Efficacy and safety of double plasma cytokine adsorption system with sequential low-volume plasma exchange in treating acute-on-chronic liver failure complicated by sepsis: protocol for a multicentre randomised controlled clinical trial

Introduction: Acute-on-chronic liver failure (ACLF) and sepsis are both life-threatening clinical syndromes that frequently coexist. Patients with ACLF complicated by sepsis experience significantly higher mortality rates, yet therapeutic options remain limited. This randomised controlled trial aims to evaluate the efficacy and safety of the double plasma cytokine adsorption system with sequential low-volume plasma exchange (DPCAS+LPE) in patients with ACLF complicated by sepsis.

Methods and analysis: This is a multicentre, prospective, open-label, parallel-group, randomised clinical trial. A total of 192 patients with ACLF complicated by sepsis will be recruited from five hospitals in China. Participants will be randomly assigned (1:1) to either the intervention group or the control group. Both groups will receive standard medical treatment and three sessions of artificial liver support system (ALSS) therapy administered every other day. The intervention group will receive two sessions of DPCAS+LPE followed by one session of plasma exchange (PE), while the control group will receive three sessions of PE. The primary outcome is the 4-week mortality rate. Secondary outcomes include the 12-week mortality rate; longitudinal changes in Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, Model for End-Stage Liver Disease and Chinese Group on the Study of Severe Hepatitis B-associated ACLF II scores; and the Vasoactive-Inotropic Score at weeks 1, 2, 3 and 4 post baseline. Furthermore, the clearance rates of various cytokines and lactate will be measured after the first ALSS session. Safety will be assessed by documenting and managing all adverse events throughout the study.