Study "IMMUNOSEP" PERSONALIZED IMMUNOTHERAPY IN SEPSIS

Germany, Greece, Italy, Netherlands, Switzerland (ICTRP)

ID di studio ICTRP
EUCTR2020-005768-74 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
ImmunoSep (Personalised Immunotherapy in Sepsis) international double-blind, double-dummy, placebo-controlled randomised clinical trial: study protocol (BASEC)

Titolo accademico
PERSONALIZED IMMUNOTHERAPY IN SEPSIS: A MULTICENTRE AND MULTINATIONAL, DOUBLE-BLIND, DOUBLE-DUMMY RANDOMIZED CLINICAL TRIAL (THE IMMUNOSEP TRIAL) - ImmunoSep (ICTRP)

Titolo pubblico
Administration of immunotherapy according to the function of immune system in sepsis (ICTRP)

Malattie studiate
Sepsis
MedDRA version: 20.0Level: LLTClassification code 10040053Term: Sepsis secondarySystem Organ Class: 100000004862;Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01] (ICTRP)

Intervento studiato

Trade Name: Kineret
Product Name: Anakinra
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Anakinra
CAS Number: 143090-92-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Injection
Route of administration of the placebo: Intravenous use

Trade Name: Imukin
Product Name: Recombinant human interferon gamma-1b
Pharmaceutical Form: Solution for injection
INN or Proposed INN: recombinant human interferon gamma-1b
CAS Number: 98059-61-1
Other descriptive name: INTERFERON GAMMA-1B
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.1-
Pharmaceutical form of the placebo: Injection
Route of administration of the placebo: Subcutaneous use

(ICTRP)

Tipo di studio
Interventional clinical trial of medicinal product (ICTRP)

Disegno dello studio
Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2 (ICTRP)

Criteri di inclusione/esclusione
Gender:
Female: yes
Male: yes

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 hyperinflammation 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.
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
(ICTRP)

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 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.


Endpoint primari e secondari
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 (ICTRP)

Secondary end point(s): ? 28-day mortality
? 90-day mortality
? The change of mean total SOFA score on day 15 of the end of treatment.
? 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: Days 15, 28 and 90 (ICTRP)

Data di registrazione
03.02.2022 (ICTRP)

Inclusione del primo partecipante
25.05.2022 (ICTRP)

Sponsor secondari
non disponibile

Contatti aggiuntivi
President of the Board, insepsis@otenet.gr, 00302107480662, Hellenic Institute for the Study of Sepsis (ICTRP)

ID secondari
ImmunoSep, 2020-005768-74-GR (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-005768-74 (ICTRP)