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

Sponsor

Cairo University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05754996

Collaborator

(none)

102

Enrollment

Location

Arms

Anticipated Duration (Months)

6.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Evaluating the efficacy and safety of the efficacy and safety of nifuroxazide in combination with lactulose in comparison to lactulose alone in the treatment of hepatic encephalopathy in patients with grade II-III hepatic encephalopathy

Condition or Disease	Intervention/Treatment	Phase
Hepatic Encephalopathy	Drug: Nifuroxazide Drug: Lactulose	Phase 3

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

Study Type:

Interventional

Anticipated Enrollment :

102 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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). 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).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). 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).

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: lactulose 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.	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
Active Comparator: Lactulose alone Lactulose dosing : 30 to 60 mL PO TID to produce 2 to 3 semisoft stools per day.	Drug: Lactulose Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools

Arm

Intervention/Treatment

Experimental: lactulose 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.

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

Active Comparator: Lactulose alone

Lactulose dosing : 30 to 60 mL PO TID to produce 2 to 3 semisoft stools per day.

Drug: Lactulose

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

Outcome Measures

Primary Outcome Measures

Number of patients achieving complete reversal of hepatic encephalopathy [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 [7 days]
Evaluating the efficacy of nifuroxazide in improving mental status by calculating CHESS score [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.

Secondary Outcome Measures

Length of hospital stay [7 days]
the rate of adverse events occurring during the treatment [Maximum 7 days]
Number of patients who experienced adverse events such as abdominal pain, vomiting, nausea, flatulence, anorexia, rash and headache.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients suffering from liver cirrhosis aging from 18-64 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.
Anemia with hemoglobin level < 8 g/dL.
Presence of underlying renal impairment (serum creatinine > 1.5 mg/dL).
Alcohol consumption within prior 4 weeks.
Non-hepatic metabolic encephalopathy.