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Nitazoxanide Plus Lactulose Versus Lactulose Alone Treatment of Hepatic Encephalopathy

Phase 2
Conditions
Encephalopathy, Hepatic
Interventions
Registration Number
NCT02464124
Lead Sponsor
Sherief Abd-Elsalam
Brief Summary

Hepatic encephalopathy (HE) is a reversible neuropsychiatric syndrome associated with chronic and acute liver dysfunction. It is characterized by cognitive and motor deficits of varying severity.

Treatment options include lactulose administered orally or by nasogastric tube or enema, non-absorbable antibiotics, and protein-restricted diets.

Nitazoxanide is an oral agent indicated for the treatment of infectious diarrhea caused by Crytpsporidiumparvum and Giardia lamblia. Basu and colleagues presented a pilot prospective study at the 2008 American Association for the Study of Liver Diseases meeting showing clinical improvement in HE among cirrhotic patients who received nitazoxanide and lactulose.

Detailed Description

Hepatic encephalopathy (HE) is a reversible neuropsychiatric syndrome associated with chronic and acute liver dysfunction. It is characterized by cognitive and motor deficits of varying severity.

Hepatic encephalopathy is caused by accumulation of nitrogenous substances, primarily ammonia, in the blood. In advanced stages it is referred to as hepatic coma which may be preceded by seizures. 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 or by nasogastric tube or enema, non-absorbable antibiotics, and protein-restricted diets.

Lactulose is nonabsorbable disaccharides that are currently used as first line agents for the treatment of HE. Its action is thought to beconversion to lactic acid and acetic acid resulting in acidification of the gut lumen. This favors conversion of ammonia (NH3) to ammonium (NH4+), which is relatively membrane impermeable, and inhibits ammoniagenic coliform bacteria.

Nitazoxanide is an oral agent indicated for the treatment of infectious diarrhea caused by Crytpsporidiumparvum and Giardia lamblia. Basu and colleagues presented a pilot prospective study at the 2008 American Association for the Study of Liver Diseases meeting showing clinical improvement in HE among cirrhotic patients who received nitazoxanide and lactulose.

Mantry and colleagues showed that the number of hospitalizations and the duration of hospital stays were shortened for patients receiving combination therapy compared with those receiving lactulose monotherapy.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
120
Inclusion Criteria

Age 18-70 years

Cirrhosis, defined by a combination of any of the following:

  • Laboratory findings
  • Endoscopic results
  • Ultrasound
  • Histology Overt hepatic encephalopathy
Exclusion Criteria
  • • Creatinine>1.5 mg/dl

    • Alcohol use within prior 4 weeks
    • Non-hepatic metabolic encephalopathy
    • Hepatocellular carcinoma
    • Degenerative CNS disease
    • Any significant psychiatric illness or other medical comorbidity

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
lactulose plus nitazoxanideLactulose* Nitazoxanide dosing: 500 mg tablets twice daily * Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools per day
lactulose plus nitazoxanideNitazoxanide* Nitazoxanide dosing: 500 mg tablets twice daily * Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools per day
Lactulose aloneLactuloseLactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools per day
Primary Outcome Measures
NameTimeMethod
Number of patients with total reversal of hepatic encephalopathy6 months
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Tanta university - faculty of medicine

🇪🇬

Tanta, Elgharbia, Egypt

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