Clinical trial NCT05920213: Efficacy of L-Ornithine L-Aspartate and Polyethylene Glycol in Cirrhotic Patients With Overt Hepatic Encephalopathy
Official title: HELP Trial: Efficacy of L-Ornithine L-Aspartate and Polyethylene Glycol in Cirrhotic Patients With Overt Hepatic Encephalopathy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
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*
Lead sponsor: Jinnah Postgraduate Medical Centre
Sponsor class: OTHER_GOV
First posted: 2023-06-27
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Patient recovery among all groups through a change in mental state.
timeFrame: Change will be assessed at enrollment.
measure: Patient recovery among all groups through a change in mental state.
timeFrame: Change will be assessed at 24 hours post enrollment.
measure: Patient recovery among all groups through a change in mental state.
timeFrame: A change will be assessed at 48 hours post enrollment.
measure: Patient recovery among all groups through a change in mental state.
timeFrame: A change will be assessed at 72 hours post enrollment.
measure: Patient recovery among all groups through a change in mental state.
timeFrame: A change will be assessed at 96 hours post enrollment.
measure: Patient recovery among all groups through a change in mental state.
timeFrame: A change will be assessed at 120 hours post enrollment.
measure: Patient recovery among all groups through a change in mental state.
timeFrame: A change will be assessed at 144 hours post enrollment.
Secondary outcomes:
measure: A change in Quality of Life will be assessed through SF-36
timeFrame: Quality of life will be assessed at 28th day post enrollment.
measure: A change in Quality of Life will be assessed through SF-36
timeFrame: Quality of life will be assessed at 84th day post enrollment.
measure: A change in mortality rate
timeFrame: it will be inquired at 7th day post enrollment.
measure: A change in mortality rate
timeFrame: it will be inquired at 28th day post enrollment.
measure: A change in mortality rate
timeFrame: it will be inquired at 84th day post enrollment.
Other outcomes:
Locations:
city: Quetta
country: Pakistan
facility: Bolan Medical Complex Hospital
state: Balochistan
city: Quetta
country: Pakistan
facility: Sheikh Khalifa bin Zayed
state: Balochistan
city: Multan
country: Pakistan
facility: Nishtar Medical Univeristy and Hospital
state: Punjab
city: Rahim Yar Khan
country: Pakistan
facility: Sheikh Zayed Medical College/Hospital
state: Punjab
city: Karachi
country: Pakistan
facility: Medical ICU, Jinnah Postgraduate Medical Centre
state: Sindh
city: Larkana
country: Pakistan
facility: CMC hospital
state: Sindh
Study officials:
References: