Efficacy and Safety of Nifuroxazide in the Treatment of Hepatic Encephalopathy in Egyptian Patients With Liver Cirrhosis

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

Study Overview

• Status: Completed
• Conditions: Hepatic Encephalopathy
• Intervention / Treatment: Drug: Nifuroxazide; Drug: Lactulose; Drug: Rifaximin 550Mg Tab

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 Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • National Hepatology and Tropical Medicine Research Institute (NHTMRI)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lactulose plus Rifaximin plus nifuroxazide; 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	Drug: Nifuroxazide; Nifuroxazide dosing : 200 mg capsule four times daily; Drug: Lactulose; Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools; Drug: Rifaximin 550Mg Tab; Rifaximin 550 MG twice daily
Active Comparator: Lactulose plus Rifaximin; Lactulose dosing : 30 to 60 mL PO TID to produce 2 to 3 semisoft stools per day. Rifaximin: 550 mg twice daily	Drug: Lactulose; Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools; Drug: Rifaximin 550Mg Tab; Rifaximin 550 MG twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	7 days
The time for complete reversal of HE		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.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay		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.	Maximum 7 days
Number of patients transferred to ICU		7 days

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Principal Investigator: Mennat Allah S. Emam, Cairo university

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2023
• Primary Completion (Actual): July 29, 2025
• Study Completion (Actual): July 29, 2025

Study Registration Dates

• First Submitted: February 23, 2023
• First Submitted That Met QC Criteria: February 23, 2023
• First Posted (Actual): March 6, 2023

Study Record Updates

• Last Update Posted (Estimated): September 2, 2025
• Last Update Submitted That Met QC Criteria: August 26, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Hepatic encephalopathy; Clinical Hepatic Encephalopathy Staging Scale; Nifuroxazide
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Digestive System Diseases; Liver Diseases; Brain Diseases, Metabolic; Liver Failure; Hepatic Insufficiency; Nutritional and Metabolic Diseases; Hepatic Encephalopathy; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Carbohydrates; Polycyclic Compounds; Polysaccharides; Heterocyclic Compounds, 4 or More Rings; Disaccharides; Oligosaccharides; Sugars; Rifamycins; Lactams, Macrocyclic; Macrocyclic Compounds; Rifaximin; Lactulose; nifuroxazide
• Other Study ID Numbers: CL (3202)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No