Clinical trial NCT05754996: Efficacy and Safety of Nifuroxazide in the Treatment of Hepatic Encephalopathy in Egyptian Patients With Liver Cirrhosis
Official title: Efficacy and Safety of Nifuroxazide in the Treatment of Hepatic Encephalopathy in Egyptian Patients With Liver Cirrhosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hepatic Encephalopathy
Keywords: Clinical Hepatic Encephalopathy Staging Scale
Hepatic encephalopathy
Nifuroxazide
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2023-03-06
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a pilot, open-label, randomized controlled trial.

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) plus rifaximin 550 mg twice daily.

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) plus rifaximin 550 mg twice daily..
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of patients achieving complete reversal of hepatic encephalopathy
timeFrame: 7 days
measure: The time for complete reversal of HE
timeFrame: 7 days
measure: Evaluating the efficacy of nifuroxazide in improving mental status by calculating CHESS score
timeFrame: 7 days
Secondary outcomes:
measure: Length of hospital stay
timeFrame: 7 days
measure: the rate of adverse events occurring during the treatment
timeFrame: Maximum 7 days
measure: Number of patients transferred to ICU
timeFrame: 7 days
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: National Hepatology and Tropical Medicine Research Institute (NHTMRI)
Study officials:
affiliation: Cairo University
name: Mennat Allah S. Emam
role: PRINCIPAL_INVESTIGATOR
References: