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

Cairo University (CU)

Status and phase: Enrolling; Phase 3

Conditions: Hepatic Encephalopathy

Treatments: Drug: Nifuroxazide; Drug: Rifaximin 550Mg Tab; Drug: Lactulose

Study type: Interventional

Funder types: Other

Identifiers

NCT05754996

CL (3202)

Details and patient eligibility

About

Evaluating the efficacy and safety of the efficacy and safety of nifuroxazide in the treatment of hepatic encephalopathy in patients with grade II-III hepatic encephalopathy

Full 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.

Enrollment: 102 estimated patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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102 participants in 2 patient groups

lactulose plus Rifaximin plus nifuroxazide

Experimental group

Description:

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

Treatment:

Drug: Rifaximin 550Mg Tab

Drug: Lactulose

Drug: Nifuroxazide

Lactulose plus Rifaximin

Active Comparator group

Description:

Lactulose dosing : 30 to 60 mL PO TID to produce 2 to 3 semisoft stools per day. Rifaximin: 550 mg twice daily

Treatment:

Drug: Rifaximin 550Mg Tab

Drug: Lactulose