Polyethylene Glycol Versus Lactulose on Hepatic Encephalopathy in Patients With Cirrhosis;(PEGHE Trial) (PEGHE)

April 18, 2023 updated by: Om Parkash, Aga Khan University

Effect of Polyethylene Glycol Versus Lactulose on Hepatic Encephalopathy in Patients With Liver Cirrhosis; a Randomized Clinical Trial (PEGHE Trial)

Hepatic Encephaopathy is a common complication occurring in patients with Liver cirrhosis. Patients usually develop mild confusion, sleep disturbance or obtundation. It occurs due to accumulation of excess ammonia in the brain, as the liver is unable to metabolize the ammonia. The common gold standard treatment recommended for patients with Hepatic Encephalopathy is Lactulose syrup. This is a non absorbable sugar, often combined with an antibiotic called Rifaxamine to treat this condition.

Polyethylene glycol is in a class of medications called osmotic laxatives which works by causing water to be retained with the stool. PEG and lactulose, when used together, result in faster resolution of symptoms suggesting that PEG may be superior to standard lactulose therapy in these patients.

Non-absorbable sugars like lactulose are associated with non-serious (mainly gastrointestinal) adverse events like diarrhea and bloating Hence, due to the side effect profile, newer drugs continue to be tested for treatment of Hepatic Encephalopathy.

The aim of this research project is to compare the effect of PEG versus lactulose for treatment of HE in patients with liver cirrhosis. The investigators want to compare the resolution of HE as the main outcome. In addition, they will compare length of stay, non-serious (mainly gastrointestinal) adverse events, and 3 months outcome. The investigators hypothesize that rapid purgation of the gut using PEG may resolve HE more effectively than lactulose.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Hepatic encephalopathy (HE) is a common neuropsychiatric complication of liver cirrhosis manifested by mild confusion, sleep disturbance or obtundation. Lactulose treatment has long been the standard of care, which presumably acidifies stool and eradicates toxic metabolites. However a third of these patients with hepatic encephalopathy do not respond to this standard treatment and have refractory HE. Hence newer drugs with effective improvement in HE and better side effect profile are still being tested.

Polyethylene glycol (PEG) is in a class of medications called osmotic laxatives which works by causing water to be retained with the stool. PEG and lactulose, when used together, result in rapid overt HE resolution within 24 hours compared to the standard-of-care lactulose, suggesting that PEG may be superior to standard lactulose therapy in patients with cirrhosis hospitalized for acute HE.

Rationale Non-absorbable disaccharides like lactulose are associated with non-serious (mainly gastrointestinal) adverse events like diarrhea and bloating, hence, due to the side effect profile, newer drugs continue to be tested for treatment of HE.

Hypothesis and Aim The aim of this research project is to compare the effect of PEG with Lactulose for treatment of Hepatic Encephalopathy in patients with liver cirrhosis. The investigators want to compare the resolution of HE as the main outcome. In addition, they would compare length of stay, non-serious (mainly gastrointestinal) adverse events, and 3 months outcome. The investigators hypothesize that rapid purgation of the gut using PEG may resolve HE more effectively than lactulose.

These aims are original in that the investigators aim to test this hypothesis on a different patient population (South Asian), where the predominant cause of cirrhosis is due to viral hepatitis C and B. In addition,the investigators will also look at the effect of PEG v lactulose on 3 months outcome in this study.

Significance The significance of this proposal is that if the investigators can prove the hypothesis, it will add to the currently limited evidence on use of PEG in treatment of HE in the world. PEG might have a better side effect profile when compared to lactulose. Based on current market pricing of lactulose, if PEG is found to have favorable outcome then it might be more cost effective as well. Hence PEG might be a useful alternative in 30% of those who don't respond to lactulose, if PEG shows favorable outcome.

Objective Primary: To determine the effect of PEG versus Lactulose on resolution of HE in patients with liver cirrhosis during inpatient stay at 24 hours, 48 hours and 72 hours .

Secondary: To determine the effect of Lactulose versus PEG on length of stay, and 3 months outcome in patients with liver cirrhosis.

Study Type

Interventional

Enrollment (Anticipated)

102

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Pakistan
    • Sindh
      • Karachi, Sindh, Pakistan, 75290
        • Recruiting
        • Aga Khan University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. All patients of 18-80 years admitted to Aga Khan University Hospital
  2. With Chronic liver disease: Chronic liver disease will be defined based on ultra-sonographic evidence of chronic liver disease including shrunken liver, dilated portal vein, splenomegaly.
  3. With Hepatic encephalopathy; Hepatic encephalopathy will be defined as the onset of disorientation or asterixis according to The International Society for Hepatic Encephalopathy and Nitrogen Metabolism consensus and will be assessed using HESA score
  4. Presence of first degree relative for consent (Next of kin)

Exclusion Criteria:

  1. Allergy to PEG
  2. Bowel obstruction or perforation diagnosed clinically or on Xray
  3. Major psychiatric illness; on benzodiazepines
  4. Treated with locally acting antibiotics (rifaximin) in the previous 7 days;
  5. Active gastrointestinal tract bleeding
  6. Acute Liver failure:defined as coagulopathy (international normalized ratio >1.5) with any degree of AMS in the absence of underlying chronic liver disease (CLD)
  7. Female patients if pregnant or lactating

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Lactulose
90 ml of Lactulose dissolved in 750 ml of water administered orally by mouth or nasogastric tube (three doses within 24 hrs) continued up to 72 hours or until patient discharge, whichever comes first.
Drug: Lactulose
Lactulose (standard of care) will be administered to half of the study patients and their response recorded.
Experimental: PEG: Polyethylene Glycol
Three or four sachet of Movicol(PEG) will be dissolved in 750 ml of water and will be given over 24 hrs as 3 doses orally by mouth or Nasogastric tube and will continue up to 72 hours or until patient discharge, whichever comes first
Drug: Polyethylene Glycols
Polyethylene glycol will be administered to half of the study patients, and their response recorded and compared with that of the Lactulose arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Resolution of Hepatic Encephalopathy
Time Frame: Change in HESA score at 24 hours, 48 hours and if applicable, 72 hours of drug administration
Calculated using Hepatic Encephalopathy scoring Algorithm (HESA). Resolution is defined as reduction of at least 1 grade of HESA score after 24 hours, 48 hours and if applicable 72 hours of therapy during hospital stay
Change in HESA score at 24 hours, 48 hours and if applicable, 72 hours of drug administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Length of inpatient stay in hours
Time Frame: at time of patient discharge, an average of 72 hours
Duration of hospital stay will be recorded in hours
at time of patient discharge, an average of 72 hours
3 months outcome (readmission with Hepatic Encephalopathy)
Time Frame: The three month outcome will be assessed at clinic follow-up at 3 month or by phone call if patient is lost to follow up
Patient will be asked at 3 month follow up if there was any other readmission anywhere with Hepatic Encephalopathy
The three month outcome will be assessed at clinic follow-up at 3 month or by phone call if patient is lost to follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aga Khan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 9, 2020

Primary Completion (Anticipated)

December 30, 2023

Study Completion (Anticipated)

December 30, 2023

Study Registration Dates

First Submitted

May 23, 2020

First Submitted That Met QC Criteria

June 17, 2020

First Posted (Actual)

June 18, 2020

Study Record Updates

Last Update Posted (Actual)

April 19, 2023

Last Update Submitted That Met QC Criteria

April 18, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 191002MED

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Combined data, relevant to the study publication will be made available

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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