BOSTON, MA—Investigational soluble solid dispersion (SSD) oral rifaximin immediate-release (IR 40mg) is associated with a reduced risk of hospitalization and death among patients with cirrhosis and well-controlled ascites, reported authors of a randomized, double-blind, placebo-controlled Phase 2 trial at The Liver Meeting® 2016.
“Rifaximin SSD IR 40mg for up to 24 weeks was well-tolerated and superior to placebo in preventing hospitalizations or mortality in patients with cirrhosis and well-controlled ascites,” reported Jasmohan S. Bajaj, MD, of Virginia Commonwealth University, in Richmond, NC.
There is a pressing need for treatments that can reduce further decompensation and liver disease burden, Dr. Bajaj noted. Rifaximin is a non-systemic antibiotic with a current indication of reducing recurrence risk of overt hepatic encephalopathy (HE) in adults. The research team evaluated the efficacy and safety of SSD oral rifaximin in immediate-release (IR) or extended-release (SER) tablet form, among adults age 18 or older who have liver cirrhosis and well-controlled ascites. Inclusion criteria included a Model for End-Stage Liver Disease (MELD) score of ≥12, or a Child-Pugh B classification score of 7–9.
Exclusion criteria included cirrhosis-related esophageal variceal bleeding or clinically significant gastrointestinal bleeding, spontaneous bacterial peritonitis, renal failure or the presence of monomicrobial culture in ascites fluid, and medically-refractory ascites.
Patients were randomly assigned to a placebo group or 1 of 5 rifaximin SSD study groups: IR 40mg, IR 80mg, SER 40mg, SER 80mg, or IR 80mg+SER 80mg. Tablets were taken every night at bedtime for 24 weeks. The study included a 2-week post-treatment period.
Of 518 patients randomized to study groups, 408 (78.8%) completed the study. Cirrhosis etiology was not evenly represented across the 6 study groups. For example, only 9.5% of SER 40mg group patients had both viral hepatitis and alcohol etiologies, compared to 17% in the SER 80mg group. The IR 40mg study group had a higher proportion of men and patients with alcohol-only etiology than other study groups.
Study findings indicate that only patients in the SSR IR 40mg group may have benefitted from treatment (24-week risk of hospitalization or all-cause mortality: odds ratio [OR] 0.48; 95% CI: 0.24–0.94; P=0.03).
“Rifaximin SSD IR 40mg reduced the risk of hospitalization or all-cause mortality by 52% vs. placebo during 24 weeks of treatment,” Dr. Bajaj reported. “No significant differences were observed for other treatment groups vs. placebo. Significantly fewer patients treated with rifaximin SSD IR 40mg vs. placebo experienced an episode of HE (2.6% [n=2] vs. 12.8% [n=12]; P=0.01).”
Rifaximin SSD IR 40mg also appeared to be the best-tolerated regimen studied, Dr. Bajaj noted.
No statistical comparisons were presented, but quantitatively, the any-adverse-event (AE) rates for the study groups were 73% for IR 40mg, 75.8% for IR 80mg, 77.4% for SER 40mg, 79.8% for 80mg SER, and 85% for patients in the combination IR/SER group. The AE rate for patients receiving placebo was 77.7%.
Pruritus occurred in only 1 (1.3%) patient in the IR 40mg group, compared to 6% to 13.8% in the other study groups. Headache and insomnia occurred in 10.3% and 12.8% of the IR 40mg group patients, respectively compared to between 3.8% and 8.3% for headache and 2.5% and 7.4% for insomnia in the other study arms.
Salix Pharmaceuticals funded the research and Dr. Bajaj disclosed that he serves as a consultant for the company.