.0Level: PTClassification code 10040047Term: SepsisSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2018-000488-98-IT
• Lead Sponsor: OSPEDALE SAN RAFFAELE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-07
• Last Update Posted: 11 January 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1.Age = 18 years old
2.Admitted to intensive care unit or emergency department
3.Sepsis or septic shock¿(Sepsis defined as acute change in total SOFA score=2 points consequent to the infection. The baseline SOFA score can be assumed to be zero in patients not known to have preexisting organ dysfunction. Septic shock defined as sepsis plus persisting hypotension requiring vasopressors to maintain MAP =65mmHg and having a serum lactate level >2 mmol/L (18mg/dL) despite adequate volume resuscitation)
4.Able to express informed consent as requested by Ethical Committee

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion Criteria

1.Able to express informed consent and deny it
2.Known allergy or intolerance to study drug
3.Little chance of survival, as defined by a SAPS II score more than 65 point¿
4.Concomitant acquired immunodeficiency syndrome (AIDS, Stage 3 HIV infection according to CDC)
5.On immunosuppressant or long-term corticosteroid therapy (more than 0.5 mg/kg/day of prednisone or equivalent for over 30 days)
6.Receiving lifesaving drugs known to have a strong interference with esomeprazole
7.Sepsis or septic shock since over 36 hours¿
8.Severe hepatic dysfunction
9.Pregnant or breastfeeding

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To ascertain if high dose of esomeprazole safely reduces the incidence and severity of organ dysfunction as compared to placebo in adult patients with sepsis or septic shock, with reference to the mean SOFA score in the two groups;Secondary Objective: Identifying new diagnostic or prognostic markers by analyzing functional traits in monocytes from critically ill patients with sepsis: definition of redox state and intra and extracellular pH, quantification of the levels of secreted ATP and cytokines (TNF, IL-1, HMGB1) at baseline and following in vitro TLR stimulation;<br>Understanding the molecular mechanism(s) underlying the therapeutic effects of PPI in acute sepsis: identification of the changes induced in the above parameters by treatment with esomeprazole vs placebo.<br>;Primary end point(s): Reduction of organ dysfunction measured though SOFA score;Timepoint(s) of evaluation of this end point: During hospital stay

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Death from any cause; Antibiotic-free days; Adjusted ICU-free; Single organ failure severity, evaluated by mean difference in each different category of SOFA score.;Timepoint(s) of evaluation of this end point: During hospital stay at days 30, 90, 180 after randomization