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NCT00298038

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

Completed Phase 3 Results posted Last updated 18 September 2019
What this trial tests

Phase 3 trial testing Rifaximin in Hepatic Encephalopathy in 299 participants. Completed in 15 August 2008.

Timeline
19 December 2005
Primary endpoint
15 August 2008
15 August 2008

Quick facts

Lead sponsorBausch Health Americas, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposeprevention
Enrollment299
Start date19 December 2005
Primary completion15 August 2008
Estimated completion15 August 2008

Drugs / interventions tested

Conditions studied

Sponsor

Bausch Health Americas, Inc. — full company profile →

Who can join

18 and older, any sex, with Hepatic Encephalopathy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time To The First Breakthrough Overt HE Episode Primary · Baseline up to 6 Months (168 days)

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 over

0 to <28 Days
GroupValue95% CI
Rifaximin13
Placebo20
28 to <56 Days
GroupValue95% CI
Rifaximin4
Placebo23
56 to <84 Days
GroupValue95% CI
Rifaximin6
Placebo14
84 to <140 Days
GroupValue95% CI
Rifaximin7
Placebo10
140 to <168 Days
GroupValue95% CI
Rifaximin1
Placebo6
≥168 Days
GroupValue95% CI
Rifaximin0
Placebo0
Time To First HE-related Hospitalization Secondary · Baseline up to 6 months

Time to first HE-related hospitalization is defined as the duration (number of days) between the first dose of study drug and the date of first HE-related hospitalization. Participants who discontinued prior to hospitalization due to HE and prior to completion of the 6-month treatment period were censored at the time of discontinuation. The number of participants with their first HE-related hospitalization per interval is presented. The number of events of the first HE-related hospitalization during the treatment interval is presented.

0 to <28 Days
GroupValue95% CI
Rifaximin4
Placebo11
28 to <56 Days
GroupValue95% CI
Rifaximin4
Placebo12
56 to <84 Days
GroupValue95% CI
Rifaximin4
Placebo7
84 to 140 Days
GroupValue95% CI
Rifaximin5
Placebo4
140 to <168 Days
GroupValue95% CI
Rifaximin2
Placebo2
≥168 Days
GroupValue95% CI
Rifaximin0
Placebo0
Time To Any Increase From Baseline In Conn Score Secondary · Baseline up to 6 months

Time to any increase in Conn score (mental state grade) was computed as the number of days from the first dose of study drug to the initial occurrence of an increase from baseline in Conn score. Conn score range: Grade 0 (no behavioral abnormality) to Grade 4 (coma; unable to test mental state). Participants who discontinued prior to experiencing an increase in Conn score and prior to completion of the 6-month treatment period were censored at the time of discontinuation. The number of events of the initial occurrence of an increase from baseline in Conn score during the treatment interval is

0 to <28 Days
GroupValue95% CI
Rifaximin17
Placebo26
28 to <56 Days
GroupValue95% CI
Rifaximin5
Placebo21
56 to <84 Days
GroupValue95% CI
Rifaximin9
Placebo15
84 to <140 Days
GroupValue95% CI
Rifaximin5
Placebo10
140 to <168 Days
GroupValue95% CI
Rifaximin0
Placebo5
≥168 Days
GroupValue95% CI
Rifaximin1
Placebo0
Time To Any Increase From Baseline In Asterixis Grade Secondary · Baseline up to 6 months

Time to any increase in asterixis grade was computed as the number of days from the first dose of study drug to the initial occurrence of an increase from baseline in asterixis grade. Asterixis (flapping tremor) was determined with the participant holding both arms and forearms extended with wrists dorsiflexed and fingers open for ≥30 seconds per standard practice. Asterixis grade range: Grade 0 (no abnormal movement) to Grade 4 (almost continuous flapping motions). Participants who discontinued prior to experiencing an increase in asterixis grade and prior to completion of the 6-month treatme

0 to <28 Days
GroupValue95% CI
Rifaximin13
Placebo20
28 to <56 Days
GroupValue95% CI
Rifaximin7
Placebo15
56 to <84 Days
GroupValue95% CI
Rifaximin7
Placebo4
84 to <140 Days
GroupValue95% CI
Rifaximin3
Placebo6
140 to <168 Days
GroupValue95% CI
Rifaximin1
Placebo4
≥168 Days
GroupValue95% CI
Rifaximin1
Placebo1
Mean Change From Baseline In Fatigue Domain Score On The CLDQ At End Of Treatment Secondary · Baseline, 6 months (End Of Treatment)

The 29-item Chronic Liver Disease Questionnaire (CLDQ) questionnaire consists of the following domains: fatigue, activity, emotional function, abdominal symptoms, systemic symptoms, and worry. Participants ranked their level of fatigue by using a 7-point scale from the worst response (1, high degree of fatigue) to the best response (7, minimal fatigue).

Baseline
GroupValue95% CI
Rifaximin3.28± 1.326
Placebo3.34± 1.406
Change from Baseline
GroupValue95% CI
Rifaximin0.30± 1.262
Placebo0.11± 1.319
Mean Change From Baseline In Venous Ammonia Concentration At End Of Treatment Secondary · Baseline, Month 6 (End Of Treatment)

Venous blood samples (10 mL) were collected at Baseline/Randomization (Day 0) and Days 28, 84, and 168. Baseline value was the last available value prior to first dose of study drug, and end of treatment value was the last available post-baseline value during the treatment period.

Baseline
GroupValue95% CI
Rifaximin87.9± 47.76
Placebo92.1± 55.24
Change from Baseline
GroupValue95% CI
Rifaximin-5.7± 46.77
Placebo-1.2± 60.98

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to 6.5 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Rifaximin
Serious: 51/140 (36%)
Deaths:
Placebo
Serious: 63/159 (40%)
Deaths:

Serious adverse events (84 terms)

ReactionSystemRifaximinPlacebo
Hepatic encephalopathyNervous system disorders
Hepatic cirrhosisHepatobiliary disorders
AscitesGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
Oesophageal varices haemorrhageGastrointestinal disorders
PneumoniaInfections and infestations
Renal failure acuteRenal and urinary disorders
Gastrointestinal haemorrhageGastrointestinal disorders
VomitingGastrointestinal disorders
Generalised oedemaGeneral disorders
CellulitisInfections and infestations
Peritonitis bacterialInfections and infestations
Atrial fibrillationCardiac disorders
Cardiac failure congestiveCardiac disorders
Abdominal painGastrointestinal disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
Clostridium colitisInfections and infestations
SepsisInfections and infestations
Urinary tract infectionInfections and infestations
HyperkalaemiaMetabolism and nutrition disorders
Hepatic neoplasm malignantNeoplasms benign, malignant and unspecified (incl cysts and polyps)
SyncopeNervous system disorders
Renal failureRenal and urinary disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
Other adverse events (27 terms — click to expand)

ReactionSystemRifaximinPlacebo
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Oedema peripheralGeneral disorders
FatigueGeneral disorders
DizzinessNervous system disorders
HeadacheNervous system disorders
Hepatic encephalopathyNervous system disorders
AscitesGastrointestinal disorders
VomitingGastrointestinal disorders
Urinary tract infectionInfections and infestations
Abdominal painGastrointestinal disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders
Abdominal distensionGastrointestinal disorders
AstheniaGeneral disorders
InsomniaPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders
NasopharyngitisInfections and infestations
Back painMusculoskeletal and connective tissue disorders
DepressionPsychiatric disorders
ConstipationGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
AnaemiaBlood and lymphatic system disorders
RashSkin and subcutaneous tissue disorders

Most-reported serious reactions: Hepatic encephalopathy, Hepatic cirrhosis, Ascites, Anaemia, Oesophageal varices haemorrhage, Pneumonia, Renal failure acute, Gastrointestinal haemorrhage.

Data from ClinicalTrials.gov NCT00298038 adverse events section.

Sponsor's own description

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

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Rifaximin treatment in hepatic encephalopathy.
    Bass NM, Mullen KD, Sanyal A, Poordad F, et al · · 2010 · cited 834× · PMID 20335583 · DOI 10.1056/nejmoa0907893
  2. Prolonged remission from hepatic encephalopathy with rifaximin: results of a placebo crossover analysis.
    Bajaj JS, Barrett AC, Bortey E, Paterson C, et al · · 2015 · cited 40× · PMID 25339518 · DOI 10.1111/apt.12993
  3. Antibiotic prophylaxis to prevent spontaneous bacterial peritonitis in people with liver cirrhosis: a network meta-analysis.
    Komolafe O, Roberts D, Freeman SC, Wilson P, et al · · 2020 · cited 30× · PMID 31978256 · DOI 10.1002/14651858.cd013125.pub2
  4. Rifaximin has the potential to prevent complications of cirrhosis.
    Flamm SL, Mullen KD, Heimanson Z, Sanyal AJ. · · 2018 · cited 27× · PMID 30283499 · DOI 10.1177/1756284818800307
  5. Rifaximin plus lactulose versus lactulose alone for reducing the risk of HE recurrence.
    Sanyal AJ, Kowdley KV, Reau NS, Pyrsopoulos NT, et al · · 2024 · cited 13× · PMID 38727685 · DOI 10.1097/hc9.0000000000000436
  6. The Interplay of Cross-Organ Immune Regulation in Inflammation and Cancer.
    Dou J, Jiang J, Xue Y, Jiang X, et al · · 2025 · cited 2× · PMID 40529611 · DOI 10.1002/mco2.70249

Verify or expand the search:

Other trials of Rifaximin

Trials testing the same drug.

Other recruiting trials for Hepatic Encephalopathy

Currently open trials in the same condition.

Other Bausch Health Americas, Inc. trials

Trials by the same sponsor.

Verify against primary sources

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00298038.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing