O09 A double blind, randomised, placebo-controlled study to assess safety and tolerability of oral enterosorbent Carbalive (Yaq-001) in cirrhotic patients

Background Yaq-001 is a non-absorbable, synthetic carbon with high adsorptive capacity for bacterial products including lipopolysaccharide (LPS) and pro-inflammatory cytokines. Studies in cirrhotic rats showed reduced endotoxemia, improvements end-organ dysfunction sensitisation to LPS. The aims of this study were evaluate the safety tolerability decompensated (DC) patients characterise immunological metabolic effects. Methods This EU-funded H2020 (CARBALIVE:634579) recruited diuretic-responsive ascites. 28-patients from 8-EU centres randomised receive 4 g (Y) or placebo (P) 12-weeks. Safety assessments performed at baseline, weeks 1, 4, 8 12. Endotoxin activity assay (EAA, data used analysis: CV<20%), organ function, nutrition, markers systemic gut inflammation, permeability, urinary 1HMRS, next generation sequencing stool evaluated W4 W12. Data summarized by group visit as means (SD) select efficacy parameters modeled using MMRM. Results 14-patients each (Y: Age: 57.8±7 yrs, M: 71%, MELD: 12.4±0.9; P: 57.3±10, 75%, 13.9±1). Safety: was well tolerated no SAEs, stable MELD score, decompensation events nutritional status. Compliance: 93%(Y) 67%(P). Endotoxemia: Trends reduction EAA ratio (Y:-2.4% vs P:29.6%) constitutive whole blood ROS (Y:-37.3% P:+34.3%) observed active (figure 1). Systemic inflammation: Reductions WCC, CRP, IL6 CXCL10 compared (Y(%):-8.8,-4.3,-3.6,-16.7; P(%)+0.4,+23.9,+13.8,+31.8) Gut inflammation/permeability: Improvements faecal cytokines trended towards published values healthy control. Reduction plasma D-lactate suggestive an improvement barrier integrity Metabolism: ammonia trend increased hippurate. Microbiome: No change diversity observed. Conclusion safe tolerated. suggest proof mechanism that Yaq-001, modulates endotoxemia inflammation impacting its permeability.