A 6-month Efficacy, Safety, and Tolerability Study of Rifaximin In Preventing Hepatic Encephalopathy

NCT00298038 | Completed Phase 3 Results DMC

• 1 other identifier: RFHE3001
• Study Type: interventional
• Target: 299
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to determine if the study drug is safe and effective in preventing hepatic encephalopathy (HE).

Conditions

Hepatic Encephalopathy

Outcome Measures

Primary Outcomes (1)

• Time To The First Breakthrough Overt HE Episode

  Time to a breakthrough overt HE episode was the duration (number of days) from time of first dose of study drug to the first breakthrough overt HE episode. A breakthrough overt HE episode was defined as an increase of Conn score from Grade 0 or 1 to ≥2, or an increase in Conn and asterixis score of 1 grade each for those participants who entered the study with a Conn score of 0. Participants who completed the study and did not experience a breakthrough overt HE episode were censored at the time of their 6-month visit. Participants who terminated early for reasons other than a breakthrough overt HE episode were contacted at 6 months from randomization to determine if they had experienced a breakthrough overt HE event or other outcome. Participants without breakthrough overt HE were censored at the time of last contact or death, whichever was earlier. The number of events of a first breakthrough overt HE episode during the treatment interval is presented.

  Baseline up to 6 Months (168 days)

Secondary Outcomes (5)

• Time To First HE-related Hospitalization

  Baseline up to 6 months

• Time To Any Increase From Baseline In Conn Score

  Baseline up to 6 months

• Time To Any Increase From Baseline In Asterixis Grade

  Baseline up to 6 months

• Mean Change From Baseline In Fatigue Domain Score On The CLDQ At End Of Treatment

  Baseline, 6 months (End Of Treatment)

• Mean Change From Baseline In Venous Ammonia Concentration At End Of Treatment

  Baseline, Month 6 (End Of Treatment)

Study Arms (2)

Rifaximin

EXPERIMENTAL

Participants were administered a single rifaximin 550 milligram (mg) tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.

Drug: Rifaximin

Placebo

PLACEBO COMPARATOR

Participants were administered a single matching placebo tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.

Drug: Placebo

Interventions

Rifaximin DRUG

Oral

Also known as: Xifaxan®

Rifaximin

Placebo DRUG

Oral

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must sign an Informed Consent Form
• In remission from past HE
• Uses appropriate birth control measures
• More than or equal to 18 years of age
• Must have potential to benefit from treatment
• Recent prior HE episodes
• Capable and willing to comply with all study procedures
• Participant has personal support available
• Has a certain Model End Stage Liver Disease (MELD) score
• Recent transjugular intrahepatic portosystemic shunt (TIPS) placement or revision

You may not qualify if:

• Significant medical conditions, medical conditions that may impact study participation, or Investigator decision not to include
• Allergies to the study drug or similar drugs
• Laboratory abnormalities
• Recent participation in another clinical trial
• History of non-compliance
• Pregnant or at risk of pregnancy, or is lactating
• Recent alcohol consumption
• Active bacterial or viral Infections
• Bowel issues
• Active malignancy
• On a prohibited medication
• Liver transplant expected in near term
• Lactulose intolerance
• Participant shows presence of intestinal obstruction or has inflammatory bowel disease
• Ongoing or recent GI bleed

Sponsors & Collaborators

• Bausch Health Americas, Inc.: lead

Related Publications (4)

• Zacharias HD, Kamel F, Tan J, Kimer N, Gluud LL, Morgan MY. Rifaximin for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2023 Jul 19;7(7):CD011585. doi: 10.1002/14651858.CD011585.pub2.

  PMID: 37467180 DERIVED

• Flamm SL, Mullen KD, Heimanson Z, Sanyal AJ. Rifaximin has the potential to prevent complications of cirrhosis. Therap Adv Gastroenterol. 2018 Sep 28;11:1756284818800307. doi: 10.1177/1756284818800307. eCollection 2018.

  PMID: 30283499 DERIVED

• Sanyal A, Younossi ZM, Bass NM, Mullen KD, Poordad F, Brown RS, Vemuru RP, Mazen Jamal M, Huang S, Merchant K, Bortey E, Forbes WP. Randomised clinical trial: rifaximin improves health-related quality of life in cirrhotic patients with hepatic encephalopathy - a double-blind placebo-controlled study. Aliment Pharmacol Ther. 2011 Oct;34(8):853-61. doi: 10.1111/j.1365-2036.2011.04808.x. Epub 2011 Aug 17.

  PMID: 21848797 DERIVED

• Bass NM, Mullen KD, Sanyal A, Poordad F, Neff G, Leevy CB, Sigal S, Sheikh MY, Beavers K, Frederick T, Teperman L, Hillebrand D, Huang S, Merchant K, Shaw A, Bortey E, Forbes WP. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010 Mar 25;362(12):1071-81. doi: 10.1056/NEJMoa0907893.

  PMID: 20335583 DERIVED

MeSH Terms

Conditions

Hepatic Encephalopathy

Interventions

Rifaximin

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Director of Clinical Operations
• Organization: Bausch Health Companies

Lindsey.Mathew@bauschhealth.com

Study Officials

• Lindsey Mathew

  Bausch Health Companies

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2006
• First Posted: March 1, 2006
• Study Start: December 19, 2005
• Primary Completion: August 15, 2008
• Study Completion: August 15, 2008
• Last Updated: September 18, 2019
• Results First Posted: August 14, 2019

Record last verified: 2019-09