Efficacy and Safety Study of CA330 Hemoadsorption Device on IL-6 Removal in Septic Patients

Overview

Sepsis persists to be the leading causes of morbidity and mortality worldwide. Moreover, the magnitude of health care resources utilized when managing septic patients is huge. All these hard facts call for constant efforts to optimize therapy. At present, the definitive therapy is adequate antibiotics and infectious source control. Fortunately, research has led to a better understanding of the pathophysiology of sepsis, in which the activation of multiple pro- and anti-inflammatory mediators plays a key role. This has led to the development of treatment strategies aimed at restoring a balanced immune response by eliminating/deactivating these inflammatory mediators. Whilst animal models of sepsis have provided encouraging results with strategies aiming at immune response modulation, clinical studies in patients using targeted pharmacological approaches have so far proved disappointing. Besides of acute kidney injury (AKI), renal replacement therapy (RRT) is applied to remove inflammatory mediators extracorporeally. Across the different modalities, the application of adsorption may help deactivate and decrease the peak elevation of these mediators in earlier course of sepsis, when levels of endotoxins and cytokines are extremely high. Recently, attempts to improve the outcome of sepsis patients with such devices, ie CytoSorb cytokine hemoadsorption and polymyxin B (Toraymyxin) endotoxin adsorption, have seen a certain renaissance. However, the clinical evidence to date supporting hemoadsorption for removal of endotoxins and/or proinflammatory mediators in sepsis remains incompetent and controversial. CA330 (Jafron Biomedical Co , Ltd, Zhuhai, China) is a hemoadsorption device containing hemocompatible, porous polymeric beads capable of removing cytokines and other mid-molecular weight toxins from blood by size exclusion and surface adsorption. Compared with HA330, improved resin synthesis technology makes CA330 a better performance in removing cytokines. This trial is the first to evaluate CA330 efficacy of cytokine reduction using the change in plasma interleukin (IL)-6 concentrations over time as a primary outcome. Although the trial was neither designed nor powered to evaluate outcome, we also evaluated organ function parameters as well as 28-day all-cause mortality.

Eligible patients are stratified by site and randomly assigned in a 1:1 ratio to either CA330 hemoperfusion plus conventional medical therapy group or conventional medical therapy group. The randomization is performed by researchers on the central randomization system, provided by the Department of Biostatistics, Southern Medical University. In this study, the center coded random number table is produced by stratified and sectional randomization method. Statistical Analysis System(SAS) 9.4 statistical software is used to generate random coding tables with serial numbers (001-144) according to the number of cases allocated in each center and the proportion of experimental group and control group (1:1). The length of selected sections (block) and random seed number are sealed together as confidential data . The random number table is provided by the statisticians of the Department of Biostatistics, Southern Medical University. The experimental group receive routine treatment of sepsis combined with cytokine adsorption column (CA330) perfusion, and the control group receive routine treatment of sepsis only. Hemoperfusion treatments are performed using a perfusion machine via centrally inserted standard dialysis catheters at a prescribed blood flow rate of 100-300ml/min. In the beginning, lower flow rate is recommended, if there is no discomfort, then gradually increases. Each patient received 2 hemoperfusion treatments within 24 hours with a target duration for each treatment of 120-180 minutes (minimum of 120 minutes). The shorter the interval between the two hemoperfusion is, the better. It is suggested that the second hemoperfusion be performed within 0-5 hours after the first one. Anticoagulation was recommended with low-molecular-weight heparin in arterial line of the circuit at the dose of 60-80 international units (IU)/kg. No additional dose is required. The activity of anticoagulant factor α can be monitored at 60 minutes. It is suggested that the activity of anticoagulant factor α should be maintained at 500-1000units/L in subjects without bleeding tendency and 200-400units/L in subjects with bleeding tendency. If the clinical condition is limited, it is not mandatory to monitor this parameter.