Rifaximin has no effect on hemodynamics in decompensated cirrhosis - A randomized, double blind, placebo controlled trial

BACKGROUND AND RATIONALE: Decompensated cirrhosis is characterized by disturbed systemic and splanchnic hemodynamics. Bacterial translocation from the gut is considered the key driver in this process. Intestinal decontamination with rifaximin may improve hemodynamics. This double-blind, randomized, controlled trial investigates the effects of rifaximin on hemodynamics, renal function and vasoactive hormones.

METHODS: We randomized 54 stable out-patients with cirrhosis and ascites to rifaximin 550 mg BD (n=36) or placebo BD (n=18). Forty-five patients were male, mean age 56 years (±8.4), the average Child score 8.3 (±1.3), and the MELD score 11.7 (±3.9). Measurements of hepatic venous pressure gradient (HVPG), cardiac output, and systemic vascular resistance (SVR) were performed at baseline and after 4 weeks. The glomerular filtration rate (GFR), plasma renin, noradrenaline, lipo-polysaccharide binding protein (LBP), troponin T and brain natriuretic peptide levels were measured.

RESULTS: Rifaximin had no effect on HVPG, mean 16.8 ±3.8 mmHg at baseline vs. 16.6 ±5.3 mmHg at follow-up compared to the placebo, mean 16.4 ±4 mmHg at baseline vs. 16.3 ±4.4 mmHg at follow-up, p=0.94. No effect was found on the cardiac output, mean 6.9 ±1.7 l/min at baseline vs. 6.9 ±2.3 l/min at follow-up compared to the placebo, mean 6.6 ±1.9 l/min at baseline compared to 6.5 ±2.1 l/min at follow-up, p=0.66. No effects on the GFR p=0.14 or the vasoactive hormones were found. Subgroup analyses on patients with increased LBP and SVR below the mean (1011 dynes x s/cm(5) ) revealed no effect of rifaximin.

CONCLUSIONS: Four weeks of treatment with rifaximin did not reduce the HVPG or improve systemic hemodynamics in patients with cirrhosis and ascites. Rifaximin did not affect GFR or levels of vasoactive hormones. ClinicalTrials.gov (NCT01769040). This article is protected by copyright. All rights reserved.