Rifaximin ‘cannot be recommended’ as antibiotic prophylaxis for severe cirrhosis, ascites
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Key takeaways:
- 12-month transplant-free survival rates were similar between patients who received rifaximin and those on placebo (58% vs. 64.9).
- Adverse events led to drug discontinuation in 44.6% vs. 41.98%.
Although rifaximin was well-tolerated in patients with severe cirrhosis and ascites, it did not improve transplant-free survival and cirrhosis-related complications and “cannot be recommended” as antibiotic prophylaxis, a researcher noted.
“Bacterial infections in cirrhotic patients represent the most important precipitating event for acute decompensation and account for significant mortality,” Thierry Thévenot, MD, PhD, from the department of hepatology at Besançon Regional University Hospital Center in France, told Healio. “One of the most common infections is spontaneous bacterial peritonitis (SBP). Although primary antibiotic prophylaxis for SBP is recommended by EASL and AASLD practice guidelines in highly selected cirrhotic patients, this practice is not routinely used and practitioners probably fear the growing prevalence of bacterial resistance, especially to fluoroquinolones.”
In the phase 3, double-blind, placebo-controlled ProPILA-Rifax study presented at EASL Congress, Thévenot and colleagues randomly assigned 159 patients with severe cirrhosis with grade 2 or 3 ascites and low protein level in ascites (< 15 g/L) to twice-daily rifaximin 550 mg (n = 72) or placebo (n = 80) for 12 months, as primary SBP prophylaxis. Baseline characteristics of participants were well-balanced.
The primary endpoint was 12-month transplant-free survival, and secondary endpoints were hospital mortality, 3- and 6-month transplant-free survival, incidence of cirrhosis complications and safety of rifaximin.
“In the modified intention-to-treat population, the transplant-free survival at 12 months was not significantly different between the two groups,” Thévenot said, with rates of 58% reported in the rifaximin group vs. 64.9% in the placebo group.
In addition, preliminary data showed transplant-free survival rates between rifaximin and placebo groups at 3 and 6 months were 82.2% vs. 74.7% and 75% vs. 68.4%, respectively.
According to researchers, 31 patients who received rifaximin died during the study, as did 30 who received placebo; however, deaths were unrelated to the study drug. In each group, seven patients required transplantation.
Further, no significant differences were noted between groups in incidence of infections, hepatorenal syndrome, hepatic encephalopathy and variceal bleeding. Adverse events were similar between the groups as well and led to drug continuation in 44.6% of patients on rifaximin and 41.98% on placebo, researchers reported.
“At this time, rifaximin cannot be recommended for the primary antibiotic prophylaxis of SBP in severe cirrhotic patients,” Thévenot told Healio. “However, we need to analyze our data in the per protocol population based on the compliance of the study drug.”
He added: “Currently, practitioners need to follow the recommendations proposed by EASL regarding the primary antibiotic prophylaxis of SBP. However, considering the high prevalence of bacterial resistance across the world, practitioners should prescribe antibiotics cautiously and probably not prescribe in noncompliant patients or in patients with limited life expectancy.”
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Thévenot T, et al. Effect of rifaximin in severe cirrhotic patients with ascites: A double-blind randomized placebo-controlled phase 3 trial. Presented at: EASL Congress; June 5-8, 2024; Milan (hybrid meeting).
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