Multiorgan Failure, Sepsis, Septic Shock
Conditions
Keywords
oXiris, Target Trial Emulation, Extracorporeal Blood Purification
Brief summary
This study aims to evaluate the clinical effectiveness of the oXiris® hemofilter in patients with septic shock and acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). While some studies suggest that oXiris® may improve hemodynamic stability by removing endotoxins and cytokines, its impact on survival remains inconsistent.To provide more reliable causal evidence, this multicenter retrospective cohort study utilizes a Target Trial Emulation (TTE) approach. The study will compare patients treated with the oXiris® filter to those treated with standard CRRT filters, focusing on in-hospital mortality and other clinical outcomes such as fluid balance and vasopressor requirements.
Detailed description
Background: Septic shock is characterized by a dysregulated host response to infection, leading to a "cytokine storm" that causes organ dysfunction and hemodynamic instability. Extracorporeal blood purification (EBP) using the oXiris® filter is designed to restore immune homeostasis by adsorbing both endotoxins and cytokines while performing standard CRRT functions. However, existing observational data often suffer from selection and immortal time biases. Study Design and Methodology: This study employs the Target Trial Emulation (TTE) framework to mimic the design of a randomized controlled trial using retrospective observational data. * Target Population: Adult patients (≥19 years) admitted to the ICU with septic shock and AKI requiring CRRT between March 2021 and August 2025. * Time Zero: Defined as the initiation of CRRT. * Treatment Strategies: Strategy A (oXiris): CRRT initiated with the oXiris® filter. Strategy B (Control): CRRT initiated with a standard filter, sourced from the Korea Sepsis Alliance registry. * Data Sources: Data will be collected from five major medical centers in South Korea: Seoul National University Bundang Hospital, Hallym University Sacred Heart Hospital, Chung-Ang University Hospital, Samsung Medical Center, and Asan Medical Center. * Statistical Analysis Plan: To adjust for baseline confounding and confounding by indication, propensity score-based Inverse Probability of Treatment Weighting (IPTW) will be applied. Primary Outcome: In-hospital mortality will be analyzed using an IPTW-weighted Cox proportional hazards model. Secondary Outcomes: * Fluid Balance: 3-day cumulative fluid balance using landmark analysis and IPTW-weighted linear regression. * Vasopressor Weaning: Analyzed using a weighted Fine-Gray risk model, considering death as a competing risk. * Organ Function & Inflammation: Repeated measures of SOFA scores and inflammatory markers (CRP, Procalcitonin, lactate) using IPTW-weighted linear mixed-effects models. * Renal Recovery: Evaluated via IPTW-weighted logistic regression.
Interventions
None listed
Sponsors
Seoul National University Bundang Hospital
Vantive Health LLC
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults aged 19 years or older. * Admitted to the ICU with septic shock (Sepsis-3 criteria) between March 2021 and August 2025. * Required Continuous Renal Replacement Therapy (CRRT) due to acute kidney injury (AKI).
Exclusion criteria
* Death or withdrawal of life-sustaining therapy within 48 hours of ICU admission. * Patients with End-Stage Renal Disease (ESRD). * Patients with missing critical covariates.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| In-hospital Mortality | From the initiation of CRRT (Time zero) until hospital discharge or death. | The primary objective is to evaluate the causal effect of oXiris® hemofilter use on survival during the hospital stay compared to standard CRRT. Statistical analysis will be performed using an Inverse Probability of Treatment Weighting (IPTW)-weighted Cox proportional hazards model to adjust for baseline and time-varying confounders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 3-day Cumulative Fluid Balance | 3 days after CRRT initiation. | Comparison of the total fluid intake and output over the first 3 days after CRRT initiation. |
| Time to Vasopressor Weaning | From CRRT initiation through ICU discharge, up to 28 days | The duration from CRRT initiation until the successful discontinuation of all vasopressors. |
| Organ Dysfunction Improvement | Baseline (Day 0) and Days 1, 2, 3, 7 of ICU stay. | Evaluation of organ failure improvement through repeated measures of the Sequential Organ Failure Assessment (SOFA) score. |
| Changes in Inflammatory Markers | Baseline (Day 0) and Days 1, 2, 3, 7 of ICU stay. | Assessment of the reduction in serum levels of CRP, Procalcitonin, and lactate. |
| Renal Recovery Status | From CRRT initiation through hospital discharge, up to 90 days | Proportion of patients who recover renal function and do not require renal replacement therapy at the time of hospital discharge. |
Countries
South Korea
Contacts
CONTACTSung Yoon Lim, MD. PhD
CONTACTMyung Jin Song, MD.PhD
PRINCIPAL_INVESTIGATORSung Yoon Lim, MD.PhD
Seoul National University Bundang Hospital
Outcome results
None listed