Condition or disease | Intervention/treatment | Phase |
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Hepatic Encephalopathy Acute-On-Chronic Liver Failure | Drug: PEG-3350 with Electolytes Drug: Lactulose | Phase 4 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 60 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | Open Label, randomized control trial |
Masking: | None (Open Label) |
Masking Description: | participant is randomised using a table of random numbers. |
Primary Purpose: | Treatment |
Official Title: | Therapeutic Efficacy of Oral PEG3350 Plus Lactulose Versus Lactulose Alone in Patients of Acute on Chronic Liver Failure With Overt Hepatic Encephalopathy: A Single Blind Prospective Randomized Controlled Study |
Actual Study Start Date : | May 20, 2018 |
Estimated Primary Completion Date : | May 25, 2020 |
Estimated Study Completion Date : | August 20, 2020 |
Arm | Intervention/treatment |
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Experimental: PEG+Lactulose
this arm will recieve PEG3350 in addition to standard of care
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Drug: PEG-3350 with Electolytes
experimental arm will receive 2 doses of PEG3350 spaced over 12 hours after randomization to arm1. PEG as dose of 2litres (1 sachet dissolved in 2L of water) will be administered via a nasogastric tube.
Drug: Lactulose Lactulose will be given orally (30ml QID) which shall be titrated to ensure 2-3 soft stools per day
Other Name: Lactulose per orally
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Active Comparator: Lactulose alone
this arm will recieve only standard of care for management of hepatic encephlaopathy with ACLF
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Drug: Lactulose
Lactulose will be given orally (30ml QID) which shall be titrated to ensure 2-3 soft stools per day
Other Name: Lactulose per orally
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Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Syed Ahmed, MD | 9035821510 | syedusman92@gmail.com |
India | |
Postgraduate Institute of Medical Education and Research | Recruiting |
Chandigarh, India, 160012 | |
Contact: Radha K Dhiman, DM 7087009337 rkpsdhiman@hotmail.com |
Study Chair: | Madhumita Premkumar, DM | Postgraduate Institute of Medical Education and Research |
Tracking Information | |||||||
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First Submitted Date ICMJE | June 13, 2019 | ||||||
First Posted Date ICMJE | June 17, 2019 | ||||||
Last Update Posted Date | June 17, 2019 | ||||||
Actual Study Start Date ICMJE | May 20, 2018 | ||||||
Estimated Primary Completion Date | May 25, 2020 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | No Changes Posted | ||||||
Current Secondary Outcome Measures ICMJE |
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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 | PEG3350 in ACLF With Hepatic Encephalopathy | ||||||
Official Title ICMJE | Therapeutic Efficacy of Oral PEG3350 Plus Lactulose Versus Lactulose Alone in Patients of Acute on Chronic Liver Failure With Overt Hepatic Encephalopathy: A Single Blind Prospective Randomized Controlled Study | ||||||
Brief Summary | it is a single blind randomised control study which aims to study the effect of PEG3350 in resolution of overt hepatic encephalopathy in patients of acute on chronic liver failure. this will be compared with the standard of care in the management of hepatic encephalopathy. | ||||||
Detailed Description |
Therapeutic Efficacy of oral PEG3350 plus Lactulose Versus Lactulose alone in Patients of Acute on Chronic Liver Failure with Overt Hepatic Encephalopathy: A Single Blind Prospective Randomized Controlled Study INTRODUCTION: Hepatic encephalopathy (HE) refers to syndrome observed in patients with cirrhosis exhibiting clinical manifestations of mild to severe cognitive dysfunction (neuropsychiatric abnormalities) characterised by alterations in sleep pattern, sudden behavioural changes & personality changes along with altered cognition, or coma. The basic pathophysiology involved in development of potentially reversible neuropsychiatric abnormalities associated with HE are not clearly understood but ammonia generation by gut microbiota is considered as significant contributing factor. HE is categorized into overt hepatic encephalopathy (OHE) and minimal hepatic encephalopathy (MHE). Previous studies have reported the incidence of OHE and MHE to be 30-45% and 60-80% respectively in patients suffering from cirrhosis . In the present study, we propose to assess the efficacy of an ammonia reducing therapy utilisisng PEG 3350 in patients with Acute on Chronic Liver Failure (ACLF). Hepatic encephalopathy in Acute on Chronic Liver Failure (ACLF) The syndrome of acute on chronic liver failure is a recently described clinical entity. The defining criterion for acute-on-chronic liver failure (ACLF) takes into consideration the existence of hepatic encephalopathy (HE) within 4 weeks. In Asia, the following definition has been suggested: "acute hepatic insult manifesting as jaundice (serum bilirubin level ≥5 mg/dl) and coagulopathy (international normalized ratio ≥1.5), complicated within 4 weeks by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease" . In the West, experts proposed to define ACLF as "an acute deterioration of liver function in patients with cirrhosis which is usually associated with a precipitating event and results in the failure of one or more organs and high short-term mortality". This definition is on the basis of the European Association for the Study of the Liver (EASL)-Chronic Liver Failure (CLIF) Consortium Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC)" study which established diagnostic criteria for ACLF in hospitalized patients who had an acute decompensation (AD) of cirrhosis . In ACLF, hyperammonemia, systemic inflammatory state mediated by various cytokines which includes sepsis/SIRS, bacterial translocation, insulin resistance resulting in hyperglycemia and oxidant induced injury, in addition modulation by glutaminase gene alteration along with alterations in cerebral hemodynamics appear to be crucial factors in the pathogenesis of encephalopathy.Various studies have explored the potential of bacterial infections, hyponatremia, alcohol intake and factors responsible for systemic inflammation in HE. HE is diagnosed after excluding other causes of altered cognition such as metabolic, neurological and psychiatric conditions. Clinical features of HE in ACLF patients are very much similar to those with HE in acute liver failure (ALF). The clear correlation of serum ammonia levels, systemic inflammation and outcome of HE in ACLF patients is not well understood . Factors precipitating, HE, such as constipation, hyponatremia, infections etc. must be promptly identified and addressed appropriately. Currently Evidence-based medicine approach for the management of HE is restricted to early bowel evacuation and administration of non-absorbable antibiotics such as rifaximin. Antibiotics, prebiotics, treatment of diabetes and other supportive management reduces the systemic inflammation . Most of the therapy regimens in treatment of hepatic encephalopathy are directed towards reduction of the generation of nitrogenous products, for which gut is the major site of generation and the organ of accumulation of nitrogenous toxins especially Ammonia in patients with liver failure and portosystemic shunting Treatment of Hepatic Encephalopathy Lactulose (beta-1,4-galactosido-fructose) has been used in practice for the management of HE because of its ammonia lowering effects . The mechanism by which lactulose act still remains controversial and is hypothesized to be by following methods, first is metabolism of lactulose by gut bacteria release organic acids which play vital role in trapping ammonium ions, second is by elimination of ammonia generating organisms and third is by replacing amminogenic organisms with urease lacking acidophilic bacteria . The role of inhibition of glutamine followed by decreased ammonia genesis has also been considered. Management and treatment of patients with OHE is mainly focused on elimination of underlying precipitating factors, nutritional supports, and lowering ammonemia . Lactulose and rifaximin are the most widely used medications to lower ammonia generation; however, their exact mechanism of action is still not well understood . REVIEW OF LITERATURE: Proposed Role of PEG 3350 in HE Before the routine use of non-absorbable disaccharides, simple laxatives were used in the management of hepatic encephalopathy assuming the beneficial effects of bowel evacuation in resolution of neurocognitive disturbances in liver diseases. With this principle, there were trials done assessing the clinical benefits of PEG solution, which is a commonly used laxative is used routinely in bowel preparation for colonoscopy. Currently there is a significant data showing the beneficial effects of PEG 3350 in overt HE due to underlying cirrhosis, however its efficacy in ACLF remains to be looked into. Similar to lactulose, polyethylene glycol is unabsorbed from the gut but in addition it also lacks the unabsorbed carbohydrate load which aids in lowering of stool pH and enhancing the amount of water lost from the stools. Furthermore, the rate of ammonia excretion via feces is enhanced with PEG as compared to lactulose. In this study, we propose to evaluate the efficacy & safety profile of PEG3350 plus lactulose vs. lactulose alone for treatment of ACLF. An essential understanding required with PEG usage is to consider that it exerts a significant cathartic effect and thus may progress to dehydration, hypovolemia, dyselectrolemia, and even blood gas abnormalities. It's also the most prominently used preparative agent in patients undergoing colonoscopy, and is thus widely used in human population worldwide. PEG preparations are easily available and are cost effective. Another potential benefit of utilizing PEG for OHE is that it may result in decrease in the duration of hospitalization, depending on the causes of the HE. By accelerating the treatment of hepatic encephalopathy, PEG can help patients to return to normal life more rapidly and decrease the direct and indirect cost of illness caused by hepatic encephalopathy. PEG, which resolves decreased level of consciousness more effectively and more rapidly in the first 24 hours, can also help physicians to identify the other causes of altered mental status more quickly and more accurately. Some of the trials which have compared the efficacy of PEG in management of HE are: Author Trial Conclusion. Rahimi et al., (n=50) "Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution for Treatment of Overt Hepatic Encephalopathy The HELP Randomized Clinical Trial" "PEG led to more rapid HE resolution than standard therapy". Naderian et al., (n=40) "Polyethylene Glycol and Lactulose versus Lactulose Alone in the Treatment of Hepatic Encephalopathy in Patients with Cirrhosis: A Non-Inferiority Randomized Controlled Trial" "The use of PEG along with lactulose in comparison with lactulose alone is more effective in the treatment of hepatic encephalopathy in patients with cir¬rhosis". Patients and methods: Study Design: A prospective interventional cohort study using the drug PEG3350 + lactulose versus lactulose alone. Allocation: randomized Intervention model: parallel assignment Masking: none, open label Primary purpose: treatment. Setting: Academic hospital - PGI (Chandigarh, India). Patients fulfilling eligibility criteria will be approached for informed written consent. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 4 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: Open Label, randomized control trial Masking: None (Open Label)Masking Description: participant is randomised using a table of random numbers. Primary Purpose: Treatment
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Unknown status | ||||||
Estimated Enrollment ICMJE |
60 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | August 20, 2020 | ||||||
Estimated Primary Completion Date | May 25, 2020 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 75 Years (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | India | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03987893 | ||||||
Other Study ID Numbers ICMJE | INT/IEC/2018-000485 | ||||||
Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Radha K Dhiman, Postgraduate Institute of Medical Education and Research | ||||||
Study Sponsor ICMJE | Postgraduate Institute of Medical Education and Research | ||||||
Collaborators ICMJE | Not Provided | ||||||
Investigators ICMJE |
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PRS Account | Postgraduate Institute of Medical Education and Research | ||||||
Verification Date | June 2019 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |