Nitazoxanide Plus Lactulose Versus Lactulose Alone Treatment of Hepatic Encephalopathy

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Double-blind, Controlled Trial Comparing Nitazoxanide Plus Lactulose With Lactulose Alone Treatment of Overt Hepatic Encephalopathy

Conditions
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Encephalopathy, Hepatic

Intervention / Treatment
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* Drug: Nitazoxanide
* Drug: Lactulose


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lactulose plus nitazoxanide<br>Nitazoxanide dosing: 500 mg tablets twice daily Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools per day | Drug: Nitazoxanide<br>* • Nitazoxanide dosing: 500 mg tablets twice daily<br>* Other names: Alenia, Nitclean, Parazoxanide;Drug: Lactulose<br>* • Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools per day<br>* Other names: Laxolac, Duphlac;|
| Active Comparator: Lactulose alone<br>Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools per day | Drug: Lactulose<br>* • Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools per day<br>* Other names: Laxolac, Duphlac;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with total reversal of hepatic encephalopathy |  | 6 months |