Efficacy of Plasma Exchange Therapy vs Standard Medical Therapy in Severe Alcoholic Hepatitis With High Discriminant Function

Efficacy of Plasma Exchange Therapy vs Standard Medical Therapy in Severe Alcoholic Hepatitis With High Discriminant Function : A Randomised Controlled Trial

Alcoholic hepatitis, the most florid form of alcoholic liver disease, has a very high short-term mortality of up to 50% and no specific therapies are available other than steroids. Steroids also only show a limited utility in improving the short-term survival and boast no evidence of any long-term benefits. Additionally, only a small proportion of patients with alcoholic hepatitis are eligible to receive steroids. Thus, a large number of patients are either not eligible or do not respond to steroids and this group outnumbers those who do respond to steroids, leaving us without any specific therapeutic options for a majority of these individuals.[1] Even liver transplantation is not feasible in most cases due to the presence of sepsis or recent alcohol consumption and many ethical and logistic issues are involved despite the documented safety and survival benefits of early liver transplantation in patients with severe alcoholic hepatitis (SAH) not responding to medical management.[2,8] Therefore, newer, more effective, and nontransplant therapeutic options for managing severe alcoholic hepatitis are needed. TPE is expected to be an effective and well-tolerated bridge therapy in patients with severe alcoholic hepatitis of moderate severity not improving on SMT and without immediate prospects for liver transplantation.

Study Overview

• Status: Not yet recruiting
• Conditions: Alcoholic Hepatitis
• Intervention / Treatment: Other: Standard Medical Treatment; Biological: Plasma Exchange

Detailed Description

Hypothesis:wehypothesise that the early treatment with therapeutic plasma exchange in alcoholic hepatitis patients might improve overall survival in carefully selected patients by removing cytokines, chemokines and toxic substances.

Aim:

To compare transplant free survival between plasma exchange therapy and standard medical therapy in severe alcoholic hepatitis

Methodology:

Severe alcoholic hepatitis will be screened for the study and will be managed with SMT initially will be assessed for steroid therapy if becomes ineligible counselled for liver transplant in view of high DF and MELD ,if there is no options of Liver transplant in near future ,1 month will be given option for PLEX but it will be decided by randomisation whether he will get SMT or PLEX.He/she will also be told that PLEX is not a approved treatment and is a trial therapy and they may or may not get benefited.Patients Patients who agreed to undergo PLEX then undergo randomisation between PLEX and SMT and allocated in either group accordingly.

Control group will be administered SMT only.Case are those who get both SMT and PLEX. SMT involved empirical antibiotics as per treating physician,multivitamins,albumin. Hepatic encephalopathy (HE) will be treated with lactulose and rifaximin. Ascites with diuretics if not contraindicated because of renal insufficiency or HE. All patients will receive salt restricted, high protein diet (1.5 g/kg of proteins) either enterally/parenterally in addition to thiamine and multivitamins,35 to 45 kcal /kg .

Cases will be administered SMT with Plasma exchange session which will be done on alternate day to a maximum of 5 sessions. PLEX will be discontinued if the patients Shows sustained clinical improvement, Receive liver transplantation, Refuses further PLEX session,no improvement in clinical condition and Intolerant to PLEX procedure

Study population:

• Age - 18-60 years
• Patients with steroid ineligible(DF > 80< 120,MELD > 30) severe alcoholic hepatitis(Bili > 5 ,INR > 1.5)

Study design: Randomised controlled study done at Department of Hepatology,Institute of Liver and Biliary Sciences,NewDelhi,India.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr Jitendra Kumar Singh, MD; Phone Number: 01146300000; Email: jitendra2602kc@gmail.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver & Biliary Sciences (ILBS)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 to 60 years
2. Severe alcoholic hepatitis with DF>80< 120 or MELD >30
3. No liver transplant option available in near future(for atleast 1 month)
4. Patient able to bear the cost of Plasma exchange by himself/herself

Exclusion Criteria:

1. Active sepsis
2. S creatinine >1.5mg/dl
3. Chronic kidney disease
4. Pregnancy
5. HCC or any other malignancy
6. Active Bleeding
7. Allergic to replacement fluid (FFP) in TPE
8. Severe Hypocalcemia (<7.6 mg/dl)
9. Failure to give consent
10. Financial issues to bear cost of Plasma exchange

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PLEX with SMT; 3 sessions to 5 max, alternate day with SMT	Other: Standard Medical Treatment; Standard Medical Treatment; Biological: Plasma Exchange; Plasma exchange session will be done on alternate day to a maximum of 5 sessions. PLEX will be discontinued if the patients Shows sustained clinical improvement, Receive liver transplantation, Refuses further PLEX session,no improvement in clinical condition and Intolerant to PLEX procedure
Active Comparator: SMT; High calorie intake 35 to 40 Kcal/kg, protein 1.2 to 1.5 g/kg,albumin,antibiotics as required	Other: Standard Medical Treatment; Standard Medical Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Liver transplant free survival at 28 days, 90 days and 180 days.	28 days, 90 days and 180 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in total bilirubin and INR as measured by Discriminant Functions	28 days, 90 days and 180 days
Number of patients with change in Model for End Stage Liver Disease (MELD)	28 days, 90 days and 180 days
Number of patients with change in CTP	28 days, 90 days and 180 days
Number of patients with change in LSM,SSM	28 days, 90 days and 180 days
Mortality in both groups	28 days, 90 days and 180 days
clinical improvement in the form of jaundice as measured by total bilirubin	28 days, 90 days and 180 days
clinical improvement in the form of hepatic encephalopathy as measured by west haven criteria	28 days, 90 days and 180 days
clinical improvement in the form of ascites as measured by ICA criteria.	28 days, 90 days and 180 days
Frequency of decompensation events on follow up period	28 days, 90 days and 180 days
Adverse events during plasma exchange	28 days

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2024
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): February 28, 2025

Study Registration Dates

• First Submitted: March 4, 2024
• First Submitted That Met QC Criteria: April 3, 2024
• First Posted (Actual): April 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Alcohol-Related Disorders; Substance-Related Disorders; RNA Virus Infections; Virus Diseases; Infections; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Hepatitis; Hepatitis A; Hepatitis, Alcoholic
• Other Study ID Numbers: ILBS-Alcoholic Hepatitis-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No