The Effects of Nitazoxanide in Hepatic Encephalopathy

Study Overview
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Brief Summary
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Evaluating the efficacy and safety of nitazoxanide in comparison to standard treatment in patients with grade II-III hepatic encephalopathy (HE). Also, Evaluating the effect of administering nitazoxanide on the improvement of patient's quality of life.

Detailed Description
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Nitazoxanide (NTZ) is a thiazolide anti-infective with activity against anaerobic bacteria, protozoa and viruses. 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. Based on the excellent safety profile of NTZ, the present pilot study is conducted hopefully to prove the efficacy of nitazoxanide in treating patients experiencing HE grade II-III. Study design:The study is Prospective, Randomized, Controlled, Open-Label, Pilot study. Method: The study will include a total of 36 patients with grade II-III Hepatic Encephalopathy, and an informed consent will be obtained from every patient before being included. All the patients will receive oral lactulose, plus either nitazoxanide, metronidazole or rifaximine. A- All patients will be subjected to the following at baseline: Patient's full history Liver disease staging using Model for End stage Liver Disease (MELD) score Measurement of serum electrolytes (Na+, K+, Ca2+) B- All patients will be subjected to the following at baseline and at the end of treatment: Measuring Blood ammonia level Measuring liver function tests (AST, Total bilirubin, international normalized ratio (INR), Serum albumin, prothrombin time (PT)), serum creatinine and complete blood count (CBC) Assessing severity of Hepatic Encephalopathy using Clinical Hepatic Encephalopathy Staging Scale (CHESS) C- Monitoring tolerability up to 30 days after the last dose D- Assessment of quality of life using Chronic Liver Disease Questionnaire (CLDQ)

Official Title
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The Clinical Effects of Nitazoxanide in Hepatic Encephalopathy Patients: A Pilot Study

Conditions
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Hepatic Encephalopathy

Intervention / Treatment
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* Drug: Nitazoxanide
* Drug: Oral lactulose
* Drug: Metronidazole
* Drug: Rifaximine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult Patients from 18 to 65 years. Patients with grade II-III Hepatic Encephalopathy. Exclusion Criteria: Patients with active GIT bleeding. Patients with major psychiatric illness. Patients receiving benzodiazepines, narcotics, alcohol and marijuana. Patients with compromised renal or biliary functions. Patients known to have AIDS. Patients receiving medications highly bound to plasma proteins eg. Warfarin. Patients with known hypersensitivity to nitazoxanide. Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nitazoxanide group<br>12 patients will receive the following for 7 days: Oral lactulose 500 mg nitazoxanide tablets twice daily | Drug: Nitazoxanide<br>* 500 mg nitazoxanide tablets twice daily<br>Drug: Oral lactulose<br>* Oral lactulose (65%)<br>|
| Active Comparator: Metronidazole group<br>12 patients will receive the following for 7 days: Oral lactulose 250 mg metronidazole tablets every 8 hours | Drug: Oral lactulose<br>* Oral lactulose (65%)<br>Drug: Metronidazole<br>* 250 mg metronidazole tablets every 8 hours<br>|
| Active Comparator: Rifaximine group<br>12 patients will receive the following for 7 days: Oral lactulose Two 200 mg rifaximine tablets every 8 hours | Drug: Oral lactulose<br>* Oral lactulose (65%)<br>Drug: Rifaximine<br>* Two 200 mg rifaximine tablets every 8 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluating the efficacy of nitazoxanide in improving mental status (calculating CHESS score) | evaluating the efficacy by measuring serum ammonia and calculating CHESS score at baseline and at end of treatment | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluating the safety of nitazoxanide (estimation of treatment- related undesirable effects) | Evaluating the safety of nitazoxanide by estimation of treatment- related undesirable effects | 37 days | 
| Effect of nitazoxanide on patient's quality of life (CLDQ score) | Evaluating the effect on quality of life by calculating CLDQ score at baseline and at end of treatment | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic Encephalopathy, Nitazoxanide, Serum ammonia