Background
Novel therapies are needed to treat HE, and microbiome modulation is a promising target. VE303 is a defined consortium of 8 purified, clonal bacterial strains, known to produce metabolites that may be beneficial in HE. We evaluated the safety and efficacy of VE303 to treat HE.
Conclusions
VE303 was well tolerated in patients with cirrhosis and a history of overt HE, leading to the engraftment of certain VE303 strains and a higher percentage of patients with improved PHES.
Methods
We performed a single-center, randomized, placebo-controlled trial of VE303 in adult patients with a history of overt HE (NCT04899115). Eligible patients were taking lactulose and rifaximin, had no recent systemic antibiotics, and had MELD ≤20. All patients received 5 days of oral vancomycin followed by randomization to 14 days of VE303 or placebo (2:1). The primary endpoints were incidence of serious adverse events and change in psychometric HE score (PHES) from baseline to 4 weeks after treatment. Stool samples underwent metagenomic sequencing and metabolite quantification.
Results
Eighteen patients completed the trial, 56% men, with a mean age of 59 years and a mean MELD of 11. Patients who received VE303 had a mean change in PHES of +1.5 versus -1.0 in those who received a placebo (p=0.20). Two of the 12 patients who received VE303 had at least 1 serious adverse event (all overt HE hospitalizations), compared with 0/6 patients who received a placebo. In the patients who received VE303, 2 of 8 strains engrafted in >50% of patients. Both VE303 strain engraftment and increased stool butyrate production had a trend toward improved PHES. Conclusions: VE303 was well tolerated in patients with cirrhosis and a history of overt HE, leading to the engraftment of certain VE303 strains and a higher percentage of patients with improved PHES.