Hepatic Encephalopathy
Conditions
Keywords
Clinical Hepatic Encephalopathy Staging Scale, Hepatic encephalopathy, Nifuroxazide
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.
Interventions
DRUGNifuroxazide
Nifuroxazide dosing : 200 mg capsule four times daily
DRUGLactulose
Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools
Rifaximin 550 MG twice daily
Sponsors
Cairo University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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..
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Number of patients transferred to ICU | 7 days | — |
Countries
Egypt
Outcome results
None listed