Overt Hepatic EncephalopathyPhase 2OHENCT03515044
Rifaximin Soluble Solid Dispersion (SSD) Tablets Plus Lactulose for the Treatment of Overt Hepatic Encephalopathy (OHE)
A Phase 2 study testing 40 mg Rifaximin SSD once daily, 40 mg Rifaximin SSD twice daily and 80 mg Rifaximin SSD once daily in people with Overt Hepatic Encephalopathy, run by Bausch Health Americas, Inc. at 34 sites in United States.
Trial summary
Study to Assess the Efficacy and Safety of Rifaximin Soluble Solid Dispersion (SSD) Tablets Plus Lactulose for the Treatment of Overt Hepatic Encephalopathy (OHE). Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Overt Hepatic Encephalopathy
- What is being tested?
- 40 mg Rifaximin SSD once daily, 40 mg Rifaximin SSD twice daily and 80 mg Rifaximin SSD once daily
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 71 participants
- Where
- 34 sitesUnited States
- Study dates
- 13 Sep 2018to 12 Mar 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female age 18 to 75 years of age (inclusive) at the time of screening.
- Females of childbearing potential, defined as a female who is fertile following menarche, must have a negative serum pregnancy test at screening and agree to use an acceptable method of contraception throughout their participation in the study.
- Note: Female subjects who have been surgically sterilized (e.g., hysterectomy or bilateral tubal ligation) or who are postmenopausal (defined as total cessation of menses for > 1 year) will not be considered "female subjects of childbearing potential".
- Subject is hospitalized with liver cirrhosis and/or OHE and has a confirmed diagnosis of OHE at Baseline.
- Subject has a Grade 2 or Grade 3 HE episode according to the HE Grading Instrument (HEGI) following 8 to 12 hours of intravenous (IV) hydration and lactulose treatment.
Who cannot join
- Subject has an uncontrolled major psychiatric disorder including major depression or psychoses as determined by the investigator.
- Subject has been diagnosed with an infection for which they are currently taking oral or parenteral antibiotics, which cannot be discontinued at time of enrollment. Note: Subjects currently taking Rifaximin are not excluded
- Subject shows presence of intestinal obstruction or has inflammatory bowel disease.
- Subject has uncontrolled Type 1 or Type 2 diabetes. Note: Subjects with controlled diabetes may be enrolled if they are on stable doses of oral hypoglycemic drugs for at least 3 months prior to screening, and demonstrate clinically acceptable blood glucose control at Baseline, as determined by the investigator.
- Subject has an active malignancy (exceptions: non-melanoma skin cancers).
Trial locations and contacts
34 sites in 1 country.
34 sites in 1 country
United States34 sites
Bausch Health Site 03
Boston, Massachusetts, 02215
Bausch Health Site 13
Bristol, Connecticut, 06010
Bausch Health Site 36
Brooklyn, New York, 11215
Bausch Health Site 16
Charleston, South Carolina, 29425
Bausch Health Site 05
Chicago, Illinois, 60611
Bausch Health Site 17
Cincinnati, Ohio, 45219
Bausch Health Site 23
Columbus, Ohio, 43210
Bausch Health Site 18
Corona del Mar, California, 92118
Bausch Health Site 22
Dallas, Texas, 75203
Bausch Health Site 35
Dallas, Texas, 75246
Bausch Health Site 31
Dallas, Texas, 75390
Bausch Health Site 07
Detroit, Michigan, 48109
Bausch Health 01
Detroit, Michigan, 48127
Bausch Health Site 02
Houston, Texas, 77001
Bausch Health Site 37
Houston, Texas, 77030
Bausch Health Site 33
Iowa City, Iowa, 52242
Bausch Health Site 15
Los Angeles, California, 90033
Bausch Health Site 19
Los Angeles, California, 90048
Bausch Health Site 08
Miami, Florida, 33136
Bausch Health Site 20
Milwaukee, Wisconsin, 53226
Bausch Health Site 09
New York, New York, 10029
Bausch Health Site 28
New York, New York, 10065
Bausch Health Site 27
Newark, New Jersey, 07102
Bausch Health Site 11
Philadelphia, Pennsylvania, 19104
Bausch Health Site 26
Philadelphia, Pennsylvania, 19107
Bausch Health Site 10
Philadelphia, Pennsylvania, 19141
Bausch Health Site 12
Pittsburgh, Pennsylvania, 15213
Bausch Health Site 30
Richmond, Virginia, 23226
Bausch Health Site 06
Richmond, Virginia, 23249
Bausch Health Site 04
San Francisco, California, 94143
Bausch Health Site 21
Seattle, Washington, 98104
Bausch Health Site 14
Seattle, Washington, 98195
Bausch Health Site 24
St Louis, Missouri, 63104
Bausch Health Site 25
Tupelo, Mississippi, 38801
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study to Assess the Efficacy and Safety of Rifaximin Soluble Solid Dispersion (SSD) Tablets Plus Lactulose for the Treatment of Overt Hepatic Encephalopathy (OHE)
Study to Assess the Efficacy and Safety of Rifaximin Soluble Solid Dispersion (SSD) Tablets Plus Lactulose for the Treatment of Overt Hepatic Encephalopathy (OHE).
Read the detailed description
The primary objective of this study is to assess the efficacy of rifaximin SSD plus lactulose versus placebo plus lactulose for the treatment of overt hepatic encephalopathy (OHE). The secondary objectives of this study are to assess the safety of rifaximin SSD in subjects with OHE and to assess the effects of treatment with rifaximin SSD on key secondary endpoints.
- Conditions
- Overt Hepatic Encephalopathy
- Being tested
- 40 mg Rifaximin SSD once daily, 40 mg Rifaximin SSD twice daily, 80 mg Rifaximin SSD once daily, 80 mg Rifaximin SSD twice daily, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
40 mg Rifaximin SSD once dailyDrug
SSD once daily (QD)
40 mg Rifaximin SSD twice dailyDrug
SSD twice daily (BID)
80 mg Rifaximin SSD once dailyDrug
SSD once daily (QD)
80 mg Rifaximin SSD twice dailyDrug
SSD twice daily (BID)
PlaceboDrug
Administered twice daily (BID)
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 40 mg Rifaximin SSD once daily | Experimental | 40 mg Rifaximin immediate release (IR) rifaximin SSD once daily (QD) and lactulose Receives: Drug: 40 mg Rifaximin SSD once daily |
| Cohort 2 40 mg Rifaximin SSD twice daily | Experimental | 40 mg Rifaximin immediate release (IR) rifaximin SSD twice daily (BID) and lactulose Receives: Drug: 40 mg Rifaximin SSD twice daily |
| Cohort 3 80 mg Rifaximin SSD once daily | Experimental | 80 mg Rifaximin sustained extended release (SER) rifaximin SSD once daily (QD) and lactulose Receives: Drug: 80 mg Rifaximin SSD once daily |
| Cohort 4 80 mg Rifaximin SSD twice daiy | Experimental | 80 mg Rifaximin sustained extended release (SER) rifaximin SSD twice daily (BID) and lactulose Receives: Drug: 80 mg Rifaximin SSD twice daily |
| Cohort 5 Placebo twice daily | Experimental | SSD placebo twice daily (BID) and lactulose Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Overt Hepatic Encephalopathy (OHE) Resolution Determined Using the Hepatic Encephalopathy Grading Instrument (HEGI), Defined as HEGI Score < 2
A participant was considered to have an overt HE episode if at least one of the following applied: (1) Disorientated to time or place or person, (2) Lethargic and has asterixis, (3) Inability to assess the patient due to disorientation to time and place and person; and/or somnolence, and/or coma. Severity of OHE episodes was graded using the HEGI scale, where Grade 1 is no clinical findings of OHE, and Grade 4 is comatose. Higher scores on the scale have higher severity (worse outcome).
Measured: 14 days
Secondary outcomes (2)
Time to Improvement in Hepatic Encephalopathy Grading Instrument (HEGI) Score, Defined as at Least One Grade Decrease (Improvement)
A participant was considered to have an overt HE episode if at least one of the following applied: (1) Disorientated to time or place or person, (2) Lethargic and has asterixis, (3) Inability to assess the patient due to disorientation to time and place and person; and/or somnolence, and/or coma. Severity of OHE episodes was graded using the HEGI scale, where Grade 1 is no clinical findings of OHE, and Grade 4 is comatose. Higher scores on the scale have higher severity (worse outcome).
Measured: 14 days
Time to Hospital Discharge
Time in days until discharge from the hospital
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2018
- Study start13 Sep 2018
- Primary completion12 Mar 2020
- Study completion12 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Overt Hepatic EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bausch Health Americas, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Angela Bulawski, Study director, Bausch Health Americas, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03515044
- Sponsor's protocol ID
- RNHE2041
- Acronym
- OHE
- Status last verified
- Mar 2023
- First submitted
- 12 Apr 2018
- Last updated
- 13 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Bajaj JS, Hassanein TI, Pyrsopoulos NT, Sanyal AJ, Rahimi RS, Heimanson Z, Israel RJ, Rockey DC. Dosing of Rifaximin Soluble Solid Dispersion Tablets in Adults With Cirrhosis: 2 Randomized, Placebo-controlled Trials. Clin Gastroenterol Hepatol. 2023 Mar;21(3):723-731.e9. doi: 10.1016/j.cgh.2022.05.042. Epub 2022 Jun 22.
PubMed 35750249
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study to Assess the Efficacy and Safety of Rifaximin Soluble Solid Dispersion (SSD) Tablets Plus Lactulose for the Treatment of Overt Hepatic Encephalopathy (OHE)
- ClinicalTrials.gov ID
- NCT03515044
- Acronym / sponsor ID
- OHE / RNHE2041
- Conditions
- Overt Hepatic Encephalopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Bausch Health Americas, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Sep 2018 (actual)
- Primary completion
- 12 Mar 2020 (actual)
- Study completion
- 12 Mar 2020 (actual)
- First posted
- 3 May 2018 (actual)
- Results
- Posted 13 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study to Assess the Efficacy and Safety of Rifaximin Soluble Solid Dispersion (SSD) Tablets Plus Lactulose for the Treatment of Overt Hepatic Encephalopathy (OHE).
Detailed description
The primary objective of this study is to assess the efficacy of rifaximin SSD plus lactulose versus placebo plus lactulose for the treatment of overt hepatic encephalopathy (OHE). The secondary objectives of this study are to assess the safety of rifaximin SSD in subjects with OHE and to assess the effects of treatment with rifaximin SSD on key secondary endpoints.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 5
- Model description
- Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 40 mg Rifaximin SSD once daily | Experimental | Drug: 40 mg Rifaximin SSD once daily40 mg Rifaximin immediate release (IR) rifaximin SSD once daily (QD) and lactulose |
| Cohort 2 40 mg Rifaximin SSD twice daily | Experimental | Drug: 40 mg Rifaximin SSD twice daily40 mg Rifaximin immediate release (IR) rifaximin SSD twice daily (BID) and lactulose |
| Cohort 3 80 mg Rifaximin SSD once daily | Experimental | Drug: 80 mg Rifaximin SSD once daily80 mg Rifaximin sustained extended release (SER) rifaximin SSD once daily (QD) and lactulose |
| Cohort 4 80 mg Rifaximin SSD twice daiy | Experimental | Drug: 80 mg Rifaximin SSD twice daily80 mg Rifaximin sustained extended release (SER) rifaximin SSD twice daily (BID) and lactulose |
| Cohort 5 Placebo twice daily | Experimental | Drug: PlaceboSSD placebo twice daily (BID) and lactulose |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female age 18 to 75 years of age (inclusive) at the time of screening.
- Females of childbearing potential, defined as a female who is fertile following menarche, must have a negative serum pregnancy test at screening and agree to use an acceptable method of contraception throughout their participation in the study.
- Note: Female subjects who have been surgically sterilized (e.g., hysterectomy or bilateral tubal ligation) or who are postmenopausal (defined as total cessation of menses for > 1 year) will not be considered "female subjects of childbearing potential".
- Subject is hospitalized with liver cirrhosis and/or OHE and has a confirmed diagnosis of OHE at Baseline.
- Subject has a Grade 2 or Grade 3 HE episode according to the HE Grading Instrument (HEGI) following 8 to 12 hours of intravenous (IV) hydration and lactulose treatment.
Key exclusion criteria (5 listed)
- Subject has an uncontrolled major psychiatric disorder including major depression or psychoses as determined by the investigator.
- Subject has been diagnosed with an infection for which they are currently taking oral or parenteral antibiotics, which cannot be discontinued at time of enrollment. Note: Subjects currently taking Rifaximin are not excluded
- Subject shows presence of intestinal obstruction or has inflammatory bowel disease.
- Subject has uncontrolled Type 1 or Type 2 diabetes. Note: Subjects with controlled diabetes may be enrolled if they are on stable doses of oral hypoglycemic drugs for at least 3 months prior to screening, and demonstrate clinically acceptable blood glucose control at Baseline, as determined by the investigator.
- Subject has an active malignancy (exceptions: non-melanoma skin cancers).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 40 mg Rifaximin SSD once dailySSD once daily (QD) | Drug | Cohort 1 40 mg Rifaximin SSD once daily |
| 40 mg Rifaximin SSD twice dailySSD twice daily (BID) | Drug | Cohort 2 40 mg Rifaximin SSD twice daily |
| 80 mg Rifaximin SSD once dailySSD once daily (QD) | Drug | Cohort 3 80 mg Rifaximin SSD once daily |
| 80 mg Rifaximin SSD twice dailySSD twice daily (BID) | Drug | Cohort 4 80 mg Rifaximin SSD twice daiy |
| PlaceboAdministered twice daily (BID) | Drug | Cohort 5 Placebo twice daily |
Primary outcome
Time to Overt Hepatic Encephalopathy (OHE) Resolution Determined Using the Hepatic Encephalopathy Grading Instrument (HEGI), Defined as HEGI Score < 2
Time frame: 14 days
A participant was considered to have an overt HE episode if at least one of the following applied: (1) Disorientated to time or place or person, (2) Lethargic and has asterixis, (3) Inability to assess the patient due to disorientation to time and place and person; and/or somnolence, and/or coma. Severity of OHE episodes was graded using the HEGI scale, where Grade 1 is no clinical findings of OHE, and Grade 4 is comatose. Higher scores on the scale have higher severity (worse outcome).
2 secondary outcomes
Time to Improvement in Hepatic Encephalopathy Grading Instrument (HEGI) Score, Defined as at Least One Grade Decrease (Improvement)
Time frame: 14 days
Time to Hospital Discharge
Time frame: 14 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35750249Bajaj JS, Hassanein TI, Pyrsopoulos NT, Sanyal AJ, Rahimi RS, Heimanson Z, Israel RJ, Rockey DC. Dosing of Rifaximin Soluble Solid Dispersion Tablets in Adults With Cirrhosis: 2 Randomized, Placebo-controlled Trials. Clin Gastroenterol Hepatol. 2023 Mar;21(3):723-731.e9. doi: 10.1016/j.cgh.2022.05.042. Epub 2022 Jun 22.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angela Bulawski study director
Bausch Health Americas, Inc.
34 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 40 mg Rifaximin SSD once daily, 40 mg Rifaximin SSD twice daily and 80 mg Rifaximin SSD once daily in people with Overt Hepatic Encephalopathy, run by Bausch Health Americas, Inc. at 34 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Overt Hepatic Encephalopathy (OHE) Resolution Determined Using the Hepatic Encephalopathy Grading Instrument (HEGI), Defined as HEGI Score < 2 (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03515044, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2023.