Efficacy of L-Ornithine L-Aspartate and Polyethylene Glycol in Cirrhotic Patients With Overt Hepatic Encephalopathy

Sponsor

Jinnah Postgraduate Medical Centre (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05920213

Collaborator

(none)

360

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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 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).

Condition or Disease	Intervention/Treatment	Phase
Hepatic Encephalopathy Stage 2 Hepatic Encephalopathy Stage 3 Hepatic Encephalopathy Stage 4	Drug: Polyethylene Glycols Drug: Lactulose oral solution Drug: L-ornithine L-aspartate	Phase 4

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 the Jinnah Sindh Medical University, Karachi. For this approval, we 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 your 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

Study Type:

Interventional

Anticipated Enrollment :

360 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Single (Participant)

Masking Description:

participants' attendants will also be masked and will give consent for the study in case the participant is admitted to the Intensive care unit and is not mentally stable to give consent.

Primary Purpose:

Treatment

Official Title:

HELP Trial: Efficacy of L-Ornithine L-Aspartate and Polyethylene Glycol in Cirrhotic Patients With Overt Hepatic Encephalopathy

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Apr 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A Lactulose which is the standard of care treatment will be administered with the experimental drug L-ornithine L-aspartate.	Drug: Lactulose oral solution 60-120 ml per day for 5 days Drug: L-ornithine L-aspartate 30g/24 hours in 3 divided doses for 5 days
Experimental: Group B Lactulose which is the standard of care treatment will be administered with the experimental drug polyethylene glycol.	Drug: Polyethylene Glycols 280g/ 24 hours for 5 days Drug: Lactulose oral solution 60-120 ml per day for 5 days
Active Comparator: Group C This group will receive Lactulose only which is the standard of care treatment.	Drug: Lactulose oral solution 60-120 ml per day for 5 days

Arm

Intervention/Treatment

Experimental: Group A

Lactulose which is the standard of care treatment will be administered with the experimental drug L-ornithine L-aspartate.

Drug: Lactulose oral solution

60-120 ml per day for 5 days

Drug: L-ornithine L-aspartate

30g/24 hours in 3 divided doses for 5 days

Experimental: Group B

Lactulose which is the standard of care treatment will be administered with the experimental drug polyethylene glycol.

Drug: Polyethylene Glycols

280g/ 24 hours for 5 days

Drug: Lactulose oral solution

60-120 ml per day for 5 days

Active Comparator: Group C

This group will receive Lactulose only which is the standard of care treatment.

Drug: Lactulose oral solution

60-120 ml per day for 5 days

Outcome Measures

Primary Outcome Measures

Patient recovery among all groups through improvement in mental state. [Improvement will be assessed at enrollment.]
Improvement of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale.
Patient recovery among all groups through improvement in mental state. [Improvement will be assessed at 24 hours post enrollment.]
Improvement of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale.
Patient recovery among all groups through improvement in mental state. [Improvement will be assessed at 48 hours post enrollment.]
Improvement of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale.
Patient recovery among all groups through improvement in mental state. [Improvement will be assessed at 72 hours post enrollment.]
Improvement of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale.
Patient recovery among all groups through improvement in mental state. [Improvement will be assessed at 96 hours post enrollment.]
Improvement of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale.
Patient recovery among all groups through improvement in mental state. [Improvement will be assessed at 120 hours post enrollment.]
Improvement of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale.
Patient recovery among all groups through improvement in mental state. [Improvement will be assessed at 144 hours post enrollment.]
Improvement of at least one grade in the mental state based on the modified West Haven criteria and hepatic encephalopathy grading scale.

Secondary Outcome Measures

Improvement in Quality of Life [Quality of life will be assessed at 28th day post enrollment.]
Improvement in quality of life will be assessed using validated Urdu translation of Rand Short Form 36 item survey (SF-36 U)
Improvement in Quality of Life [Quality of life will be assessed at 84th day post enrollment.]
Improvement in quality of life will be assessed using validated Urdu translation of Rand Short Form 36 item survey (SF-36 U)
Improvement in mortality rate [it will be inquired at 7th day post enrollment.]
It will be observed through weekly calls and monthly visits.
Improvement in mortality rate [it will be inquired at 28th day post enrollment.]
It will be observed through weekly calls and monthly visits.
Improvement in mortality rate [it will be inquired at 84th day post enrollment.]
It will be observed through weekly calls and monthly visits.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Admitted cirrhotic patients above 18 years of age,
diagnosed on clinical/ultrasound findings with HE (grade 2 or above) with or without precipitating factors.

Exclusion Criteria:

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
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bolan Medical Complex Hospital	Quetta	Balochistan	Pakistan
2	Sheikh Khalifa bin Zayed	Quetta	Balochistan	Pakistan
3	Nishtar Medical Univeristy and Hospital	Multan	Punjab	Pakistan
4	Sheikh Zayed Medical College/Hospital	Rahim Yar Khan	Punjab	Pakistan
5	Medical ICU, Jinnah Postgraduate Medical Centre	Karachi	Sindh	Pakistan	71550
6	CMC hospital	Larkana	Sindh	Pakistan