Lactulose, L-ornithine L-aspartate, or Rifaximin Versus Placebo for Preventing Hepatic Encephalopathy in Variceal Bleeding

Study Overview
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Brief Summary
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The aim of this study is to determine whether lactulose, L-ornithine L-aspartate, and rifaximin are effective in the prevention of the development of hepatic encephalopathy in cirrhotic patients with acute variceal bleeding

Official Title
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Comparison of Three Different Schemes:Lactulose, L-ornithine L-aspartate, or Rifaximin, Versus Placebo, as Primary Prophylaxis of the Development of Hepatic Encephalopathy After Acute Variceal Bleeding in Cirrhotic Patients

Conditions
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Hepatic Encephalopathy

Intervention / Treatment
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* Drug: Lactulose
* Drug: L-ornithine L-aspartate
* Drug: Rifaximin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Cirrhotic patients with acute variceal bleeding, without minimal or clinical hepatic encephalopathy according to PHES, CFF and West-Haven criteria Exclusion Criteria: Age under 18 year-old or over 65 year-old, with any other neuropsychiatric disorder or dementia, presence of active bacterial or fungal infections, receiving antibiotics for any cause, previous diagnosis of hepatic encephalopathy and receiving therapy with lactulose, rifaximin, L-ornithine L-aspartate, source of bleeding different from variceal origin, serum creatinine greater than 2.0 mg/dl or with chronic renal failure. Therapy in the previous six months with any of the drugs that will be used in this clinical trial.

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lactulose<br> | Drug: Lactulose<br>* 30 ml by mouth three times daily until melena resolved, then adjusted to dose-response to obtain two to three soft stools. Duration of therapy: 7 days<br>|
| Experimental: L-ornithine L-aspartate<br> | Drug: L-ornithine L-aspartate<br>* 10 grams by intravenous way for 24 hours. Duration of therapy: 7 days<br>|
| Experimental: Rifaximin<br> | Drug: Rifaximin<br>* 2 tablets (400mg) three times daily. Duration of therapy: 7 days<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo (for lactulose) 30ml of dextrose solution by mouth three times daily, for 7 days. Placebo (for L-ornithine L-aspartate) saline solution 500ml by intravenous way for 24 hours, for 7 days. Placebo (for rifaximin) 2 dextrose tablets three times daily for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of clinical hepatic encephalopathy | Determined by West-Haven Criteria | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of minimal hepatic encephalopathy | Determined by psychometric hepatic encephalopathy score (PHES) and critical flicker frequency (CFF) | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic Encephalopathy, Acute Variceal Bleeding, Cirrhosis