The Effects of Nitazoxanide in Hepatic Encephalopathy

Phase 2

• Conditions: Hepatic Encephalopathy
• Interventions: Drug: Nitazoxanide; Drug: Oral lactulose; Drug: Metronidazole; Drug: Rifaximine

• Registration Number: NCT02334163
• Lead Sponsor: Ain Shams University

Brief Summary

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

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)

Study Timeline

• Study Start: 2014-12
• Status Verified: 2015-01
• Study First Submitted: 2015-01-06
• Study First Submitted QC: 2015-01-07
• Last Update Submitted: 2015-01-07
• Study First Posted: 2015-01-08
• Last Update Posted: 2015-01-08
• Primary Completion: 2015-02
• Study Completion: 2015-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 36

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nitazoxanide group	Nitazoxanide	12 patients will receive the following for 7 days: * Oral lactulose * 500 mg nitazoxanide tablets twice daily
Metronidazole group	Oral lactulose	12 patients will receive the following for 7 days: * Oral lactulose * 250 mg metronidazole tablets every 8 hours
Nitazoxanide group	Oral lactulose	12 patients will receive the following for 7 days: * Oral lactulose * 500 mg nitazoxanide tablets twice daily
Rifaximine group	Oral lactulose	12 patients will receive the following for 7 days: * Oral lactulose * Two 200 mg rifaximine tablets every 8 hours
Metronidazole group	Metronidazole	12 patients will receive the following for 7 days: * Oral lactulose * 250 mg metronidazole tablets every 8 hours
Rifaximine group	Rifaximine	12 patients will receive the following for 7 days: * Oral lactulose * Two 200 mg rifaximine tablets every 8 hours

Primary Outcome Measures

Name	Time	Method
Evaluating the efficacy of nitazoxanide in improving mental status (calculating CHESS score)	7 days	evaluating the efficacy by measuring serum ammonia and calculating CHESS score at baseline and at end of treatment

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Faculty of medicine, Ain Shams University; 🇪🇬 Cairo, Egypt