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

Sponsor

Hospital General de Mexico (Other)

Overall Status

Completed

CT.gov ID

NCT02158182

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hepatic Encephalopathy	Drug: Lactulose Drug: L-ornithine L-aspartate Drug: Rifaximin Drug: Placebo	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

88 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Jul 1, 2014

Actual Primary Completion Date :

Jun 1, 2016

Actual Study Completion Date :

Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: lactulose	Drug: Lactulose 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
Experimental: L-ornithine L-aspartate	Drug: L-ornithine L-aspartate 10 grams by intravenous way for 24 hours. Duration of therapy: 7 days
Experimental: Rifaximin	Drug: Rifaximin 2 tablets (400mg) three times daily. Duration of therapy: 7 days
Placebo Comparator: Placebo	Drug: Placebo 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.

Outcome Measures

Primary Outcome Measures

Development of clinical hepatic encephalopathy [7 days]
Determined by West-Haven Criteria

Secondary Outcome Measures

Development of minimal hepatic encephalopathy [7 days]
Determined by psychometric hepatic encephalopathy score (PHES) and critical flicker frequency (CFF)

Other Outcome Measures

Development of adverse effects [7 days]
Side or adverse effect will be defined as an undesirable secondary effect which occurs in addition to the desired therapeutic effect of a drug or medication. Non serious side effect will be defined as an undesirable secondary effect that does not represents a risk for patient´s life or function. Particularly we will addressed: Diarrhea, bloating, nausea, vomiting, elevation of serum creatinine, flatulence, abdominal pain, constipation, headache, dizziness Serious side effect will be defined as an undesirable secondary effect that represents a risk for patient´s life or function. Particularly we will addressed: allergic reactions.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.