NCT04082780

Rifamycin in Minimal Hepatic Encephalopathy

A Double-Blind Randomized Placebo-Controlled Trial of Rifamycin SV MXX in Minimal Hepatic Encephalopathy (RIVET Trial)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center · Federal
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a randomized double-blind placebo-controlled trial of MHE in patients with cirrhosis using rifamycin SV-MMX 600mg BID vs placebo for 30 days with PK, safety, microbiota, brain function and brain MRI endpoints.

Detailed description

Hepatic encephalopathy (HE) is a highly prevalent neuro-cognitive complication of cirrhosis characterized by cognitive dysfunction, and high rate of subsequent mortality and recurrence. HE also places a tremendous burden with a relentless increase in inpatient stay duration with charges topping $7244.7 million in 20092. There were almost 23,000 hospitalizations for HE in 2009 and far more patients with HE who are being managed as an outpatient in the US. In the NACSELD (North American Consortium for the Study of End-Stage Liver Disease) experience, HE in inpatients is an independent risk factor for mortality and the leading cause of readmissions in patients with cirrhosis. HE has two major phases, covert or minimal HE (MHE), which is only recognized by specialized tests and overt HE (OHE), which is clinically obvious. OHE forms the tip of the iceberg, while MHE affects as many as 60% of tested patients with cirrhosis. MHE is associated with changes in specific cognitive domains that result in altered health-related quality of life and daily function. This can promote the development of OHE, impair driving and employment, increase falls and is independently associated with a risk of hospitalizations and mortality. There is an alteration of gut microbial composition and function (bile acid changes, endotoxemia and gut metabolic products) in cirrhosis, which worsens with disease progression with MHE and OHE. Current treatments for OHE are mostly focused on the gut, including lactulose and rifaximin. However, despite extracting a major toll on disease progression, there is no current guideline to treat MHE. Prior studies using lactulose and rifaximin have been performed in this setting with improvement in brain function, brain MRI changes and microbial function. However, these are still not standard of care. Rifamycin SV MMX® 200 mg is a gut-specific antibiotic with a long track record of safety that has been FDA approved for the treatment of traveler's diarrhea. Unlike rifaximin, rifamycin-SV MMX mostly affects the colon, where the bacterial load is much larger than in the other parts of the GI tract. The impact of rifamycin on MHE has not been studied to date. This is a randomized double-blind placebo-controlled trial of MHE in patients with cirrhosis.

Conditions

• Hepatic Encephalopathy
• Cirrhosis, Liver

Interventions

Type	Name	Description
DRUG	Rifamycin SV MMX	Intervention arm
OTHER	Placebo	Placebo arm

Timeline

• Start date: 2019-09-01
• Primary completion: 2023-04-28
• Completion: 2023-04-28
• First posted: 2019-09-09
• Last updated: 2023-09-21

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study