Comparing Nifuroxazide Plus Lactulose With Lactulose Alone in the Treatment of Hepatic Encephalopathy

Hepatic Encephalopathy Clinical Trial

Official title:

A Randomized Controlled Trial Comparing Nifuroxazide Plus Lactulose With Lactulose Alone in the Treatment of Hepatic Encephalopathy in Egyptian Patients With Liver Cirrhosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05754996
• Other study ID #: CL (3202)
• Status: Recruiting
• Phase: Phase 3
• Start date: March 12, 2023
• Est. completion date: December 2024

Study information

• Verified date: May 2024
• Source: Cairo University
• Contact: Mennat Allah S. Emam
• Phone: 01007906781
• Email: mennatallah.elmlegy[@]fue.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 102
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain Diseases
• Hepatic Encephalopathy

Intervention

Drug:
• Nifuroxazide
Nifuroxazide dosing : 200 mg capsule four times daily
• Lactulose
Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools
• Rifaximin 550Mg Tab
Rifaximin 550 MG twice daily

Locations

Country	Name	City	State
Egypt	National Hepatology and Tropical Medicine Research Institute (NHTMRI)	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Cairo University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	The time for complete reversal of HE		7 days
Primary	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	Length of hospital stay		7 days
Secondary	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
Secondary	Number of patients transferred to ICU		7 days