PERSONALIZED IMMUNOTHERAPY IN SEPSIS: A MULTICENTRE AND MULTINATIONAL, DOUBLE-BLIND, DOUBLE-DUMMY RANDOMIZED CLINICAL TRIA

Phase 2

Recruiting

• Conditions: dysregulated host response to an infection; sepsis; 10004018

• Registration Number: NL-OMON51161
• Lead Sponsor: Hellenic Institute for the Study of Sepsis

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 80

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.

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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The difference in the mean total SOFA (Sequential Organ Failure Assessment)<br /><br>score until day 9 after randomization.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- 28-day mortality<br /><br>- 90-day mortality<br /><br>- The change of mean total SOFA score on day 15 of the end of treatment<br /><br>- The impact of personalized immunotherapy on the reversal of<br /><br>hyper-inflammation or immunoparalysis.<br /><br>- The impact of personalized immunotherapy on the resolution of infection<br /><br>leading to study enrolment.<br /><br>- The development of genomic, epigenomic, proteomic, metabolomic and<br /><br>microbiomic surrogate biomarkers for the primary and secondary endpoints. </p><br>