Overt Hepatic EncephalopathyPhase 4ARGO-HECNCT07037394
A Trial for Comparing Rifaximin, Probiotic and L-ornithine- L Aspartate With Lactulose in Overt Hepatic Encephalopathy.
A Phase 4 study testing Probiotic plus lactulose, Rifaximin plus lactulose and L-ornithine-L-aspartate plus latulose in people with Overt Hepatic Encephalopathy, run by Qurratul Ain Jamil at 1 site in Pakistan.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Overt Hepatic Encephalopathy
- What is being tested?
- Probiotic plus lactulose, Rifaximin plus lactulose and L-ornithine-L-aspartate plus latulose
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 252 participants
- Where
- 1 sitePakistan
- Study dates
- 2 Dec 2024to 30 Apr 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison of Efficacy of Rifaximin, Probiotics and LOLA (L-Ornithine L-Aspartate) in Overt Hepatic Encephalopathy: A Randomized, Phase-IV, Lactulose Controlled Clinical Trial.
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.
Read more
Participants will:
Take drug from time of participation in the trial till the end of treatment (day 5) and grade reversal will be observed.
Read the detailed description
This clinical trial aim to compare the efficacy of four groups which are group A (lactulose) as controlled group, group B (rifaximin + lactulose), group C (probiotics + lactulose)and group D (LOLA (L-Ornithine L-Aspartate) + lactulose) for treating overt hepatic encephalopathy.
Primary objective: The primary objective of our trial will be to compare the grade reversal in overt hepatic encephalopathy patients from the time of trial participation till the end of trial treatment (day 5) according to West Heaven Criteria in both control and interventional groups.
Secondary objectives:
- To find the length of hospital stay and recovery time (in days) from hepatic encephalopathy in both control and interventional groups.
- Monitoring of Adverse drug reactions in both control and interventional groups.
- To assess the mortality in both control and interventional groups.
This trial is single-centered, parallel, multi-arm, 1:1:1:1 randomized, unblinded, lactulose controlled superiority clinical trial comparing the efficacy of four groups which are group A (lactulose) as controlled group, group B (rifaximin + lactulose), group C (probiotics + lactulose) and group D (LOLA (L-Ornithine L-Aspartate) + lactulose) for the treatment of overt hepatic encephalopathy.
Framework/hypothesis: The experimental group B (rifaximin + lactulose), group C (probiotics + lactulose) and group D (LOLA (L-Ornithine L-Aspartate) + lactulose) are superior to control group A lactulose alone in the reversal of grades for patients of hepatic encephalopathy.
- Conditions
- Overt Hepatic Encephalopathy
- Being tested
- Probiotic plus lactulose, Rifaximin plus lactulose, L-ornithine-L-aspartate plus latulose, Lactulose
- Keywords
- Hepatic Insufficiency, Liver Cirrhosis, Rifaximin, West Haven Criteria, Grade Reversal, Lactulose, Liver Diseases
- Medical subject headings
- Hepatic Insufficiency, Liver Cirrhosis, Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probiotic plus lactuloseDrug
Also called Ecotec plus Duphalac
Probiotic and lactulose will be administered per the dose and schedule specified in the arms.
Rifaximin plus lactuloseDrug
Also called Rifaxa plus Duphalac
Rifaximin and lactulose will be administered per the dose and schedule specified in the arms.
L-ornithine-L-aspartate plus latuloseDrug
Also called Levijon concentrate for infusion plus Duphalac
LOLA and lactulose will be administered per the dose and schedule specified in the arms.
LactuloseDrug
Also called Duphalac
Lactulose will be administered per the dose and schedule specified in the arms.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: 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 Receives: 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) Receives: Drug: L-ornithine-L-aspartate plus latulose |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 recovery from encephalopathy is defined as the time taken (in days) to recover from grade 2 or above mental state grade to grade 1 or below.
Measured: Time of participation in the study assessed up to 5 days.
Liver disease severity
Severity of liver disease will be evaluated by Child-pug class. The Child-Pugh score is a clinical tool designed to evaluate the severity of chronic liver disease, including conditions like hepatic encephalopathy (HE). It classifies patients into three categories: A, B, and C, reflecting the degree of liver dysfunction. A higher score corresponds to more severe liver disease and a worse prognosis. This scoring system aids in assessing liver damage, predicting patient survival, and informing treatment options, such as the necessity for liver transplantation.
Interpretation:
Child-Pugh Class A: 5-6 points, indicating well-compensated liver disease. Child-Pugh Class B: 7-9 points, indicating moderately impaired liver function. Child-Pugh Class C: 10-15 points, indicating severely compromised liver function and decompensation.
Measured: time of participation in the trial till the end of treatment (day 5)
length of hospital days
To find length of in- hospital stay (days) is defined as the time patient spent in hospital setting until he/she is discharged.
Measured: time of participation in the study till the patient is discharged or died or till 28 days whichever occur earlier.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2025
- Study start2 Dec 2024
- Primary completion21 Apr 2025
- Study completion30 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Overt Hepatic EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A parallel study design involves assigning participants to different treatment groups, with each group receiving a distinct intervention or treatment simultaneously.
- Masking
- None (open label)
- Enrolment
- 252 participants (actual)
Sponsor and investigators
- Lead sponsor
- Qurratul Ain Jamil
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Qurratul Ain Jamil, Islamia University of Bahawalpur
- Investigators
- QurratulAin Jamil, PhD, Principal investigator, The Islami University of Bahawalpur
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07037394
- Sponsor's protocol ID
- 187-2023-/PHEC
- Acronym
- ARGO-HEC
- Status last verified
- Jun 2025
- First submitted
- 9 Jun 2025
- Last updated
- 25 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41272855
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Efficacy of Rifaximin, Probiotics and LOLA (L-Ornithine L-Aspartate) in Overt Hepatic Encephalopathy: A Randomized, Phase-IV, Lactulose Controlled Clinical Trial.
- ClinicalTrials.gov ID
- NCT07037394
- Acronym / sponsor ID
- ARGO-HEC / 187-2023-/PHEC
- Conditions
- Overt Hepatic Encephalopathy
- Keywords
- Hepatic Insufficiency, Liver Cirrhosis, Rifaximin, West Haven Criteria, Grade Reversal, Lactulose, Liver Diseases
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 252 participants (actual)
- Lead sponsor
- Qurratul Ain JamilUniversity, hospital or other
- Study start
- 2 Dec 2024 (actual)
- Primary completion
- 21 Apr 2025 (actual)
- Study completion
- 30 Apr 2025 (actual)
- First posted
- 25 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This clinical trial aim to compare the efficacy of four groups which are group A (lactulose) as controlled group, group B (rifaximin + lactulose), group C (probiotics + lactulose)and group D (LOLA (L-Ornithine L-Aspartate) + lactulose) for treating overt hepatic encephalopathy.
Primary objective: The primary objective of our trial will be to compare the grade reversal in overt hepatic encephalopathy patients from the time of trial participation till the end of trial treatment (day 5) according to West Heaven Criteria in both control and interventional groups.
Secondary objectives:
- To find the length of hospital stay and recovery time (in days) from hepatic encephalopathy in both control and interventional groups.
- Monitoring of Adverse drug reactions in both control and interventional groups.
- To assess the mortality in both control and interventional groups.
This trial is single-centered, parallel, multi-arm, 1:1:1:1 randomized, unblinded, lactulose controlled superiority clinical trial comparing the efficacy of four groups which are group A (lactulose) as controlled group, group B (rifaximin + lactulose), group C (probiotics + lactulose) and group D (LOLA (L-Ornithine L-Aspartate) + lactulose) for the treatment of overt hepatic encephalopathy.
Framework/hypothesis: The experimental group B (rifaximin + lactulose), group C (probiotics + lactulose) and group D (LOLA (L-Ornithine L-Aspartate) + lactulose) are superior to control group A lactulose alone in the reversal of grades for patients of hepatic encephalopathy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- A parallel study design involves assigning participants to different treatment groups, with each group receiving a distinct intervention or treatment simultaneously.
| Arm | Type | Receives |
|---|---|---|
| Group A (Lactulose) | Active comparator | Drug: LactuloseParticipant will receive lactulose syrup (120ml), 30ml (three times a day) TDS orally or by nasogastric tube (NG) for 5 days. |
| Group B (Rifaximin + lactulose) | Experimental | Drug: Rifaximin plus lactuloseParticipant 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 |
| Group C (Probiotic + lactulose) | Experimental | Drug: Probiotic plus lactuloseParticipant 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 |
| Group D ( (L-Ornithine L- Aspartate) LOLA + Lactulose) | Experimental | Drug: L-ornithine-L-aspartate plus latuloseGroup 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) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Probiotic plus lactuloseAlso: Ecotec plus DuphalacProbiotic and lactulose will be administered per the dose and schedule specified in the arms. | Drug | Group C (Probiotic + lactulose) |
| Rifaximin plus lactuloseAlso: Rifaxa plus DuphalacRifaximin and lactulose will be administered per the dose and schedule specified in the arms. | Drug | Group B (Rifaximin + lactulose) |
| L-ornithine-L-aspartate plus latuloseAlso: Levijon concentrate for infusion plus DuphalacLOLA and lactulose will be administered per the dose and schedule specified in the arms. | Drug | Group D ( (L-Ornithine L- Aspartate) LOLA + Lactulose) |
| LactuloseAlso: DuphalacLactulose will be administered per the dose and schedule specified in the arms. | Drug | Group A (Lactulose) |
Primary outcome
Number of participants of overt hepatic encephalopathy are treated by observing reversal in grades by using West Haven Criteria.
Time frame: From the time of enrollment till the end of treatment (day 5) in the trial.
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.
3 secondary outcomes
Time of recovery from encephalopathy (Days)
Time frame: Time of participation in the study assessed up to 5 days.
Liver disease severity
Time frame: time of participation in the trial till the end of treatment (day 5)
length of hospital days
Time frame: time of participation in the study till the patient is discharged or died or till 28 days whichever occur earlier.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2025.
- Derived from this study: PubMed 41272855Shahbaz 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.
- Individual participant dataSharing planned: No
Related trials for Overt Hepatic Encephalopathy
Not yet recruiting
Effect of Mini-Program Monitoring on Hepatic Encephalopathy in Post-TIPS Patients
Hepatic Encephalopathy, Liver Cirrhosis
Not yet recruiting
Personalized Nutritional Intervention in Patients Undergoing TIPS Insertion for Refractory Ascites to Prevent Overt Hepatic Encephalopathy
Cirrhosis, Refractory Ascites
Recruiting
Pilot Open-Label Trial of Resistant Potato Starch in Patients With Cirrhosis and Overt Hepatic Encephalopathy
Hepatic Encephalopathy, Cirrhosis
Not yet recruiting
UDCA to Prevent Post-TIPS Hepatic Encephalopathy
Hepatic Encephalopathy (HE), TIPS
Recruiting
Human Albumin Infusion in Liver Cirrhosis and Overt Hepatic Encephalopathy (HACHE)
Overt Hepatic Encephalopathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
QurratulAin Jamil, PhD principal investigator
The Islami University of Bahawalpur
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Probiotic plus lactulose, Rifaximin plus lactulose and L-ornithine-L-aspartate plus latulose in people with Overt Hepatic Encephalopathy, run by Qurratul Ain Jamil at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants of overt hepatic encephalopathy are treated by observing reversal in grades by using West Haven Criteria. (time frame: From the time of enrollment till the end of treatment (day 5) in the trial.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07037394, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2025.