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

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ClinicalTrials.gov Identifier: NCT04436601
Recruitment Status : Recruiting
First Posted : June 18, 2020
Last Update Posted : June 18, 2020
Sponsor:
Information provided by (Responsible Party):
Om Parkash, Aga Khan University

Tracking Information
First Submitted Date  ICMJE May 23, 2020
First Posted Date  ICMJE June 18, 2020
Last Update Posted Date June 18, 2020
Actual Study Start Date  ICMJE March 9, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2020)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2020)
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Polyethylene Glycol Versus Lactulose on Hepatic Encephalopathy in Patients With Cirrhosis;(PEGHE Trial)
Official Title  ICMJE Effect of Polyethylene Glycol Versus Lactulose on Hepatic Encephalopathy in Patients With Liver Cirrhosis; a Randomized Clinical Trial (PEGHE Trial)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
It would be a double blinded study. Investigator assessing the participants and following the patient will be masked to the allocation of treatment group. Participants would be masked to their treatment group as well.
Primary Purpose: Treatment
Condition  ICMJE Hepatic Encephalopathy
Intervention  ICMJE
  • 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.
  • Drug: Lactulose
    Lactulose (standard of care) will be administered to half of the study patients and their response recorded.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Lactulose
  • 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
    Intervention: Drug: Polyethylene Glycols
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 17, 2020)
102
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 1, 2021
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Om Parkash +923333509749 om.parkash@aku.edu
Contact: Asra tus Saleha Siddiqui +923323262516 asra.siddiqui@aku.edu
Listed Location Countries  ICMJE Pakistan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04436601
Other Study ID Numbers  ICMJE 191002MED
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Combined data, relevant to the study publication will be made available
Responsible Party Om Parkash, Aga Khan University
Study Sponsor  ICMJE Aga Khan University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Om Parkash Aga Khan University
PRS Account Aga Khan University
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP