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Nitazoxanide Plus Lactulose Versus Lactulose Alone Treatment of Hepatic Encephalopathy

Sponsor
Sherief Abd-Elsalam (Other)
Overall Status
Unknown status
CT.gov ID
NCT02464124
Collaborator
Tanta University (Other)
120
Enrollment
1
Location
2
Arms
23
Anticipated Duration (Months)
5.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Controlled Trial Comparing Nitazoxanide Plus Lactulose With Lactulose Alone Treatment of Overt Hepatic Encephalopathy
Actual Study Start Date :
Jan 1, 2016
Anticipated Primary Completion Date :
Dec 1, 2017
Anticipated Study Completion Date :
Dec 1, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: lactulose plus nitazoxanide

Nitazoxanide dosing: 500 mg tablets twice daily Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools per day

Drug: Nitazoxanide
• Nitazoxanide dosing: 500 mg tablets twice daily
Other Names:
  • Alenia, Nitclean, Parazoxanide

    • Drug: Lactulose
    • Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools per day
    Other Names:
  • Laxolac, Duphlac

    		•
    Active Comparator: Lactulose alone

    Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools per day

    Drug: Lactulose
    • Lactulose dosing: 30-60 mL PO TID with goal 2-3 semisoft stools per day
    Other Names:
  • Laxolac, Duphlac

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of patients with total reversal of hepatic encephalopathy [6 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Tanta university - faculty of medicine Tanta Elgharbia Egypt

    Sponsors and Collaborators

    • Sherief Abd-Elsalam
    • Tanta University

    Investigators

    • Principal Investigator: Asem Elfert, Prof, hepatology dept-Tanta
    • Study Director: Sherief Abd-Elsalam, lecturer, hepatology dept-Tanta
    • Study Chair: Samah Soliman, lecturer, hepatology dept-Tanta
    • Study Chair: Walaa elkhalawany, lecturer, hepatology dept-Tanta
    • Study Chair: Rehab elsheshtawi, lecturer, hepatology dept-Tanta
    • Study Chair: Mennat-Allah Elsawaf, lecturer, hepatology dept-Tanta

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sherief Abd-Elsalam, sponsor investigator, Tanta University
    ClinicalTrials.gov Identifier:
    NCT02464124
    Other Study ID Numbers:
    • Hepatic encephalopathy
    First Posted:
    Jun 8, 2015
    Last Update Posted:
    Aug 21, 2017
    Last Verified:
    Aug 1, 2017
    Additional relevant MeSH terms:
    Hepatic Encephalopathy
    Brain Diseases
    Nitazoxanide
    Lactulose

    Study Results

    No Results Posted as of Aug 21, 2017