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

NCT ID: NCT05754996

Last Updated: 2025-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-12
• Study Completion Date: 2025-07-29

Brief 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

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Nifuroxazide

Intervention Type: DRUG

Nifuroxazide dosing : 200 mg capsule four times daily

Lactulose

Intervention Type: DRUG

Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools

Rifaximin 550Mg Tab

Intervention Type: DRUG

Rifaximin 550 MG twice daily

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

Group Type: ACTIVE_COMPARATOR

Lactulose

Intervention Type: DRUG

Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools

Rifaximin 550Mg Tab

Intervention Type: DRUG

Rifaximin 550 MG twice daily

Interventions

Nifuroxazide

Nifuroxazide dosing : 200 mg capsule four times daily

Intervention Type: DRUG

Lactulose

Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools

Intervention Type: DRUG

Rifaximin 550Mg Tab

Rifaximin 550 MG twice daily

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cairo University

OTHER

Sponsor Role: lead

Responsible Party

Mennat Allah Saeid Emam

Teaching assistant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mennat Allah S. Emam

Role: PRINCIPAL_INVESTIGATOR

Cairo University

Locations

National Hepatology and Tropical Medicine Research Institute (NHTMRI)

Cairo, , Egypt

Countries

Egypt

Other Identifiers

CL (3202)

Identifier Type: -

Identifier Source: org_study_id