<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04436601</url>
  </required_header>
  <id_info>
    <org_study_id>191002MED</org_study_id>
    <nct_id>NCT04436601</nct_id>
  </id_info>
  <brief_title>Polyethylene Glycol Versus Lactulose on Hepatic Encephalopathy in Patients With Cirrhosis;(PEGHE Trial)</brief_title>
  <acronym>PEGHE</acronym>
  <official_title>Effect of Polyethylene Glycol Versus Lactulose on Hepatic Encephalopathy in Patients With Liver Cirrhosis; a Randomized Clinical Trial (PEGHE Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aga Khan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Aga Khan University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hepatic Encephaopathy is a common complication occurring in patients with Liver cirrhosis.&#xD;
      Patients usually develop mild confusion, sleep disturbance or obtundation. It occurs due to&#xD;
      accumulation of excess ammonia in the brain, as the liver is unable to metabolize the&#xD;
      ammonia. The common gold standard treatment recommended for patients with Hepatic&#xD;
      Encephalopathy is Lactulose syrup. This is a non absorbable sugar, often combined with an&#xD;
      antibiotic called Rifaxamine to treat this condition.&#xD;
&#xD;
      Polyethylene glycol is in a class of medications called osmotic laxatives which works by&#xD;
      causing water to be retained with the stool. PEG and lactulose, when used together, result in&#xD;
      faster resolution of symptoms suggesting that PEG may be superior to standard lactulose&#xD;
      therapy in these patients.&#xD;
&#xD;
      Non-absorbable sugars like lactulose are associated with non-serious (mainly&#xD;
      gastrointestinal) adverse events like diarrhea and bloating Hence, due to the side effect&#xD;
      profile, newer drugs continue to be tested for treatment of Hepatic Encephalopathy.&#xD;
&#xD;
      The aim of this research project is to compare the effect of PEG versus lactulose for&#xD;
      treatment of HE in patients with liver cirrhosis. The investigators want to compare the&#xD;
      resolution of HE as the main outcome. In addition, they will compare length of stay,&#xD;
      non-serious (mainly gastrointestinal) adverse events, and 3 months outcome. The investigators&#xD;
      hypothesize that rapid purgation of the gut using PEG may resolve HE more effectively than&#xD;
      lactulose.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hepatic encephalopathy (HE) is a common neuropsychiatric complication of liver cirrhosis&#xD;
      manifested by mild confusion, sleep disturbance or obtundation. Lactulose treatment has long&#xD;
      been the standard of care, which presumably acidifies stool and eradicates toxic metabolites.&#xD;
      However a third of these patients with hepatic encephalopathy do not respond to this standard&#xD;
      treatment and have refractory HE. Hence newer drugs with effective improvement in HE and&#xD;
      better side effect profile are still being tested.&#xD;
&#xD;
      Polyethylene glycol (PEG) is in a class of medications called osmotic laxatives which works&#xD;
      by causing water to be retained with the stool. PEG and lactulose, when used together, result&#xD;
      in rapid overt HE resolution within 24 hours compared to the standard-of-care lactulose,&#xD;
      suggesting that PEG may be superior to standard lactulose therapy in patients with cirrhosis&#xD;
      hospitalized for acute HE.&#xD;
&#xD;
      Rationale Non-absorbable disaccharides like lactulose are associated with non-serious (mainly&#xD;
      gastrointestinal) adverse events like diarrhea and bloating, hence, due to the side effect&#xD;
      profile, newer drugs continue to be tested for treatment of HE.&#xD;
&#xD;
      Hypothesis and Aim The aim of this research project is to compare the effect of PEG with&#xD;
      Lactulose for treatment of Hepatic Encephalopathy in patients with liver cirrhosis. The&#xD;
      investigators want to compare the resolution of HE as the main outcome. In addition, they&#xD;
      would compare length of stay, non-serious (mainly gastrointestinal) adverse events, and 3&#xD;
      months outcome. The investigators hypothesize that rapid purgation of the gut using PEG may&#xD;
      resolve HE more effectively than lactulose.&#xD;
&#xD;
      These aims are original in that the investigators aim to test this hypothesis on a different&#xD;
      patient population (South Asian), where the predominant cause of cirrhosis is due to viral&#xD;
      hepatitis C and B. In addition,the investigators will also look at the effect of PEG v&#xD;
      lactulose on 3 months outcome in this study.&#xD;
&#xD;
      Significance The significance of this proposal is that if the investigators can prove the&#xD;
      hypothesis, it will add to the currently limited evidence on use of PEG in treatment of HE in&#xD;
      the world. PEG might have a better side effect profile when compared to lactulose. Based on&#xD;
      current market pricing of lactulose, if PEG is found to have favorable outcome then it might&#xD;
      be more cost effective as well. Hence PEG might be a useful alternative in 30% of those who&#xD;
      don't respond to lactulose, if PEG shows favorable outcome.&#xD;
&#xD;
      Objective Primary: To determine the effect of PEG versus Lactulose on resolution of HE in&#xD;
      patients with liver cirrhosis during inpatient stay at 24 hours, 48 hours and 72 hours .&#xD;
&#xD;
      Secondary: To determine the effect of Lactulose versus PEG on length of stay, and 3 months&#xD;
      outcome in patients with liver cirrhosis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 9, 2020</start_date>
  <completion_date type="Anticipated">December 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2023</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <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.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Resolution of Hepatic Encephalopathy</measure>
    <time_frame>Change in HESA score at 24 hours, 48 hours and if applicable, 72 hours of drug administration</time_frame>
    <description>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</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Length of inpatient stay in hours</measure>
    <time_frame>at time of patient discharge, an average of 72 hours</time_frame>
    <description>Duration of hospital stay will be recorded in hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>3 months outcome (readmission with Hepatic Encephalopathy)</measure>
    <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</time_frame>
    <description>Patient will be asked at 3 month follow up if there was any other readmission anywhere with Hepatic Encephalopathy</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">102</enrollment>
  <condition>Hepatic Encephalopathy</condition>
  <arm_group>
    <arm_group_label>Lactulose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PEG: Polyethylene Glycol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Polyethylene Glycols</intervention_name>
    <description>Polyethylene glycol will be administered to half of the study patients, and their response recorded and compared with that of the Lactulose arm.</description>
    <arm_group_label>PEG: Polyethylene Glycol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lactulose</intervention_name>
    <description>Lactulose (standard of care) will be administered to half of the study patients and their response recorded.</description>
    <arm_group_label>Lactulose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. All patients of 18-80 years admitted to Aga Khan University Hospital&#xD;
&#xD;
          2. With Chronic liver disease: Chronic liver disease will be defined based on&#xD;
             ultra-sonographic evidence of chronic liver disease including shrunken liver, dilated&#xD;
             portal vein, splenomegaly.&#xD;
&#xD;
          3. With Hepatic encephalopathy; Hepatic encephalopathy will be defined as the onset of&#xD;
             disorientation or asterixis according to The International Society for Hepatic&#xD;
             Encephalopathy and Nitrogen Metabolism consensus and will be assessed using HESA score&#xD;
&#xD;
          4. Presence of first degree relative for consent (Next of kin)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Allergy to PEG&#xD;
&#xD;
          2. Bowel obstruction or perforation diagnosed clinically or on Xray&#xD;
&#xD;
          3. Major psychiatric illness; on benzodiazepines&#xD;
&#xD;
          4. Treated with locally acting antibiotics (rifaximin) in the previous 7 days;&#xD;
&#xD;
          5. Active gastrointestinal tract bleeding&#xD;
&#xD;
          6. Acute Liver failure:defined as coagulopathy (international normalized ratio &gt;1.5) with&#xD;
             any degree of AMS in the absence of underlying chronic liver disease (CLD)&#xD;
&#xD;
          7. Female patients if pregnant or lactating&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Om Parkash</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aga Khan University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Om Parkash</last_name>
    <phone>+923333509749</phone>
    <email>om.parkash@aku.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Asra tus Saleha Siddiqui</last_name>
    <phone>+923323262516</phone>
    <email>asra.siddiqui@aku.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Aga Khan University</name>
      <address>
        <city>Karachi</city>
        <state>Sindh</state>
        <zip>75290</zip>
        <country>Pakistan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Om Parkash</last_name>
      <phone>+923333509749</phone>
      <email>om.parkash@aku.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>Pakistan</country>
  </location_countries>
  <reference>
    <citation>Poordad FF. Review article: the burden of hepatic encephalopathy. Aliment Pharmacol Ther. 2007 Feb;25 Suppl 1:3-9. doi: 10.1111/j.1746-6342.2006.03215.x.</citation>
    <PMID>17295846</PMID>
  </reference>
  <reference>
    <citation>Rahimi RS, Rockey DC. Novel Ammonia-Lowering Agents for Hepatic Encephalopathy. Clin Liver Dis. 2015 Aug;19(3):539-49. doi: 10.1016/j.cld.2015.04.008. Epub 2015 May 30.</citation>
    <PMID>26195207</PMID>
  </reference>
  <reference>
    <citation>Elkington SG, Floch MH, Conn HO. Lactulose in the treatment of chronic portal-systemic encephalopathy. A double-blind clinical trial. N Engl J Med. 1969 Aug 21;281(8):408-12. doi: 10.1056/NEJM196908212810803. No abstract available.</citation>
    <PMID>4894464</PMID>
  </reference>
  <reference>
    <citation>Sharma P, Sharma BC, Sarin SK. Predictors of nonresponse to lactulose in patients with cirrhosis and hepatic encephalopathy. Eur J Gastroenterol Hepatol. 2010 May;22(5):526-31. doi: 10.1097/MEG.0b013e3283341b7d.</citation>
    <PMID>20009938</PMID>
  </reference>
  <reference>
    <citation>Tapper EB, Jiang ZG, Patwardhan VR. Refining the ammonia hypothesis: a physiology-driven approach to the treatment of hepatic encephalopathy. Mayo Clin Proc. 2015 May;90(5):646-58. doi: 10.1016/j.mayocp.2015.03.003. Epub 2015 Apr 9.</citation>
    <PMID>25865476</PMID>
  </reference>
  <reference>
    <citation>Romero-Gomez M, Jover M, Del Campo JA, Royo JL, Hoyas E, Galan JJ, Montoliu C, Baccaro E, Guevara M, Cordoba J, Soriano G, Navarro JM, Martinez-Sierra C, Grande L, Galindo A, Mira E, Manes S, Ruiz A. Variations in the promoter region of the glutaminase gene and the development of hepatic encephalopathy in patients with cirrhosis: a cohort study. Ann Intern Med. 2010 Sep 7;153(5):281-8. doi: 10.7326/0003-4819-153-5-201009070-00002.</citation>
    <PMID>20820037</PMID>
  </reference>
  <reference>
    <citation>Jain L, Sharma BC, Sharma P, Srivastava S, Agrawal A, Sarin SK. Serum endotoxin and inflammatory mediators in patients with cirrhosis and hepatic encephalopathy. Dig Liver Dis. 2012 Dec;44(12):1027-31. doi: 10.1016/j.dld.2012.07.002. Epub 2012 Aug 9.</citation>
    <PMID>22883217</PMID>
  </reference>
  <reference>
    <citation>Wijdicks EF. Hepatic Encephalopathy. N Engl J Med. 2016 Oct 27;375(17):1660-1670. doi: 10.1056/NEJMra1600561. No abstract available.</citation>
    <PMID>27783916</PMID>
  </reference>
  <reference>
    <citation>Zuberi BF, Alvi H, Zuberi FF, Rasheed T, Nawaz Z, Fatima-Tuz-Zohra. Frequency of minimal hepatic encepalopathy in illeterate patients with compensated cirrhosis. Pak J Med Sci. 2016 May-Jun;32(3):595-8. doi: 10.12669/pjms.323.9655.</citation>
    <PMID>27375696</PMID>
  </reference>
  <reference>
    <citation>Gerber T, Schomerus H. Hepatic encephalopathy in liver cirrhosis: pathogenesis, diagnosis and management. Drugs. 2000 Dec;60(6):1353-70. doi: 10.2165/00003495-200060060-00008.</citation>
    <PMID>11152016</PMID>
  </reference>
  <reference>
    <citation>Gluud LL, Vilstrup H, Morgan MY. Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2016 May 6;2016(5):CD003044. doi: 10.1002/14651858.CD003044.pub4.</citation>
    <PMID>27153247</PMID>
  </reference>
  <reference>
    <citation>Williams R, Bass N. Rifaximin, a nonabsorbed oral antibiotic, in the treatment of hepatic encephalopathy: antimicrobial activity, efficacy, and safety. Rev Gastroenterol Disord. 2005;5 Suppl 1:S10-8.</citation>
    <PMID>15976747</PMID>
  </reference>
  <reference>
    <citation>Kimer N, Krag A, Moller S, Bendtsen F, Gluud LL. Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther. 2014 Jul;40(2):123-32. doi: 10.1111/apt.12803. Epub 2014 May 21.</citation>
    <PMID>24849268</PMID>
  </reference>
  <reference>
    <citation>Rahimi RS, Singal AG, Cuthbert JA, Rockey DC. Lactulose vs polyethylene glycol 3350--electrolyte solution for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial. JAMA Intern Med. 2014 Nov;174(11):1727-33. doi: 10.1001/jamainternmed.2014.4746.</citation>
    <PMID>25243839</PMID>
  </reference>
  <reference>
    <citation>Rockey DC, Vierling JM, Mantry P, Ghabril M, Brown RS Jr, Alexeeva O, Zupanets IA, Grinevich V, Baranovsky A, Dudar L, Fadieienko G, Kharchenko N, Klaryts'ka I, Morozov V, Grewal P, McCashland T, Reddy KG, Reddy KR, Syplyviy V, Bass NM, Dickinson K, Norris C, Coakley D, Mokhtarani M, Scharschmidt BF; HALT-HE Study Group. Randomized, double-blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy. Hepatology. 2014 Mar;59(3):1073-83. doi: 10.1002/hep.26611.</citation>
    <PMID>23847109</PMID>
  </reference>
  <reference>
    <citation>American Association for the Study of Liver Diseases; European Association for the Study of the Liver. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol. 2014 Sep;61(3):642-59. doi: 10.1016/j.jhep.2014.05.042. Epub 2014 Jul 8. No abstract available. Erratum In: J Hepatol. 2015 Oct;63(4):1055.</citation>
    <PMID>25015420</PMID>
  </reference>
  <reference>
    <citation>Gluud LL, Vilstrup H, Morgan MY. Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2016 Apr 18;4:CD003044. doi: 10.1002/14651858.CD003044.pub3.</citation>
    <PMID>27089005</PMID>
  </reference>
  <reference>
    <citation>Shehata HH, Elfert AA, Abdin AA, Soliman SM, Elkhouly RA, Hawash NI, Soliman HH. Randomized controlled trial of polyethylene glycol versus lactulose for the treatment of overt hepatic encephalopathy. Eur J Gastroenterol Hepatol. 2018 Dec;30(12):1476-1481. doi: 10.1097/MEG.0000000000001267.</citation>
    <PMID>30234645</PMID>
  </reference>
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    <citation>Naderian M, Akbari H, Saeedi M, Sohrabpour AA. Polyethylene Glycol and Lactulose versus Lactulose Alone in the Treatment of Hepatic Encephalopathy in Patients with Cirrhosis: A Non-Inferiority Randomized Controlled Trial. Middle East J Dig Dis. 2017 Jan;9(1):12-19. doi: 10.15171/mejdd.2016.46.</citation>
    <PMID>28316761</PMID>
  </reference>
  <reference>
    <citation>Friedman S, Schiano T. Cirrhosis and its sequelae. Cecil Textbook of Medicine 22nd ed Philadelphia, Pa: Saunders. 2004:936-44.</citation>
  </reference>
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    <citation>American College of R. Expert Panel on Gastrointestinal Imaging. Liver lesion characterization Reston, Va: American College of Radiology. 2002.</citation>
  </reference>
  <reference>
    <citation>Hassanein TI, Hilsabeck RC, Perry W. Introduction to the Hepatic Encephalopathy Scoring Algorithm (HESA). Dig Dis Sci. 2008 Feb;53(2):529-38. doi: 10.1007/s10620-007-9895-0. Epub 2007 Aug 21.</citation>
    <PMID>17710551</PMID>
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    <citation>Lee WM, Stravitz RT, Larson AM. Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. Hepatology. 2012 Mar;55(3):965-7. doi: 10.1002/hep.25551. No abstract available.</citation>
    <PMID>22213561</PMID>
  </reference>
  <reference>
    <citation>Mendez-Sanchez N, Aguilar-Ramirez JR, Reyes A, Dehesa M, Juorez A, Castneda B, Sanchez-Avila F, Poo JL, Guevara Gonzalez L, Lizardi J, Valdovinos MA, Uribe M, Contreras AM, Tirado P, Aguirre J, Rivera-Benitez C, Santiago-Santiago R, Bosques-Padilla F, Munoz L, Guerroro A, Ramos M, Rodriguez-Hernandez H, Jacobo-Karam J; Grupo de Estudio, Asociacion Mexicana de Hepatologia. Etiology of liver cirrhosis in Mexico. Ann Hepatol. 2004 Jan-Mar;3(1):30-3.</citation>
    <PMID>15118577</PMID>
  </reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>May 23, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>April 18, 2023</last_update_submitted>
  <last_update_submitted_qc>April 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Aga Khan University</investigator_affiliation>
    <investigator_full_name>Om Parkash</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatic Encephalopathy</mesh_term>
    <mesh_term>Brain Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lactulose</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Combined data, relevant to the study publication will be made available</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04436601
org study id: 191002MED
nct id: NCT04436601
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
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.
measure: Resolution of Hepatic Encephalopathy
time frame: Change in HESA score at 24 hours, 48 hours and if applicable, 72 hours of drug administration
description: 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
measure: Mean Length of inpatient stay in hours
time frame: at time of patient discharge, an average of 72 hours
description: Duration of hospital stay will be recorded in hours
measure: 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
description: Patient will be asked at 3 month follow up if there was any other readmission anywhere with Hepatic Encephalopathy
arm group label: Lactulose
arm group type: Active Comparator
description: 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.
arm group label: PEG: Polyethylene Glycol
arm group type: Experimental
description: 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 type: Drug
intervention name: Polyethylene Glycols
description: Polyethylene glycol will be administered to half of the study patients, and their response recorded and compared with that of the Lactulose arm.
arm group label: PEG: Polyethylene Glycol
intervention type: Drug
intervention name: Lactulose
description: Lactulose (standard of care) will be administered to half of the study patients and their response recorded.
arm group label: Lactulose
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Om Parkash
role: Principal Investigator
affiliation: Aga Khan University
last name: Om Parkash
phone: +923333509749
email: om.parkash@aku.edu
last name: Asra tus Saleha Siddiqui
phone: +923323262516
email: asra.siddiqui@aku.edu
facility: 
status: Recruiting
contact: 
country: Pakistan
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responsible party type: Principal Investigator
investigator affiliation: Aga Khan University
investigator full name: Om Parkash
investigator title: Assistant Professor
mesh term: Hepatic Encephalopathy
mesh term: Brain Diseases
mesh term: Lactulose
sharing ipd: No
ipd description: Combined data, relevant to the study publication will be made available