{Reference Type}: Randomized Controlled Trial
{Title}: Toward personalized immunotherapy in sepsis: The PROVIDE randomized clinical trial.
{Author}: Leventogiannis K;Kyriazopoulou E;Antonakos N;Kotsaki A;Tsangaris I;Markopoulou D;Grondman I;Rovina N;Theodorou V;Antoniadou E;Koutsodimitropoulos I;Dalekos G;Vlachogianni G;Akinosoglou K;Koulouras V;Komnos A;Kontopoulou T;Prekates A;Koutsoukou A;van der Meer JWM;Dimopoulos G;Kyprianou M;Netea MG;Giamarellos-Bourboulis EJ;
{Journal}: Cell Rep Med
{Volume}: 3
{Issue}: 11
{Year}: 11 2022 15
{Factor}: 16.988
{DOI}: 10.1016/j.xcrm.2022.100817
{Abstract}: 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.