Personalized Immunotherapy in Sepsis (ImmunoSep)
Sepsis
About this trial
This is an interventional treatment trial for Sepsis
Eligibility 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 as defined by ferritin and Quantibrite. 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 novel Coronavirus-2 infection (COVID-19) 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.
Sites / Locations
- Intensive Care Unit, Jena University HospitalRecruiting
- 2nd Department of Critical Care Medicine, ATTIKON University HospitalRecruiting
- Intensive Care Unit, Ioannina University HospitalRecruiting
- Intensive Care Unit, Center for Accident Rehabilitation (KAT) of AthensRecruiting
- Intensive Care Unit, Alexandroupolis University HospitalRecruiting
- 1ST Department of Internal Medicine, Evangelismos General HospitalRecruiting
- 1st Department of Pulmonary Medicine and Intensive Care UnitRecruiting
- 3rd University Department of Internal Medicine, General Hospital of Chest Diseases of Athens SOTIRIARecruiting
- Intensive Care Unit of Center for Respiratory Failure, General Hospital of Chest Diseases of Athens SOTIRIARecruiting
- New Intensive Care Unit, SOTIRIA Athens General Hospital of Chest DiseasesRecruiting
- 4th Department of Internal Medicine, "Attikon" University Hospital, National and Kapodistrian University of Athens, Medical SchoolRecruiting
- Intensive Care Unit, General Hospital ASKLEPIEIO VoulasRecruiting
- 2nd Department of Internal Medicine, Attikon University HospitalRecruiting
- 5th Department of Internal Medicine, Evangelismos General Hospital
- General Oncological Hospital of Kifisia Oi Agioi Anargyroi - Clinic of Intensive Care and Pulmonary Diseases Department of Nursing, University of AthensRecruiting
- Greece Intensive Care Unit General Hospital of Athens KorgialeneioRecruiting
- Intensive Care Unit, "Latsio", Thriasio Elefsis General HospitalRecruiting
- Greece Intensive Care Unit University General Hospital of HeraklionRecruiting
- General Hospital of Karditsa Intensive Care UnitRecruiting
- Intensive Care Unit, "Koutlimbaneio & Triantafylleio" Larissa General HospitalRecruiting
- Department of Internal Medicine, Larissa University HospitalRecruiting
- Intensive Care Unit, TZANEIO Piraeus General HospitalRecruiting
- Intensive Care Unit, Agios Dimitrios General HospitalRecruiting
- Intensive Care Unit, G. Gennimatas General HospitalRecruiting
- Intensive Care Unit, Theageneio Oncological Hospital of ThessalonikiRecruiting
- Intensive Care Unit, Ippokrateion General HospitalRecruiting
- Department of Anesthesiology and Intensive Care Medicine, University General Hospital of Thessaloniki AHEPARecruiting
- Intensive Care Unit, 424 General Military Training HospitalRecruiting
- Department of Internal Medicine and Infectious Diseases, Amsterdam Medical CenterRecruiting
- Intensive Care Unit, University Medical Center RadboudRecruiting
- Infectious Diseases Department, "Iuliu Hatieganu'' University of Medicine and Pharmacy Cluj-NapocaRecruiting
- Intensive Care Unit, Centre Hospitalier Universitaire Vaudois (CHUV)Recruiting
Arms of the Study
Arm 1
Arm 2
Placebo Comparator
Experimental
Standard of care
Immunotherapy
Patients will receive the standard type of treatment decided by the attending physicians. They will also receive 20ml (10ml for patients with creatinine clearance lower than 30ml/min) intravenous (IV) 0.9% saline (N/S) three times daily (every eight hours) for 15 days and 0.5 ml subcutaneous (sc) 1ml 0.9% N/S every other day for a total of 15 days.
Patients will receive the standard type of treatment decided by the attending physicians. They will also receive IV anakinra 200 mg three times daily (every eight hours) or sc rhIFNγ 100 μg once every other day. More precisely, patients randomized for hyper-inflammation will receive anakinra three times daily (every eight hours) for 15 days and sc 0.5 ml N/S 0.9% every other day for 15 days. Patients having immunoparalysis will receive IV 20 ml N/S 0.9% (10ml for patients with creatinine clearance lower than 30ml/min) three times daily (every eight hours) for 15 days and sc rhIFNγ every other day for 15 days. Especially for patients with creatinine clearance lower than 30 ml/min anakinra will be given half dose (i.e. 100 mg three times daily). Creatinine clearance is calculated by the Cockcroft Gault equation [(140-age in years)/ (72 x serum creatinine in mg/dl) for men; this is multiplied by 0.85 for women.