Biomarker-guided immunotherapy vs. standard care in ICU sepsis: A prospective study.

BACKGROUND: This study assessed whether a biomarker-guided approach improves clinical outcomes in septic ICU patients compared to standard care. METHODS: This prospective, biomarker-stratified randomized controlled study was conducted across four ICU treatment units. Adult patients (≥18 years) meeting Sepsis-3 criteria and admitted within 24h of diagnosis were included. Patients were randomly allocated 1:1 to biomarker-guided immunotherapy or standard care using a computer-generated sequence stratified by APACHE II score and symptom duration. The intervention group received immune checkpoint inhibitors, cytokine modulators, or adjuvant immunotherapies according to predefined biomarker profiles. RESULTS: A total of 316 patients were enrolled, with 144 receiving standard care and 172 receiving biomarker-guided immunotherapy. There were no significant differences between groups in age, sex, BMI, or comorbidities. Infection sources and SOFA scores at ICU admission were also comparable. Patients in both groups had comparable APACHE II scores at baseline (median 24 [IQR 22-29] vs. 24 [IQR 19-24], p=0.48) and symptom duration before ICU admission (median 3 days [IQR 2-5] vs. 3 days [IQR 2-4], p=0.096). Admission HLA-DR expression was lower in the biomarker-guided group, and this imbalance was included in adjusted and sensitivity analyses. CONCLUSION: Biomarker-guided immunotherapy led to earlier immune recovery and faster clinical resolution but did not significantly reduce infections or mortality. HLA-DR was a key predictor of infection risk.