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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatic Encephalopathy Stage 2; Hepatic Encephalopathy Stage 3; Hepatic Encephalopathy Stage 4
• Intervention / Treatment: Drug: Lactulose oral solution; Drug: L-ornithine L-aspartate; Drug: Polyethylene Glycols

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 Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Zeeshan Ali, FCPS; Phone Number: +923211000393; Email: dr.zeeshan.j@gmail.com
• Study Contact Backup: Name: Shamim Kausar, FCPS; Phone Number: +923343093627; Email: drshamimahsan@gmail.com

Study Locations

• Pakistan
  • Balochistan
    • Quetta, Balochistan, Pakistan
      • Bolan Medical Complex Hospital
      • Contact: Farhana Kayani, FCPS; Phone Number: +923323113852; Email: farhana_kayani@hotmail.com
    • Quetta, Balochistan, Pakistan
      • Sheikh Khalifa bin Zayed
      • Contact: Farhana Kayani, FCPS; Phone Number: +92-3323113852; Email: farhana_kayani@hotmail.com
  • Punjab
    • Multan, Punjab, Pakistan
      • Nishtar Medical Univeristy and Hospital
      • Contact: Yasir Zaidi, FCPS; Phone Number: +923216332060; Email: yasir.xaidi@gmail.com
    • Rahim Yar Khan, Punjab, Pakistan
      • Sheikh Zayed Medical college/hospital
      • Contact: Muhammad Israr-ul-Haq, FCPS; Phone Number: +923332302984; Email: drisrar83@gmail.com
  • Sindh
    • Karachi, Sindh, Pakistan, 71550
      • Medical ICU, Jinnah Postgraduate Medical Centre
    • Larkana, Sindh, Pakistan
      • CMC hospital
      • Contact: Ali Haider Mugheri, FCPS; Phone Number: +923334368045; Email: dralihyder75@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lactulose AND LOLA; Lactulose which is the standard of care treatment will be administered with the experimental drug L-ornithine L-aspartate (LOLA).	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: Lactulose and PEG; Lactulose which is the standard of care treatment will be administered with the experimental drug polyethylene glycol (PEG).	Drug: Lactulose oral solution; 60-120 ml per day for 5 days; Drug: Polyethylene Glycols; 280g/ 24 hours for 5 days
Active Comparator: Lactulose; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	A change will be assessed at 144 hours post enrollment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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.	it will be inquired at 7th day post enrollment.
A change in mortality rate	It will be observed through weekly calls and monthly visits.	it will be inquired at 28th day post enrollment.
A change in mortality rate	It will be observed through weekly calls and monthly visits.	it will be inquired at 84th day post enrollment.

Collaborators and Investigators

• Sponsor: Jinnah Postgraduate Medical Centre

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: June 16, 2023
• First Submitted That Met QC Criteria: June 16, 2023
• First Posted (Actual): June 27, 2023

Study Record Updates

• Last Update Posted (Actual): July 13, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Ornithine; Lactulose / therapeutic use; Liver Cirrhosis / drug therapy; Aspartic Acid / therapeutic use; Liver Cirrhosis / complications; Hepatic Encephalopathy / drug therapy*; Polyethylene Glycols / therapeutic use*; Gastrointestinal Agents / therapeutic use*
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hepatic Encephalopathy; Brain Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Agents; Gastrointestinal Agents; Excitatory Amino Acid Agonists; Lactulose; N-Methylaspartate
• Other Study ID Numbers: JSMU/IRB/2022/673

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No