%0 Randomized Controlled Trial
%T Toward personalized immunotherapy in sepsis: The PROVIDE randomized clinical trial.
%A Leventogiannis K
%A Kyriazopoulou E
%A Antonakos N
%A Kotsaki A
%A Tsangaris I
%A Markopoulou D
%A Grondman I
%A Rovina N
%A Theodorou V
%A Antoniadou E
%A Koutsodimitropoulos I
%A Dalekos G
%A Vlachogianni G
%A Akinosoglou K
%A Koulouras V
%A Komnos A
%A Kontopoulou T
%A Prekates A
%A Koutsoukou A
%A van der Meer JWM
%A Dimopoulos G
%A Kyprianou M
%A Netea MG
%A Giamarellos-Bourboulis EJ
%J Cell Rep Med
%V 3
%N 11
%D 11 2022 15
%M 36384100
%F 16.988
%R 10.1016/j.xcrm.2022.100817
%X The state of immune activation may guide targeted immunotherapy in sepsis. In a double-blind, double-dummy randomized clinical study, 240 patients with sepsis due to lung infection, bacteremia, or acute cholangitis were subjected to measurements of serum ferritin and HLA-DR/CD14. Patients with macrophage activation-like syndrome (MALS) or immunoparalysis were randomized to treatment with anakinra or recombinant interferon-gamma or placebo. Twenty-eight-day mortality was the primary endpoint; sepsis immune classification was the secondary endpoint. Using ferritin >4,420 ng/mL and <5,000 HLA-DR receptors/monocytes as biomarkers, patients were classified into MALS (20.0%), immunoparalysis (42.9%), and intermediate (37.1%). Mortality was 79.1%, 66.9%, and 41.6%, respectively. Survival after 7 days with SOFA score decrease was achieved in 42.9% of patients of the immunotherapy arm and 10.0% of the placebo arm (p = 0.042). Three independent immune classification strata are recognized in sepsis. MALS and immunoparalysis are proposed as stratification for personalized adjuvant immunotherapy. Clinicaltrials.gov registration NCT03332225.