Rifaximin for Hepatic Encephalopathy

(RED-C-3132 Trial)

Recruiting at 241 trial locations

Overseen By Nupur Murali

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bausch Health Americas, Inc.

Disqualifiers: Active COVID-19, SBP, EVB, AKI-HRS, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

466 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if rifaximin, an oral antibiotic, can delay brain problems in patients with liver cirrhosis and controlled fluid buildup by reducing harmful gut bacteria. Rifaximin has been shown to reduce the recurrence of brain-related issues and related hospitalizations.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Rifaximin SSD for hepatic encephalopathy?

Research shows that Rifaximin is effective in reducing the risk of hepatic encephalopathy (a brain disorder caused by liver disease) and decreases hospital visits for patients waiting for a liver transplant. ^{1 2 3 4 5}

Is rifaximin safe for humans?

Rifaximin has been studied for safety in treating hepatic encephalopathy, and research generally supports its safety in humans. Multiple studies, including those conducted in different populations, have evaluated its safety profile, indicating it is well-tolerated. ^{3 5 6 7 8}

What makes the drug Rifaximin SSD unique for treating hepatic encephalopathy?

Rifaximin SSD is unique because it targets the gut microbiota, which plays a role in hepatic encephalopathy, by reducing the production of toxins that can affect brain function. This approach is different from other treatments that may not specifically focus on altering gut bacteria. ^{9 10 11 12 13}

Research Team

Michael Mader

Principal Investigator

Bausch Health

Eligibility Criteria

This trial is for adults aged 18-85 with liver cirrhosis and controlled fluid buildup in the abdomen. Participants must have a clear mental state (MMSE score >24) and no severe brain dysfunction (Conn score <2). Those with recent serious infections, internal bleeding, kidney issues, or past overt hepatic encephalopathy are excluded.

Inclusion Criteria

Your memory and thinking skills are good, and you score more than 24 on a test called Mini-Mental State Examination (MMSE).

I have liver cirrhosis with stable fluid buildup not needing fluid removal.

I am between 18 and 85 years old.

Exclusion Criteria

I currently have COVID-19.

I have a history of spontaneous bacterial peritonitis.

You have a history of severe liver swelling (Conn score ≥ 2).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either rifaximin SSD-40mg IR or placebo to assess efficacy and safety for delaying overt hepatic encephalopathy decompensation

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Rifaximin SSD

Trial Overview The study compares Rifaximin SSD-40mg IR against a placebo to see if it can delay the first episode of overt hepatic encephalopathy—a severe liver-related brain disorder—in patients with liver cirrhosis. It's randomized and double-blind, meaning neither doctors nor patients know who gets the real treatment.

Participant Groups

Group I: Rifaximin SSD-40mg IR Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Bausch Health Americas, Inc.

Lead Sponsor

Trials

265

Recruited

82,000+

Dr. Jonathan Sadeh

Bausch Health Americas, Inc.

Chief Medical Officer

MD from Mount Sinai School of Medicine, MSc in Clinical Research from Harvard Medical School

Thomas J. Appio

Bausch Health Americas, Inc.

Chief Executive Officer since 2021

Bachelor's degree in Biology from Rutgers University

Findings from Research

Rifaximin has been shown to be more effective than lactulose in treating hepatic encephalopathy (HE), with studies indicating it leads to fewer hospitalizations and lower healthcare costs.

The safety profile of rifaximin is favorable, as it is better tolerated compared to other treatments like paromomycin and neomycin, making it a promising option for patients with liver failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifaximin for treatment of hepatic encephalopathy. Maclayton, DO., Eaton-Maxwell, A.[2018]

Rifaximin is effective in improving symptoms of hepatic encephalopathy, showing superior and faster results compared to traditional treatments like lactulose, and it also reduces hospitalization needs and costs.

The treatment is generally well-tolerated, with mostly minor gastrointestinal side effects, making it a safer option compared to other medications for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifaximin for the treatment of hepatic encephalopathy. Lawrence, KR., Klee, JA.[2022]

A meta-analysis of 8 randomized controlled trials with 407 patients found that rifaximin is at least as effective as nonabsorbable disaccharides for treating hepatic encephalopathy, with significant improvements in grades of portosystemic encephalopathy.

Rifaximin demonstrated better safety compared to nonabsorbable disaccharides, indicating it may be a preferable treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifaximin versus Nonabsorbable Disaccharides for the Treatment of Hepatic Encephalopathy: A Meta-Analysis. Wu, D., Wu, SM., Lu, J., et al.[2022]

Rifaximin significantly improved blood ammonia levels and the portal systemic encephalopathy index in Japanese patients with hepatic encephalopathy (HE) during a 14-day treatment period, demonstrating its efficacy.

The treatment was well tolerated, with only 13.4% of patients experiencing adverse drug reactions, none of which were severe enough to cause death, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rifaximin in Japanese patients with hepatic encephalopathy: A phase II/III, multicenter, randomized, evaluator-blinded, active-controlled trial and a phase III, multicenter, open trial. Suzuki, K., Endo, R., Takikawa, Y., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Durability of rifaximin response in hepatic encephalopathy. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Rifaximin reduces the incidence of spontaneous bacterial peritonitis, variceal bleeding and all-cause admissions in patients on the liver transplant waiting list. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Rifaximin for treatment of hepatic encephalopathy. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Rifaximin vs. conventional oral therapy for hepatic encephalopathy: a meta-analysis. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Rifaximin for the treatment of hepatic encephalopathy. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy: a double-blind, randomized, dose-finding multi-centre study. [2022]

7. Egypt pubmed.ncbi.nlm.nih.gov

Rifaximin versus Nonabsorbable Disaccharides for the Treatment of Hepatic Encephalopathy: A Meta-Analysis. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rifaximin in Japanese patients with hepatic encephalopathy: A phase II/III, multicenter, randomized, evaluator-blinded, active-controlled trial and a phase III, multicenter, open trial. [2020]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Shunaoxin dropping pill improves cognitive functions of rats with chronic cerebral hypoperfusion via the microbiota-gut-brain axis. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Efficacy of oral hydergine (ergoloid mesylates) in alcohol related encephalopathy. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Study protocol for a phase III randomised controlled trial of Sailuotong (SLT) for vascular dementia and Alzheimer's disease with cerebrovascular disease. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Shen-zhi-ling oral liquid improves behavioral and psychological symptoms of dementia in Alzheimer's disease. [2021]

13. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Treatment of cognitive and non-cognitive symptoms in cerebrovascular disease]. [2021]