Effect of oXiris Hemofilter Use in Septic Shock: A Multicenter Retrospective Cohort Study

Официальное название

Official Title: Effect of oXiris Hemofilter Use in Septic Shock: A Multicenter Retrospective Cohort Study Using a Target Trial Emulation Approach

Обзор

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.

Подробное описание

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.

Первичные конечные точки

• In-hospital Mortality [Срок оценки: From the initiation of CRRT (Time zero) until hospital discharge or death.]

Вторичные конечные точки (5)

• 3-day Cumulative Fluid Balance [Срок оценки: 3 days after CRRT initiation.]
• Time to Vasopressor Weaning [Срок оценки: From CRRT initiation through ICU discharge, up to 28 days]
• Organ Dysfunction Improvement [Срок оценки: Baseline (Day 0) and Days 1, 2, 3, 7 of ICU stay.]
• Changes in Inflammatory Markers [Срок оценки: Baseline (Day 0) and Days 1, 2, 3, 7 of ICU stay.]
• Renal Recovery Status [Срок оценки: From CRRT initiation through hospital discharge, up to 90 days]

Критерии участия

Критерии включения

• 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).

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

South Korea · 1 центр

• Seoul National University Bundang Hospital — Seongnam-si

Публикации

• Wang G, He Y, Guo Q, Zhao Y, He J, Chen Y, Chen W, Zhou Y, Peng Z, Deng K, Guan J, Xie W, Chang P, Liu Z. Continuous renal replacement therapy with the adsorptive oXiris filter may be associated with the lower 28-day mortality in sepsis: a systematic review and meta-analysis. Crit Care. 2023 Jul 9;27(1):275. doi: 10.1186/s13054-023-04555-x. PMID 37424026
• Zhang L, Srisawat N, Lee CC, Lee DH, Lee K, Liu Z, Mohamad Nor FS, Mustafar RB, Peerapornratana S, Pham HM, Sewa SDW, Tang GKY, Yeh YC, Zhu M, Yao Q, Wang M, Bellomo R. Extracorporeal Blood Purification with the oXiris(R) Filter for Patients with Sepsis and Hyperinflammatory Conditions: The Asia-Pacific oXiris Expert Meeting 2024 Consensus Statements. Blood Purif. 2025;54(11):621-638. doi: 10.1159 PMID 40929000
• Ankawi G, Neri M, Zhang J, Breglia A, Ricci Z, Ronco C. Extracorporeal techniques for the treatment of critically ill patients with sepsis beyond conventional blood purification therapy: the promises and the pitfalls. Crit Care. 2018 Oct 25;22(1):262. doi: 10.1186/s13054-018-2181-z. PMID 30360755
• Chen J, Zhang Z, Gao J, Liu Y, Zhu B, Gao Y, Zhuang Y, Zhu M. A multicentre, randomised controlled clinical trial evaluating the effect of the adsorptive filter oXiris on haemodynamics in abdominal septic shock patients requiring continuous renal replacement therapy (Oxiris for Abdominal SEptic Shock study). BMJ Open. 2025 Jul 8;15(7):e094792. doi: 10.1136/bmjopen-2024-094792. PMID 40633959

Идентификаторы

NCT: NCT07539883 · B-2602-1024-103

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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