Table 2 Recent clinical studies that target immunosuppression in sepsis*
From: Targeting the host response in sepsis: current approaches and future evidence
Immune augmentation agent | Mechanism of action | Study population | Primary outcome | Results | Author, year of publication or NCT number |
|---|---|---|---|---|---|
GM-CSF | Increased monocytic HLA-DR expression Increased monocytic production of TLR2/4-induced cytokines | n = 98, septic shock | Difference in the number of patients presenting ≥ 1 ICU-acquired infection at day 28 or ICU discharge | No significant difference; terminated due to insufficient recruitment | Vacheron et al. 2023 [78] |
n = 400, children with sepsis-induced multiple-organ dysfunction syndrome (MODS) | Cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD)-2 score | Recruiting | NCT05266001(GRACE2) | ||
IFNγ | Primary activator of macrophages, neutrophils, and natural killer cells | n = 273, sepsis and septic shock | 28-day mortality | No significant difference | Leventogiannis et al. 2022 [84] |
n = 280, sepsis (< 72 h) | Comparative decrease of the mean total Sequential Organ Failure Assessment (SOFA) score by at least 1.4 points by day 9 from randomization | Recruiting | Kotsaki et al. 2022 NCT04990232 (ImmunoSep) [85] | ||
Thymosin alpha | Stimulates endogenous IFNy secretion and regulates T cell subsets | n = 1106, sepsis | 28-day mortality | Pending | NCT02867267 |
sepsis patients discharged after completing TESTS trial | 3-year mortality | Pending | NCT04901104 | ||
Immunoglobulins (IgM-enriched) | Enhancement of pathogen recognition and clearance, scavenging of toxins and complement, neutralization of inflammatory cytokines | n = 200, sepsis or septic shock | Improvement of the mean multiple-organ failure score on day 7 | Pending | NCT03334006 |
Mesenchymal stem cells (MSC) | Augmentation of bacterial clearance, limitation of apoptosis, injury repair enhancement | n = 9, septic shock | Safety, tolerability | Well tolerated, no infusion-associated, and serious adverse events | McIntyre et al. 2018 [101] |
n = 15, septic shock | Safety, tolerability | Well tolerated, no infusion-associated, and serious adverse events | He et al. 2018 [102] | ||
n = 114, sepsis and septic shock | Reduction in days on mechanical ventilation, or renal replacement therapy, or vasopressors; safety and tolerability | Pending | NCT03369275 (CISS2) | ||
n = 66, septic shock (≥ 2 organ failures other than hemodynamic) | Sofa score on day 7 | Pending | NCT02883803 (CHOCMSC) | ||
n = 21, septic shock | Safety, tolerability | Pending | NCT04961658 (AMETHYST) | ||
Immune checkpoint inhibitor nivolumab | Anti-programmed cell death (PD)-1 monoclonal antibody | n = 13, sepsis | Safety, tolerability, pharmakokinetics | Safe, well tolerated, increase in lymphocyte count and mHLA-DR expression | Watanabe et al. 2020 [114] |
n = 31, sepsis diagnosed ≥ 24 h before treatment, ≥ 1 organ dysfunction, and absolute lymphocyte count ≤ 1.1 × 103 cells/μL | Safety, tolerability and pharmacokinetics over 90d | Safe, no cytokine release syndrome | Hotchkiss et al. 2019 [115] |