- Design
- Randomised, double-blind, placebo-controlled pilot trial (RIVET)
- Population
- 30 adults with compensated cirrhosis
- Primary outcome
- Change in gut antimicrobial resistance genes after 30 days
- Effect
- No significant change vs placebo after false discovery rate correction
RIVET was a small double-blind trial: 30 people with compensated cirrhosis received rifamycin SV MMX, a gut-targeted rifamycin, or placebo for 30 days. Stool shotgun metagenomic sequencing before and after mapped antimicrobial resistance genes.
After correction for multiple testing, there was no significant change in resistance genes compared with placebo. Some vancomycin resistance genes trended downward; some Enterobacteriaceae efflux genes rose nominally, but not after correction. There was no increase in infections or safety concerns.
The question matters because long-term rifaximin is standard for hepatic encephalopathy, and preclinical work has raised the possibility of resistance gene expansion. This trial used a different rifamycin formulation in compensated disease, so it does not settle the rifaximin question. It is a hypothesis-generating pilot.
- Keep rifaximin where indicated for hepatic encephalopathy; this trial gives no reason to stop it.
- Treat resistance-gene concerns with gut-targeted rifamycins as unresolved, not disproved.
- Note that the drug tested was rifamycin SV MMX, not rifaximin.
- Minimise other antibiotic exposure in cirrhosis, which does drive resistance.
Why it matters
Long-term gut-targeted antibiotics in cirrhosis carry a resistance question nobody has yet answered.
Don't overread it
Thirty patients for 30 days, and a different drug from rifaximin; this is a pilot.
The statistics, in plain English
With 15 people per group over 30 days, the trial could only detect large shifts. False discovery rate correction is used when many genes are tested at once, to avoid chance findings; the nominal increases did not survive it, so they may be noise.
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