Hepatic Encephalopathy Stage 2Phase 4NCT05920213
Efficacy of L-Ornithine L-Aspartate and Polyethylene Glycol in Cirrhotic Patients With Overt Hepatic Encephalopathy
A Phase 4 study testing Polyethylene Glycols, Lactulose oral solution and L-ornithine L-aspartate in people with Hepatic Encephalopathy Stage 2 and Hepatic Encephalopathy Stage 3, run by Jinnah Postgraduate Medical Centre at 6 sites in Pakistan.
Trial summary
The goal of this clinical trial is to compare the efficacy of L-ornithine L-aspartate and Polyethylene Glycol in Cirrhotic Patients with Overt Hepatic Encephalopathy. Participants will be asked to fill out a few questions on proforma that will obtain demographic information as well as information relating to the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatic Encephalopathy Stage 2, Hepatic Encephalopathy Stage 3, Hepatic Encephalopathy Stage 4
- What is being tested?
- Polyethylene Glycols, Lactulose oral solution and L-ornithine L-aspartate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 360 participants
- Where
- 6 sitesPakistan
- Study dates
- Oct 2023to Apr 2024
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Admitted cirrhotic patients above 18 years of age,
- diagnosed on clinical/ultrasound findings with HE (grade 2 or above) with or without precipitating factors.
Who cannot join
- Patients with hepatocellular carcinoma
- severe septicemia,
- active upper gastrointestinal bleeding and in a state of shock
- presence of underlying chronic renal failure (serum creatinine >1.5 mg/dl)
- presence of hepatorenal syndrome
- neurodegenerative disease
Show all 12Show fewer
- patients with a head injury and drug intoxication
- acute superimposed liver injury
- advanced cardiac or pulmonary derangements
- end-stage renal disease
- pregnant or breastfeeding mothers
- patients who are on sedatives, antidepressants, or benzodiazepines
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Pakistan6 sites
Medical ICU, Jinnah Postgraduate Medical Centre
Karachi, Sindh, 71550
CMC hospital
Larkana, Sindh
Ali Haider Mugheri, FCPS, +923334368045, dralihyder75@yahoo.com
Nishtar Medical Univeristy and Hospital
Multan, Punjab Province
Yasir Zaidi, FCPS, +923216332060, yasir.xaidi@gmail.com
Bolan Medical Complex Hospital
Quetta, Balochistan
Farhana Kayani, FCPS, +923323113852, farhana_kayani@hotmail.com
Sheikh Khalifa bin Zayed
Quetta, Balochistan
Farhana Kayani, FCPS, +92-3323113852, farhana_kayani@hotmail.com
Sheikh Zayed Medical College/Hospital
Rahim Yar Khan, Punjab Province
Muhammad Israr-ul-Haq, FCPS, +923332302984, drisrar83@gmail.com
About this study
Official title: HELP Trial: Efficacy of L-Ornithine L-Aspartate and Polyethylene Glycol in Cirrhotic Patients With Overt Hepatic Encephalopathy
The goal of this clinical trial is to compare the efficacy of L-ornithine L-aspartate and Polyethylene Glycol in Cirrhotic Patients with Overt Hepatic Encephalopathy.
Participants will be asked to fill out a few questions on proforma that will obtain demographic information as well as information relating to the patient's health. Treatments that they will receive after inclusion in the study, will be the standard treatment (Lactulose) along with additional medication as part of our research (LOLA or Polyethylene glycol).
Read the detailed description
This is a randomized control trial with the following objectives
- what is the efficacy of add-on LOLA therapy in patients of overt HE (Grade II and above) against the standard-of-care arm
- what is the efficacy of adding on polyethylene glycol (PEG) in overt HE (Grade II and above) against the standard-of-care arm
Randomization will be done using card randomization. three different color-coded cards will be kept. Any card will be randomly picked for the patient fulfilling inclusion criteria and will be treated according to the allocated treatment arm mentioned on the card
Patients will be diagnosed on the basis of Modified West Haven Criteria. For diagnosis and prognosis, the following tools will be used:
- Modified West Haven criteria and Glasgow coma scale will be used to assess the mental state.
- CLIF-C ADs and CLIF SOFA score will be used as a prognostic score for predicting mortality in hospitalized patients.
- Overt HE patients will be graded using the Hepatic encephalopathy grading instrument (HEGI).
- Child-Pugh classification and MELD scoring will be used to assess the severity of chronic liver disease and cirrhosis.
Written informed consent will be obtained from the immediate attendant of the patient. All ethical considerations will be followed.
Our research has been approved by Jinnah Sindh Medical University, Karachi. For this approval, the investigators have made every effort to ensure the confidentiality of research data collected from all our participants in this survey. The information collected will be stored with the investigators only in the form of de-identified information and will be retained in a secure place under lock and key. Any results that will be generated will be presented on a collective basis, and will not contain the participant's name or any other personal details.
Data entry and analysis will be done using SPSS Software version 23. Study analysis will be done using the principle of intention to treat. Primary and secondary outcomes will be studied among intervention and standard-of-care groups at a Confidence Interval of 95%. The chi-square test will be used to find the association of independent variables like age, gender, and HE grades with interventional therapies. Independent t-test will be used to compare mean scores between groups.
- Conditions
- Hepatic Encephalopathy Stage 2, Hepatic Encephalopathy Stage 3, Hepatic Encephalopathy Stage 4
- Being tested
- Polyethylene Glycols, Lactulose oral solution, L-ornithine L-aspartate
- Keywords
- Lactulose / therapeutic use, Liver Cirrhosis / drug therapy, Ornithine, Aspartic Acid / therapeutic use, Liver Cirrhosis / complications, Hepatic Encephalopathy / drug therapy*, Polyethylene Glycols / therapeutic use*, Gastrointestinal Agents / therapeutic use*
- Medical subject headings
- Hepatic Encephalopathy, Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Polyethylene GlycolsDrug
280g/ 24 hours for 5 days
Lactulose oral solutionDrug
60-120 ml per day for 5 days
L-ornithine L-aspartateDrug
30g/24 hours in 3 divided doses for 5 days
| Study group | Role | What they receive |
|---|---|---|
| Lactulose AND LOLA | Experimental | Lactulose which is the standard of care treatment will be administered with the experimental drug L-ornithine L-aspartate (LOLA). Receives: Drug: Lactulose oral solution; Drug: L-ornithine L-aspartate |
| Lactulose and PEG | Experimental | Lactulose which is the standard of care treatment will be administered with the experimental drug polyethylene glycol (PEG). Receives: Drug: Polyethylene Glycols; Drug: Lactulose oral solution |
| Lactulose | Active comparator | This group will receive Lactulose only which is the standard of care treatment. Receives: Drug: Lactulose oral solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patient recovery among all groups through a change in mental state.
Change of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale. A decrease in the grade will be a better outcome.
Measured: Change will be assessed at enrollment.
Patient recovery among all groups through a change in mental state.
A change of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale. A decrease in the grade will be a better outcome.
Measured: Change will be assessed at 24 hours post enrollment.
Patient recovery among all groups through a change in mental state.
A change of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale. A decrease in the grade will be a better outcome.
Measured: A change will be assessed at 48 hours post enrollment.
Patient recovery among all groups through a change in mental state.
A change of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale. A decrease in the grade will be a better outcome.
Measured: A change will be assessed at 72 hours post enrollment.
Patient recovery among all groups through a change in mental state.
A change of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale. A decrease in the grade will be a better outcome.
Measured: A change will be assessed at 96 hours post enrollment.
Patient recovery among all groups through a change in mental state.
A change of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale. A decrease in the grade will be a better outcome.
Measured: A change will be assessed at 120 hours post enrollment.
Patient recovery among all groups through a change in mental state.
A change of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale. A decrease in the grade will be a better outcome.
Measured: A change will be assessed at 144 hours post enrollment.
Secondary outcomes (5)
A change in Quality of Life will be assessed through SF-36
A change in the quality of life will be assessed using a validated Urdu translation of the Rand Short Form 36 item survey (SF-36 U). The lower the score the more disability. The higher the score the less disability
Measured: Quality of life will be assessed at 28th day post enrollment.
A change in Quality of Life will be assessed through SF-36
A change in the quality of life will be assessed using a validated Urdu translation of the Rand Short Form 36 item survey (SF-36 U).The lower the score the more disability. The higher the score the less disability
Measured: Quality of life will be assessed at 84th day post enrollment.
A change in mortality rate
It will be observed through weekly calls and monthly visits.
Measured: it will be inquired at 7th day post enrollment.
A change in mortality rate
It will be observed through weekly calls and monthly visits.
Measured: it will be inquired at 28th day post enrollment.
A change in mortality rate
It will be observed through weekly calls and monthly visits.
Measured: it will be inquired at 84th day post enrollment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2023
- Study startOct 2023 (estimated)
- Primary completionApr 2024 (estimated)
- Study completionApr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic Encephalopathy Stage 2Studies 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
- Factorial
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 360 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jinnah Postgraduate Medical Centre
- Sponsor type
- Other government
- Responsible party
- Principal investigator, ZA, Jinnah Postgraduate Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05920213
- Sponsor's protocol ID
- JSMU/IRB/2022/673
- Status last verified
- Jul 2023
- First submitted
- 16 Jun 2023
- Last updated
- 13 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HELP Trial: Efficacy of L-Ornithine L-Aspartate and Polyethylene Glycol in Cirrhotic Patients With Overt Hepatic Encephalopathy
- ClinicalTrials.gov ID
- NCT05920213
- Acronym / sponsor ID
- JSMU/IRB/2022/673
- Conditions
- Hepatic Encephalopathy Stage 2, Hepatic Encephalopathy Stage 3, Hepatic Encephalopathy Stage 4
- Keywords
- Lactulose / therapeutic use, Liver Cirrhosis / drug therapy, Ornithine, Aspartic Acid / therapeutic use, Liver Cirrhosis / complications, Hepatic Encephalopathy / drug therapy*, Polyethylene Glycols / therapeutic use*, Gastrointestinal Agents / therapeutic use*
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 360 participants (estimated)
- Lead sponsor
- Jinnah Postgraduate Medical CentreOther government
- Study start
- Oct 2023 (estimated)
- Primary completion
- Apr 2024 (estimated)
- Study completion
- Apr 2024 (estimated)
- First posted
- 27 Jun 2023 (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 clinical trial is to compare the efficacy of L-ornithine L-aspartate and Polyethylene Glycol in Cirrhotic Patients with Overt Hepatic Encephalopathy.
Participants will be asked to fill out a few questions on proforma that will obtain demographic information as well as information relating to the patient's health. Treatments that they will receive after inclusion in the study, will be the standard treatment (Lactulose) along with additional medication as part of our research (LOLA or Polyethylene glycol).
Detailed description
This is a randomized control trial with the following objectives
- what is the efficacy of add-on LOLA therapy in patients of overt HE (Grade II and above) against the standard-of-care arm
- what is the efficacy of adding on polyethylene glycol (PEG) in overt HE (Grade II and above) against the standard-of-care arm
Randomization will be done using card randomization. three different color-coded cards will be kept. Any card will be randomly picked for the patient fulfilling inclusion criteria and will be treated according to the allocated treatment arm mentioned on the card
Patients will be diagnosed on the basis of Modified West Haven Criteria. For diagnosis and prognosis, the following tools will be used:
- Modified West Haven criteria and Glasgow coma scale will be used to assess the mental state.
- CLIF-C ADs and CLIF SOFA score will be used as a prognostic score for predicting mortality in hospitalized patients.
- Overt HE patients will be graded using the Hepatic encephalopathy grading instrument (HEGI).
- Child-Pugh classification and MELD scoring will be used to assess the severity of chronic liver disease and cirrhosis.
Written informed consent will be obtained from the immediate attendant of the patient. All ethical considerations will be followed.
Our research has been approved by Jinnah Sindh Medical University, Karachi. For this approval, the investigators have made every effort to ensure the confidentiality of research data collected from all our participants in this survey. The information collected will be stored with the investigators only in the form of de-identified information and will be retained in a secure place under lock and key. Any results that will be generated will be presented on a collective basis, and will not contain the participant's name or any other personal details.
Data entry and analysis will be done using SPSS Software version 23. Study analysis will be done using the principle of intention to treat. Primary and secondary outcomes will be studied among intervention and standard-of-care groups at a Confidence Interval of 95%. The chi-square test will be used to find the association of independent variables like age, gender, and HE grades with interventional therapies. Independent t-test will be used to compare mean scores between groups.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Lactulose AND LOLA | Experimental | Drug: Lactulose oral solution, Drug: L-ornithine L-aspartateLactulose which is the standard of care treatment will be administered with the experimental drug L-ornithine L-aspartate (LOLA). |
| Lactulose and PEG | Experimental | Drug: Polyethylene Glycols, Drug: Lactulose oral solutionLactulose which is the standard of care treatment will be administered with the experimental drug polyethylene glycol (PEG). |
| Lactulose | Active comparator | Drug: Lactulose oral solutionThis group will receive Lactulose only which is the standard of care treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Admitted cirrhotic patients above 18 years of age,
- diagnosed on clinical/ultrasound findings with HE (grade 2 or above) with or without precipitating factors.
Key exclusion criteria (12 listed)
- Patients with hepatocellular carcinoma
- severe septicemia,
- active upper gastrointestinal bleeding and in a state of shock
- presence of underlying chronic renal failure (serum creatinine >1.5 mg/dl)
- presence of hepatorenal syndrome
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 |
|---|---|---|
| Polyethylene Glycols280g/ 24 hours for 5 days | Drug | Lactulose and PEG |
| Lactulose oral solution60-120 ml per day for 5 days | Drug | Lactulose, Lactulose AND LOLA, Lactulose and PEG |
| L-ornithine L-aspartate30g/24 hours in 3 divided doses for 5 days | Drug | Lactulose AND LOLA |
Primary outcome
Patient recovery among all groups through a change in mental state.
Time frame: Change will be assessed at enrollment.
Change of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale. A decrease in the grade will be a better outcome.
Patient recovery among all groups through a change in mental state.
Time frame: Change will be assessed at 24 hours post enrollment.
A change of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale. A decrease in the grade will be a better outcome.
Patient recovery among all groups through a change in mental state.
Time frame: A change will be assessed at 48 hours post enrollment.
A change of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale. A decrease in the grade will be a better outcome.
Patient recovery among all groups through a change in mental state.
Time frame: A change will be assessed at 72 hours post enrollment.
A change of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale. A decrease in the grade will be a better outcome.
Patient recovery among all groups through a change in mental state.
Time frame: A change will be assessed at 96 hours post enrollment.
A change of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale. A decrease in the grade will be a better outcome.
Patient recovery among all groups through a change in mental state.
Time frame: A change will be assessed at 120 hours post enrollment.
A change of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale. A decrease in the grade will be a better outcome.
Patient recovery among all groups through a change in mental state.
Time frame: A change will be assessed at 144 hours post enrollment.
A change of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale. A decrease in the grade will be a better outcome.
5 secondary outcomes
A change in Quality of Life will be assessed through SF-36
Time frame: Quality of life will be assessed at 28th day post enrollment.
A change in Quality of Life will be assessed through SF-36
Time frame: Quality of life will be assessed at 84th day post enrollment.
A change in mortality rate
Time frame: it will be inquired at 7th day post enrollment.
A change in mortality rate
Time frame: it will be inquired at 28th day post enrollment.
A change in mortality rate
Time frame: it will be inquired at 84th day post enrollment.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2023.
- Individual participant dataSharing planned: No
Related trials for Hepatic Encephalopathy Stage 2
Active, not recruitingPhase 1/2
RTX001 Autologous Engineered Macrophages for Liver Cirrhosis
End-stage Liver Disease (ESLD), Cirrhosis, Liver
Active, not recruitingObservational study
Study in Patients With Decompensated Liver Cirrhosis
Liver Cirrhosis
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.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Polyethylene Glycols, Lactulose oral solution and L-ornithine L-aspartate in people with Hepatic Encephalopathy Stage 2 and Hepatic Encephalopathy Stage 3, run by Jinnah Postgraduate Medical Centre at 6 sites 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 2 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 13 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zeeshan Ali, FCPS (+923211000393, dr.zeeshan.j@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient recovery among all groups through a change in mental state. (time frame: Change will be assessed at enrollment.). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Jul 2023; AzTrials last refreshed its copy on 8 Nov 2026.