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

NCT05920213 | Unknown Phase 4 DMC

• 1 other identifier: JSMU/IRB/2022/673
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 6

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).

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*

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (5)

• A change in Quality of Life will be assessed through SF-36

  Quality of life will be assessed at 28th day post enrollment.

• A change in Quality of Life will be assessed through SF-36

  Quality of life will be assessed at 84th day post enrollment.

• A change in mortality rate

  it will be inquired at 7th day post enrollment.

• A change in mortality rate

  it will be inquired at 28th day post enrollment.

• A change in mortality rate

  it will be inquired at 84th day post enrollment.

Study Arms (3)

Lactulose AND LOLA

EXPERIMENTAL

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

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).

Drug: Polyethylene Glycols; Drug: Lactulose oral solution

Lactulose

ACTIVE COMPARATOR

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

Drug: Lactulose oral solution

Interventions

Polyethylene Glycols DRUG

280g/ 24 hours for 5 days

Lactulose and PEG

Lactulose oral solution DRUG

60-120 ml per day for 5 days

Lactulose; Lactulose AND LOLA; Lactulose and PEG

L-ornithine L-aspartate DRUG

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

Lactulose AND LOLA

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jinnah Postgraduate Medical Centre: lead

Study Sites (6)

Bolan Medical Complex Hospital

Quetta, Balochistan, Pakistan

Location

Sheikh Khalifa bin Zayed

Quetta, Balochistan, Pakistan

Location

Nishtar Medical Univeristy and Hospital

Multan, Punjab Province, Pakistan

Location

Sheikh Zayed Medical College/Hospital

Rahim Yar Khan, Punjab Province, Pakistan

Location

Medical ICU, Jinnah Postgraduate Medical Centre

Karachi, Sindh, 71550, Pakistan

Location

CMC hospital

Larkana, Sindh, Pakistan

Location

MeSH Terms

Conditions

Hepatic Encephalopathy; Liver Cirrhosis

Interventions

Polyethylene Glycols; Lactulose; ornithylaspartate

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethylene Glycols; Glycols; Alcohols; Organic Chemicals; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Central Study Contacts

Zeeshan Ali, FCPS

CONTACT

+923211000393; dr.zeeshan.j@gmail.com

Shamim Kausar, FCPS

CONTACT

+923343093627; drshamimahsan@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: June 16, 2023
• First Posted: June 27, 2023
• Study Start: October 1, 2023
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: July 13, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

PA (6)