Administration of immunotherapy according to the function of immune system in sepsis.
- Conditions
- SepsisMedDRA version: 20.0Level: LLTClassification code 10040053Term: Sepsis secondarySystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2020-005768-74-IT
- Lead Sponsor
- Hellenic Institute for the Study of Sepsis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 280
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.
Patients with signs of fulminant hyper-inflammation or sepsis associated immunoparalysis. 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
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 coagulasenegative 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Secondary end point(s): • 28-day mortality<br>• 90-day mortality<br>• The change of mean total SOFA score on day 15 of the end of treatment<br>• The impact of personalized immunotherapy on the reversal of hyperinflammation 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: day 15, 28 and 90