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

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

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

Study Overview

• Status: Completed
• Conditions: Hepatic Encephalopathy
• Intervention / Treatment: Drug: Lactulose; Drug: L-ornithine L-aspartate; Drug: Rifaximin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 4

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 06726
    • Hospital General de Mexico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.
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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of adverse effects	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.	7 days

Collaborators and Investigators

• Sponsor: Hospital General de Mexico

Publications and helpful links

General Publications

• Higuera-de-la-Tijera F, Servin-Caamano AI, Salas-Gordillo F, Perez-Hernandez JL, Abdo-Francis JM, Camacho-Aguilera J, Alla SN, Jimenez-Ponce F. Primary Prophylaxis to Prevent the Development of Hepatic Encephalopathy in Cirrhotic Patients with Acute Variceal Bleeding. Can J Gastroenterol Hepatol. 2018 Jul 10;2018:3015891. doi: 10.1155/2018/3015891. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: June 4, 2014
• First Submitted That Met QC Criteria: June 4, 2014
• First Posted (Estimate): June 6, 2014

Study Record Updates

• Last Update Posted (Actual): May 22, 2018
• Last Update Submitted That Met QC Criteria: May 19, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Cirrhosis; Hepatic Encephalopathy; Acute Variceal Bleeding
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hemorrhage; Hepatic Encephalopathy; Brain Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Excitatory Amino Acid Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Excitatory Amino Acid Agonists; Rifaximin; Lactulose; N-Methylaspartate
• Other Study ID Numbers: DI/14/107/03/028