A Trial of Validation and Restoration of Immune Dysfunction in Severe Infections and Sepsis

• Status: Completed
• Trial end date: 2019-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The aim of the study is to conduct one RCT of personalized immunotherapy in sepsis targeting patients who lie either on the predominantly hyper-inflammatory arm or on the predominantly hypo-inflammatory arm of the spectrum of the host response. These patients will be selected by the use of a panel of biomarkers and laboratory findings and they will be randomly allocated to placebo or immunotherapy treatment according to their needs.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hellenic Institute for the Study of Sepsis
• Treatments: Interferon-gamma; Interferons; Interleukin 1 Receptor Antagonist Protein

Criteria

Inclusion Criteria:

• Age equal to or above 18 years

• Male or female gender

• In case of women, unwillingness to remain 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 or hospital-acquired pneumonia or ventilator-associated pneumonia or primary bacteremia or acute cholangitis

• Sepsis defined by the Sepsis-3 definitions.

• Patients with laboratory diagnosis of MALS or hypo-inflammation (immune-paralysis) based on two consecutive blood sampling with 24 hours apart. MALS is defined as the presence of ferritin >4,420 ng/ml and hypo-inflammation as HLA-DR expression on CD14-monocytes (co-expression) less than 30%

Exclusion Criteria:

• Age below 18 years

• Denial for written informed consent

• Acute pyelonephritis or intraabdominal infection other than AC, meningitis or skin infection. It is explicitly stated that in the case of a patient with both AC and any other type of intraabdominal infection, the patient cannot be enrolled.

• Any stage IV malignancy

• Any do not resuscitate decision

• 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 IV intake of corticosteroids at a daily dose equal or greater than 0.4 mg 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