Rifaximin for Hepatic Encephalopathy

(RED-C-3132 Trial)

Not currently recruiting at 272 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well rifaximin SSD can delay serious mental confusion in people with liver cirrhosis. Liver cirrhosis scars the liver, impairing its function, and can lead to hepatic encephalopathy, which affects brain function. Participants will receive either rifaximin SSD or a placebo (a pill with no active medicine) to determine if the medication can prevent the first serious episode of this brain condition. Candidates may be suitable if they have liver cirrhosis with controlled fluid buildup in the abdomen and have not experienced serious confusion episodes. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that rifaximin is generally safe for people. A large study found that rifaximin helps prevent repeat episodes of hepatic encephalopathy, a brain disorder caused by liver problems, without increasing side effects. Another study demonstrated that rifaximin did not lead to more negative reactions in patients. Rifaximin is also approved for reducing the risk of this brain disorder recurring, suggesting it is well-tolerated. Some studies have even found that people taking rifaximin had a lower risk of diarrhea compared to other treatments. Overall, the evidence supports the safety of rifaximin for people with liver issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hepatic encephalopathy?

Rifaximin SSD-40mg IR is unique because it offers a new formulation of the antibiotic rifaximin, which is already used to manage hepatic encephalopathy. Unlike traditional options like lactulose or standard rifaximin, this new form is designed for immediate release, potentially allowing for quicker symptom control. Researchers are excited because this could mean faster relief for patients, enhancing their quality of life while maintaining the effectiveness of the drug.

What evidence suggests that rifaximin SSD might be an effective treatment for hepatic encephalopathy?

Research has shown that rifaximin can greatly reduce the risk of hepatic encephalopathy (HE), a brain disorder caused by liver disease. In this trial, participants will receive either Rifaximin SSD-40mg IR or a placebo. Studies indicate that over six months, rifaximin proves more effective than a placebo at keeping patients free from HE. It helps prevent both the first episode of HE and its recurrence. However, while rifaximin effectively prevents HE, it does not reduce the risk of death or increase side effects. Overall, rifaximin offers a promising treatment for managing HE in people with liver cirrhosis. ^{2 6 7 8 9}

Who Is on the Research Team?

Michael Mader

Principal Investigator

Bausch Health

Are You a Good Fit for This Trial?

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.

You do not have severe liver disease.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10910798/

Preventive and therapeutic effects of rifaximin on hepatic ... The results showed that rifaximin was able to significantly reduce the risk of HE occurrence in primary prevention, recurrence in secondary ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa0907893

Rifaximin Treatment in Hepatic Encephalopathy Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo.

3. journals.lww.com journals.lww.com/md-journal/fulltext/2025/01310/efficacy_and_safety_of_rifaximin_for_the.26.aspx

Efficacy and safety of rifaximin for the prophylaxis of... Rifaximin is beneficial for primary and secondary prevention of HE, but it does not reduce mortality or increase the incidence of adverse events.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39889173/

Efficacy and safety of rifaximin for the prophylaxis ... Rifaximin helped prevent HE (RR = -0.47, 95% confidence interval [CI]: -0.68 to -0.26) in patients with cirrhosis, but did not reduce mortality ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05297448

Evaluation of Rifaximin SSD for Delaying Encephalopathy ... A Phase 3, randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of rifaximin SSD-40mg IR for the delay of the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3964161/

Safety, efficacy, and patient acceptability of rifaximin for ... A large randomized trial found that rifaximin prevents recurrent episodes of hepatic encephalopathy. Most patients were treated concurrently with lactulose.

7. xifaxan.com xifaxan.com/hcp/ohe/safety-and-dosing/

Safety and Dosing for Overt HE | XIFAXAN® (rifaximin) XIFAXAN® (rifaximin) 550 mg tablets are indicated for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults. IMPORTANT SAFETY ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00298038

Study Details | NCT00298038 | A 6-month Efficacy, Safety ... The purpose of this study is to determine if the study drug is safe and effective in preventing hepatic encephalopathy (HE).

9. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0323359

Efficacy and safety of rifaximin in preventing hepatic ... In terms of adverse effects, RFX was associated with a lower risk of diarrhea than NADs (RR = 0.04, 95% CI: 0.00–0.25). So, RFX therapy is effective and well- ...