A Trial for Comparing Rifaximin, Probiotic and L-ornithine- L Aspartate With Lactulose in Overt Hepatic Encephalopathy.

NCT07037394 | Completed Phase 4

• 1 other identifier: 187-2023-/PHEC
• Study Type: interventional
• Target: 252
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this trial is to learn if drugs in group A, B, C and D works to treat reversal of grades in people with overt hepatic encephalopathy. It will also provide information regarding safety of drugs in group A, B, C and D. The main question it aim to answer is: Which study group is better in treating people of overt hepatic encephalopathy. Researchers will compare experimental group B (rifaximin + lactulose), group C (probiotics + lactulose) and group D (LOLA (L-Ornithine L-Aspartate) + lactulose) to control group A lactulose alone in the reversal of grades for people of hepatic encephalopathy. Participants will: Take drug from time of participation in the trial till the end of treatment (day 5) and grade reversal will be observed.

Conditions

Overt Hepatic Encephalopathy

Keywords

Hepatic Insufficiency; Liver Cirrhosis; Rifaximin; West Haven Criteria; Grade Reversal; Lactulose; Liver Diseases

Outcome Measures

Primary Outcomes (1)

• Number of participants of overt hepatic encephalopathy are treated by observing reversal in grades by using West Haven Criteria.

  To compare the efficacy of group B (rifaximin + lactulose), group C (probiotics + lactulose) and group D (LOLA (L-Ornithine L-Aspartate) + lactulose) with group A (lactulose) as controlled group for the treatment of overt hepatic encephalopathy, grade reversal is examined from the time of participation in the trial till the end of treatment (day 5) according to West Heaven Criteria. The West Haven criteria are a widely used system for classifying the severity of hepatic encephalopathy. It grades the condition from Grade 0 (minimal or no symptoms) to Grade 4 (coma) based on the patient's level of consciousness, intellectual function, and behavior.

  From the time of enrollment till the end of treatment (day 5) in the trial.

Secondary Outcomes (3)

• Time of recovery from encephalopathy (Days)

  Time of participation in the study assessed up to 5 days.

• Liver disease severity

  time of participation in the trial till the end of treatment (day 5)

• length of hospital days

  time of participation in the study till the patient is discharged or died or till 28 days whichever occur earlier.

Study Arms (4)

Group A (Lactulose)

ACTIVE COMPARATOR

Participant will receive lactulose syrup (120ml), 30ml (three times a day) TDS orally or by nasogastric tube (NG) for 5 days.

Drug: Lactulose

Group B (Rifaximin + lactulose)

EXPERIMENTAL

Participant will receive Rifaximin tablet 550mg (twice daily) BID with lactulose syrup 30ml (three times a day) TDS orally or by nasogastric tube (NG) for 5 days

Drug: Rifaximin plus lactulose

Group C (Probiotic + lactulose)

EXPERIMENTAL

Participant will receive Probiotic sachet 2g (twice daily) BID with lactulose syrup 30ml (three times a day) TDS orally or by nasogastric tube (NG) for 5 days

Drug: Probiotic plus lactulose

Group D ( (L-Ornithine L- Aspartate) LOLA + Lactulose)

EXPERIMENTAL

Group D: LOLA (L-Ornithine L- Aspartate) concentrate for infusion (5g/10ml = 5g LOLA in 10ml clear solution) + lactulose. Dose: 4 ampoules (40ml) of LOLA 20g of drug diluted in 460ml of 5% dextrose was administered as an intravenous infusion at a rate of 21ml /hour (over 24 hours for 5 days) with lactulose syrup 30ml (three times a day) TDS orally or by nasogastric tube (NG)

Drug: L-ornithine-L-aspartate plus latulose

Interventions

Probiotic plus lactulose DRUG

Probiotic and lactulose will be administered per the dose and schedule specified in the arms.

Also known as: Ecotec plus Duphalac

Group C (Probiotic + lactulose)

Rifaximin plus lactulose DRUG

Rifaximin and lactulose will be administered per the dose and schedule specified in the arms.

Also known as: Rifaxa plus Duphalac

Group B (Rifaximin + lactulose)

L-ornithine-L-aspartate plus latulose DRUG

LOLA and lactulose will be administered per the dose and schedule specified in the arms.

Also known as: Levijon concentrate for infusion plus Duphalac

Group D ( (L-Ornithine L- Aspartate) LOLA + Lactulose)

Lactulose DRUG

Lactulose will be administered per the dose and schedule specified in the arms.

Also known as: Duphalac

Group A (Lactulose)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Both male and female participants with age \>18 to \<80 years old at the time of consent.
• Patients with decompensated chronic liver disease (DCLD) confirmed by ultrasound, endoscopy or blood tests associated with overt hepatic encephalopathy grade II-IV according to West Haven Criteria (WHC) will be included.
• Patients who are unable to talk, their informed consent will be collected from first degree relative and/or legally authorized representative (LAR).
• The subject/LAR has signed the consent/assent form authorized by the ethics committee, is willing to follow the treatment protocol, and has been informed of the purpose of the study.

You may not qualify if:

• Participants with age ≤18 years old and ≥ 80 years old and those with grade1covert hepatic encephalopathy according to West Haven Criteria.
• Patients with comorbidities including ventricular dysfunction and pulmonary edema or neurodegenerative disease (Epilepsy, Parkinson and Drug intoxication), hepatocellular carcinoma (HCC) and with major psychiatric illness (Schizophrenia).
• Patients with presenting complaint of diarrhea will be excluded.
• Recent or current use of sedatives or antidepressants and those who are suffering from encephalitis (viral or bacterial), Wernicke and uremic encephalopathy, stroke or brain tumor will not be included.
• The participant is already participating in another drug trial.
• Pregnant women will not be included.
• Subjects suffering from terminal cancers or HIV-AIDS.
• Participants hypersensitive to lactulose, rifaximin, LOLA and probiotics or any of its excipients will be excluded.

Sponsors & Collaborators

• Qurratul Ain Jamil: lead

Study Sites (1)

Bahawal Victoria Hospital

Bahawalpur, Punjab Province, 63100, Pakistan

Location

Related Publications (1)

• Shahbaz A, Jamil Q, Iqbal SM, Jamil MN, Khan JA, Aufy M. Comparison of efficacy of rifaximin, probiotics and L-ornithine L-aspartate in overt hepatic encephalopathy: a randomized, phase IV, lactulose controlled clinical trial. Trials. 2025 Nov 21;26(1):534. doi: 10.1186/s13063-025-09173-2.

  PMID: 41272855 DERIVED

MeSH Terms

Conditions

Hepatic Insufficiency; Liver Cirrhosis; Liver Diseases

Interventions

Probiotics; Lactulose; Rifaximin; ornithylaspartate

Condition Hierarchy (Ancestors)

Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• QurratulAin Jamil, PhD

  The Islami University of Bahawalpur

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor, Department of Pharmacy Practice, Faculty of Pharmacy, The Islamia University of Bahawalpur

Model Details: A parallel study design involves assigning participants to different treatment groups, with each group receiving a distinct intervention or treatment simultaneously.

Study Record Dates

• First Submitted: June 9, 2025
• First Posted: June 25, 2025
• Study Start: December 2, 2024
• Primary Completion: April 21, 2025
• Study Completion: April 30, 2025
• Last Updated: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)