A Trial of Validation and Restoration of Immune Dysfunction in Severe Infections and Sepsis (PROVIDE)
Sepsis, Macrophage Activation Syndrome
About this trial
This is an interventional treatment trial for Sepsis focused on measuring sepsis, macrophage activation syndrome, immunoparalysis, anakinra, recombinant human interferon-gamma, HLA-DR
Eligibility 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
Sites / Locations
- 2nd Department of Critical Care Medicine
- 4th Department of Internal Medicine
- Intensive Care Unit, Ioannina University Hospital
- Intensive Care Unit, Center for Accident Rehabilitation (KAT) of Athens
- Department of Internal Medicine, Patras University Hospital
- Intensive Care Unit, Alexandroupolis University Hospital
- 1st Department of Pulmonary Medicine and Intensive Care Unit
- Intensive Care Unit, "Latsio", Thriasio Elefsis General Hospital
- Intensive Care Unit, "Koutlimbaneio & Triantafylleio" Larissa General Hospital
- Department of Internal Medicine, Larissa University Hospital
- Intensive Care Unit, "Tzanio" Piraeus General Hospital
- Intensive Care Unit, "Aghios Dimitrios" Thessaloniki General Hospital
- Intensive Care Unit, "G.Gennimatas" Thessaloniki General Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Placebo Comparator
Experimental
Anakinra
IV Placebo
Recombinant human interferon-gamma
Treatment with iv anakinra 200 mg three times daily (every eight hours) for seven days and sc 1ml N/S 0.9% every other day for 15 days
Treatment with iv 1ml N/S 0.9% three times daily (every eight hours) for seven days and sc 1ml N/S 0.9% every other day for 15 days
Treatment with sc recombinant human interferon-gamma every other day for a total of 15 days and with iv 1ml N/S 0.9% three times daily (every eight hours) for seven days