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

NCT ID: NCT06355726

Last Updated: 2024-06-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-09
• Study Completion Date: 2025-02-28

Brief Summary

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.

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.

Conditions

Alcoholic Hepatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PLEX with SMT

3 sessions to 5 max, alternate day with SMT

Group Type: EXPERIMENTAL

Plasma Exchange

Intervention Type: BIOLOGICAL

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

Standard Medical Treatment

Intervention Type: OTHER

Standard Medical Treatment

SMT

High calorie intake 35 to 40 Kcal/kg, protein 1.2 to 1.5 g/kg,albumin,antibiotics as required

Group Type: ACTIVE_COMPARATOR

Standard Medical Treatment

Intervention Type: OTHER

Standard Medical Treatment

Interventions

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

Intervention Type: BIOLOGICAL

Standard Medical Treatment

Standard Medical Treatment

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Liver and Biliary Sciences, India

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institute of Liver & Biliary Sciences (ILBS)

New Delhi, National Capital Territory of Delhi, India

Site Status: RECRUITING

Countries

India

Central Contacts

Dr Jitendra Kumar Singh, MD

Role: CONTACT

jitendra2602kc@gmail.com

01146300000

Facility Contacts

Dr Jitendra Kumar Singh, MD

Role: primary

jitendra2602kc@gmail.com

01146300000

Other Identifiers

ILBS-Alcoholic Hepatitis-03

Identifier Type: -

Identifier Source: org_study_id