Hepatic EncephalopathyPhase 3NCT05754996
Efficacy and Safety of Nifuroxazide in the Treatment of Hepatic Encephalopathy in Egyptian Patients With Liver Cirrhosis
A Phase 3 study testing Nifuroxazide, Lactulose and Rifaximin 550Mg Tab in people with Hepatic Encephalopathy, run by Cairo University at 1 site in Egypt.
Trial summary
This is a pilot study designed to evaluate the efficacy and safety of nifuroxazide in the treatment of hepatic encephalopathy in patients with grade II-III hepatic encephalopathy Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatic Encephalopathy
- What is being tested?
- Nifuroxazide, Lactulose and Rifaximin 550Mg Tab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteEgypt
- Study dates
- 12 Mar 2023to 29 Jul 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients suffering from liver cirrhosis aging above 18 years who will be admitted to hospital with neuropsychiatric condition suggestive of hepatic encephalopathy (grade II or III) confirmed by their known previous hepatic disease by history, clinical examination and laboratory investigations in the form of hyperammonemia with Model for End-Stage Liver Disease (MELD) score ≤ 25 and patients are able to swallow.
Who cannot join
- Patients with neurological or communication problems.
- Degenerative central nervous system (CNS) disease.
- Any significant psychiatric illness.
- Patients with previous intake of nifuroxazide and rifaximin within the last month.
- Presence of underlying renal impairment (serum creatinine ≥ 2 mg/dL).
- Alcohol consumption within prior 4 weeks.
- Non-hepatic metabolic encephalopathy.
- Anemia with hemoglobin level < 7 g/dL.
Trial locations and contacts
1 site in 1 country.
Egypt1 site
National Hepatology and Tropical Medicine Research Institute (NHTMRI)
Cairo
About this study
This is a pilot study designed to evaluate the efficacy and safety of nifuroxazide in the treatment of hepatic encephalopathy in patients with grade II-III hepatic encephalopathy
Read the detailed description
Hepatic Encephalopathy (HE) is a central nervous system dysfunction caused by liver insufficiency and/or portosystemic shunting, manifesting as a wide spectrum of neurological or psychiatric abnormalities characterized by alteration of cognitive and motor function.
The pathogenesis of hepatic encephalopathy is believed to be due to increased nitrogenous substances, primarily ammonia, in the blood. The treatment goal is to reduce nitrogen load from the GI tract and to improve central nervous system (CNS) status.
Treatment options include lactulose administered orally and non-absorbable antibiotics.
Lactulose is nonabsorbable disaccharides that is currently used as first line agents for the treatment of HE. Its action is thought to be due to Colonic metabolism of lactulose to lactic acid results in acidification of the gut lumen. This favors conversion of ammonium (NH4) to ammonia (NH3) and the passage of ammonia from tissues into the lumen. Gut acidification inhibits ammoniagenic coliform bacteria, leading to increased levels of nonammoniagenic lactobacilli. Lactulose also works as a cathartic, reducing colonic bacterial load.
Nifuroxazide is an oral broad-spectrum nitrofuran antibiotic that is commonly used as an intestinal anti-infective agent. It is active against the majority of intestinal bacteria: Gram-positive (Staphylococcus family) and Gram-negative (Enterobacteriaceae family: Escherichia, Citrobacter, Enterobacter, Klebsiella, Salmonella, Shigella, Yersinia) and is therefore expected to decrease ammonia production and to reverse the symptoms of HE.
- Conditions
- Hepatic Encephalopathy
- Being tested
- Nifuroxazide, Lactulose, Rifaximin 550Mg Tab
- Keywords
- Clinical Hepatic Encephalopathy Staging Scale, Hepatic encephalopathy, Nifuroxazide
- Medical subject headings
- Hepatic Encephalopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NifuroxazideDrug
Nifuroxazide dosing : 200 mg capsule four times daily
LactuloseDrug
Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools
Rifaximin 550Mg TabDrug
Rifaximin 550 MG twice daily
| Study group | Role | What they receive |
|---|---|---|
| lactulose plus Rifaximin plus nifuroxazide | Experimental | Nifuroxazide dosing : 800 mg daily in 4 divided doses for 7 days Lactulose dosing : 30 to 60 mL PO TID to produce 2 to 3 semisoft stools per day.
Rifaximin: 550 mg twice daily Receives: Drug: Nifuroxazide; Drug: Lactulose; Drug: Rifaximin 550Mg Tab |
| Lactulose plus Rifaximin | Active comparator | Lactulose dosing : 30 to 60 mL PO TID to produce 2 to 3 semisoft stools per day.
Rifaximin: 550 mg twice daily Receives: Drug: Lactulose; Drug: Rifaximin 550Mg Tab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients achieving complete reversal of hepatic encephalopathy
Complete reversal is defined as the reversibility of HE from grade 2 or 3 to grade 0 or 1 according to West Haven criteria
Measured: 7 days
The time for complete reversal of HE
Measured: 7 days
Evaluating the efficacy of nifuroxazide in improving mental status by calculating CHESS score
Evaluating the efficacy by measuring serum ammonia at baseline and at end of treatment and calculating (CHESS) score at baseline and at end of treatment.
Measured: 7 days
Secondary outcomes (3)
Length of hospital stay
Measured: 7 days
the rate of adverse events occurring during the treatment
Number of patients who experienced adverse events such as abdominal pain, vomiting, nausea, flatulence, anorexia, rash and headache.
Measured: Maximum 7 days
Number of patients transferred to ICU
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2023
- Study start12 Mar 2023
- Primary completion29 Jul 2025
- Study completion29 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic EncephalopathyStudies of the same condition, open and under way.
- More trials run by Cairo UniversityThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a pilot, open-label, randomized controlled trial. The recruited patients will be randomly allocated in one of two groups: Group I (The study group): patients will receive oral nifuroxazide: 800 mg daily in 4 divided doses for maximum 7 days and lactulose 30 to 60 mL peroral (PO) three times daily (TID) according to bowel movement (to produce 2 to 3 semisoft stools per day) plus rifaximin 550 mg twice daily. Group II (The control group): patients will receive the standard treatment : lactulose 30 to 60 mL PO TID according to bowel movement (to produce 2 to 3 semisoft stools per day) plus rifaximin 550 mg twice daily..
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mennat Allah Saeid Emam, Future University in Egypt
- Investigators
- Mennat Allah S. Emam, Principal investigator, Cairo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05754996
- Sponsor's protocol ID
- CL (3202)
- Status last verified
- Aug 2025
- First submitted
- 23 Feb 2023
- Last updated
- 2 Sep 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Nifuroxazide in the Treatment of Hepatic Encephalopathy in Egyptian Patients With Liver Cirrhosis
- ClinicalTrials.gov ID
- NCT05754996
- Acronym / sponsor ID
- CL (3202)
- Conditions
- Hepatic Encephalopathy
- Keywords
- Clinical Hepatic Encephalopathy Staging Scale, Hepatic encephalopathy, Nifuroxazide
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Study start
- 12 Mar 2023 (actual)
- Primary completion
- 29 Jul 2025 (actual)
- Study completion
- 29 Jul 2025 (actual)
- First posted
- 6 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a pilot study designed to evaluate the efficacy and safety of nifuroxazide in the treatment of hepatic encephalopathy in patients with grade II-III hepatic encephalopathy
Detailed description
Hepatic Encephalopathy (HE) is a central nervous system dysfunction caused by liver insufficiency and/or portosystemic shunting, manifesting as a wide spectrum of neurological or psychiatric abnormalities characterized by alteration of cognitive and motor function.
The pathogenesis of hepatic encephalopathy is believed to be due to increased nitrogenous substances, primarily ammonia, in the blood. The treatment goal is to reduce nitrogen load from the GI tract and to improve central nervous system (CNS) status.
Treatment options include lactulose administered orally and non-absorbable antibiotics.
Lactulose is nonabsorbable disaccharides that is currently used as first line agents for the treatment of HE. Its action is thought to be due to Colonic metabolism of lactulose to lactic acid results in acidification of the gut lumen. This favors conversion of ammonium (NH4) to ammonia (NH3) and the passage of ammonia from tissues into the lumen. Gut acidification inhibits ammoniagenic coliform bacteria, leading to increased levels of nonammoniagenic lactobacilli. Lactulose also works as a cathartic, reducing colonic bacterial load.
Nifuroxazide is an oral broad-spectrum nitrofuran antibiotic that is commonly used as an intestinal anti-infective agent. It is active against the majority of intestinal bacteria: Gram-positive (Staphylococcus family) and Gram-negative (Enterobacteriaceae family: Escherichia, Citrobacter, Enterobacter, Klebsiella, Salmonella, Shigella, Yersinia) and is therefore expected to decrease ammonia production and to reverse the symptoms of HE.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a pilot, open-label, randomized controlled trial. The recruited patients will be randomly allocated in one of two groups: Group I (The study group): patients will receive oral nifuroxazide: 800 mg daily in 4 divided doses for maximum 7 days and lactulose 30 to 60 mL peroral (PO) three times daily (TID) according to bowel movement (to produce 2 to 3 semisoft stools per day) plus rifaximin 550 mg twice daily. Group II (The control group): patients will receive the standard treatment : lactulose 30 to 60 mL PO TID according to bowel movement (to produce 2 to 3 semisoft stools per day) plus rifaximin 550 mg twice daily..
| Arm | Type | Receives |
|---|---|---|
| lactulose plus Rifaximin plus nifuroxazide | Experimental | Drug: Nifuroxazide, Drug: Lactulose, Drug: Rifaximin 550Mg TabNifuroxazide dosing : 800 mg daily in 4 divided doses for 7 days Lactulose dosing : 30 to 60 mL PO TID to produce 2 to 3 semisoft stools per day. Rifaximin: 550 mg twice daily |
| Lactulose plus Rifaximin | Active comparator | Drug: Lactulose, Drug: Rifaximin 550Mg TabLactulose dosing : 30 to 60 mL PO TID to produce 2 to 3 semisoft stools per day. Rifaximin: 550 mg twice daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients suffering from liver cirrhosis aging above 18 years who will be admitted to hospital with neuropsychiatric condition suggestive of hepatic encephalopathy (grade II or III) confirmed by their known previous hepatic disease by history, clinical examination and laboratory investigations in the form of hyperammonemia with Model for End-Stage Liver Disease (MELD) score ≤ 25 and patients are able to swallow.
Key exclusion criteria (8 listed)
- Patients with neurological or communication problems.
- Degenerative central nervous system (CNS) disease.
- Any significant psychiatric illness.
- Patients with previous intake of nifuroxazide and rifaximin within the last month.
- Presence of underlying renal impairment (serum creatinine ≥ 2 mg/dL).
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 |
|---|---|---|
| NifuroxazideNifuroxazide dosing : 200 mg capsule four times daily | Drug | lactulose plus Rifaximin plus nifuroxazide |
| LactuloseLactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools | Drug | Lactulose plus Rifaximin, lactulose plus Rifaximin plus nifuroxazide |
| Rifaximin 550Mg TabRifaximin 550 MG twice daily | Drug | Lactulose plus Rifaximin, lactulose plus Rifaximin plus nifuroxazide |
Primary outcome
Number of patients achieving complete reversal of hepatic encephalopathy
Time frame: 7 days
Complete reversal is defined as the reversibility of HE from grade 2 or 3 to grade 0 or 1 according to West Haven criteria
The time for complete reversal of HE
Time frame: 7 days
Evaluating the efficacy of nifuroxazide in improving mental status by calculating CHESS score
Time frame: 7 days
Evaluating the efficacy by measuring serum ammonia at baseline and at end of treatment and calculating (CHESS) score at baseline and at end of treatment.
3 secondary outcomes
Length of hospital stay
Time frame: 7 days
the rate of adverse events occurring during the treatment
Time frame: Maximum 7 days
Number of patients transferred to ICU
Time frame: 7 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2025.
- 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.
Mennat Allah S. Emam principal investigator
Cairo University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nifuroxazide, Lactulose and Rifaximin 550Mg Tab in people with Hepatic Encephalopathy, run by Cairo University at 1 site in Egypt.
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 1 inclusion and 8 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 2 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of patients achieving complete reversal of hepatic encephalopathy (time frame: 7 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Sep 2025.