Clinical trial NCT04436601: Polyethylene Glycol Versus Lactulose on Hepatic Encephalopathy in Patients With Cirrhosis;(PEGHE Trial)
Official title: Effect of Polyethylene Glycol Versus Lactulose on Hepatic Encephalopathy in Patients With Liver Cirrhosis; a Randomized Clinical Trial (PEGHE Trial)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hepatic Encephalopathy
Lead sponsor: Aga Khan University
Sponsor class: OTHER
First posted: 2020-06-18
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Resolution of Hepatic Encephalopathy
timeFrame: Change in HESA score at 24 hours, 48 hours and if applicable, 72 hours of drug administration
Secondary outcomes:
measure: Mean Length of inpatient stay in hours
timeFrame: at time of patient discharge, an average of 72 hours
measure: 3 months outcome (readmission with Hepatic Encephalopathy)
timeFrame: 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
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Aga Khan University
state: Sindh
Study officials:
affiliation: Aga Khan University
name: Om Parkash
role: PRINCIPAL_INVESTIGATOR
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