Sepsis MedDRA version: 20.0 Level: LLT Classification code 10040053 Term: Sepsis secondary System Organ Class: 100000004862
Conditions
Sponsors
Hellenic Institute for the Study of Sepsis
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age equal to or above 18 years. • Both genders. • In case of women, unwillingness to become pregnant during the study period. • Written informed consent provided by the patient or by one first-degree relative/spouse in case of patients unable to consent. • Community-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) or primary bacteremia (BSI). • Sepsis defined by the Sepsis-3 definitions. More precisely, sepsis is defined as the presence of total SOFA (sequential organ failure assessment score) equal to 2 or more for patients who are admitted with infection at the emergency department OR as any increase of admission SOFA by 2 or more points for patients already hospitalized. • Patients with signs of fulminant hyper-inflammation or sepsis-associated immunoparalysis. Since the state of hyper-inflammation is considered more life-threatening than the state of immunoparalysis, patients with lab findings of both immune states are allocated to treatment targeting hyper-inflammation. It is explicitly stated that patients diagnosed with COVID-19 infection may participate only in the fulminant hyper-inflammation arm • Time from classification into sepsis by the Sepsis-3 definitions and start of blind intervention less than 72 hours. 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 180
Exclusion criteria
Exclusion criteria: • Age below 18 years. • Denial for written informed consent. • Acute pyelonephritis or intraabdominal infection, meningitis or skin infection. • Any stage IV malignancy. • Neutropenia defined as an absolute neutrophil count lower than 1,500/mm3. • Any ‘do not resuscitate’ decision in the hospital. • In the case of BSI, patients with blood cultures growing coagulase-negative staphylococci or skin commensals or catheter-related infections cannot be enrolled. • Active tuberculosis (TB) as defined by the co-administration of drugs for the treatment of TB. • Infection by the human immunodeficiency virus (HIV). • Any primary immunodeficiency. • Oral or intravenous intake of corticosteroids at a daily dose equal or greater than 0.4 mg/kg prednisone or greater the last 15 days. • Any anti-cytokine biological treatment the last one month. • Medical history of systemic lupus erythematosus. • Medical history of multiple sclerosis or any other demyelinating disorder. • Pregnancy or lactation. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Our aim is to conduct one RCT in sepsis to assess whether personalized adjunctive immunotherapy directed against a state of either fulminant hyper-inflammation or immunoparalysis is able to change sepsis outcomes. Patients will be selected by a panel of biomarkers and laboratory findings and will be allocated to placebo or immunotherapy treatment according to their needs. The study enrolment will be competitive between the participating study sites.;Secondary Objective: Not applicable;Primary end point(s): The primary efficacy study endpoint will be the comparative difference in the mean total SOFA (Sequential Organ Failure Assessment) score until day 9 after randomization. At least 1.4 points decrease of the mean total SOFA score in the immunotherapy arm compared to the standard-of-care arm on day 9 of follow-up must be achieved. For patients dying before day 9, their mean SOFA score until the day of death will be used for this comparison.;Timepoint(s) of evaluation of this end point: Day 9 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • 28-day mortality • 90-day mortality • The change of mean total SOFA score on day 15 of the end of treatment • The impact of personalized immunotherapy on the reversal of hyper-inflammation or immunoparalysis. This endpoint applies on day 15 of the end of treatment and it is defined as follows: a) for patients with fulminant hyper-inflammation as any at least 15% decrease of the baseline serum ferritin; and b) for patients with sepsis-associated immunoparalysis as restoration of Quantibrite to above 8,000 AB/C with serum ferritin below 4,420 ng/ml;Timepoint(s) of evaluation of this end point: Days 15, 28 and 90 | — |
Countries
Greece, Italy, Netherlands, Switzerland
Contacts
Public ContactPresident of the Board
Hellenic Institute for the Study of Sepsis
Outcome results
None listed