Role of Extended Low Dose Prednisolone in Achieving Clinical and Biochemical Remission in Steroid Responsive Severe Alcoholic Hepatitis

Role of Extended Low Dose Prednisolone in Achieving Clinical and Biochemical Remission in Steroid Responsive Severe Alcoholic Hepatitis.

Severity of alcoholic hepatitis is defined by Maddrey's discriminant function, value of 32 or higher indicates severe alcoholic hepatitis that carries an adverse prognosis with one month mortality of 30%-50%. Prednisolone (40 mg/day) given orally should be considered to improve 28-day mortality in patients with severe AH. Abstinence is key to long-term survival.

According to current protocol, we discontinue the treatment after 28 days but only 15 % patient is achieving the DF < 32 after 28 days of treatment.

The aim of this study is to evaluate the role of extended low dose prednisolone (10mg) in achieving remission by day-90 in steroid responsive severe alcoholic hepatitis.

Study Overview

• Status: Not yet recruiting
• Conditions: Severe Alcoholic Hepatitis
• Intervention / Treatment: Drug: Placebo; Drug: Prednisolone; Other: Standard Medical therapy

Detailed Description

Study Design- Single center, Open label, Randomized controlled trial

• According to current protocol, we discontinue the treatment after 28 days, it improve the mortality rate in severe alcoholic patient with mDF score of more than 32 but only 15% patient is achieving the mDF < 32 after 28 days of treatment.
• Abstinence is key to long-term survival. No data is available in giving steroids for more than 28days going to improve clinical or biochemical parameter of the patient.

Methodology:

• Study population: All patients aged ≥ 18 years and ≤ 60 years admitted in Institute of Liver and Biliary Sciences, New Delhi with Severe Alcoholic hepatitis mDF of more than 32 days after 28days of steroid therapy and are giving written consent for participation in the study. Option of LDLT, Plasma exchange, FMT, GM- CSF given to patient with DF more than 32 after 28 days of steroid therapy and these patients are excluded from the study.
• Study period - 1.5 years after IEC approval
• Sample size - We are enrolling 150 patients.- Assuming that the response rate is 50% in prednisolone + SMT group and 20% in only SMT group. With alpha- 5% and power of 80, we need to enroll - 90 cases i.e, 45 in each group. Further adding 10% drop out cases, it was decided to enroll 100 patients i.e, 50 in each group. Allocation will be done randomly by block randomization panel by block size of 10. Further assuming that DF > 32 will be in 80% cases we need to enroll 125 cases. Further 80% will have lille score < 0.45, so it is to decide to enroll 150 cases.
• Intervention - Extended steroid group: 10mg of prednisolone plus standard medical therapy for 60 days.
• Placebo group: Standard treatment plus placebo that the patient would receive included in the trial.
• SMT- IV Albumin, Diuretics, Multi vitamins as per clinicians decision
• Monitoring and assessment:

• Investigations - Tests performed on Day 0, 4, 7, 28, 60 and 90.

  • Routine: CBC, RFT, LFT, PT/INR, CXR, PCT, Urine R/M & C/S, Blood C/S,
  • Blood sugar- fasting & PP.
• Statistical Analysis: The data will be represented as mean ± SD. The categorical data will be analysed using Chi-square test. The continuous data will be analysed by student T test, or Mann-Whitney test, whichever is applicable. Besides this, Cox regression will be applied to analyse the variables. For all tests, p≤ 0.05 will be considered statistically significant
• Adverse effects
• New onset Diabetes, risk of infection
• Stopping rule
• Discontinuation of steroids (variceal bleed, infections, uncontrolled sugars, new onset AKI)
• Death
• Liver transplantation
• Lapse or relapse of alcohol consumption

Expected outcome of the project:

- Improvement in the mDF score (<32) i.e. Remission in severe alcoholic hepatitis.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr Ravi Nishad, MD; Phone Number: 01146300000; Email: ravinishad.422@gmail.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver & Biliary Sciences (ILBS)
      • Contact: Dr Ravi Nishad, MD; Phone Number: 01146300000; Email: ravinishad.422@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Persistence of mDF > 32 at day 28 of steroids.

Exclusion Criteria:

1. Active infection
2. Uncontrolled sugars
3. No consent

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: Extended Steroid Therapy; 10mg of prednisolone plus standard medical therapy for 60 days. SMT- IV Albumin, Diuretics, Multi vitamins as per clinicians decision	Drug: Prednisolone; 10mg of prednisolone plus standard medical therapy for 60 days; Other: Standard Medical therapy; IV Albumin, Diuretics, Multi vitamins as per clinicians decision
Active Comparator: Placebo group; Standard treatment plus placebo that the patient would receive included in the trial. SMT- IV Albumin, Diuretics, Multi vitamins as per clinicians decision	Drug: Placebo; Placebo; Other: Standard Medical therapy; IV Albumin, Diuretics, Multi vitamins as per clinicians decision

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess the proportion of steroid responsive SAH patients achieving remission by extended low dose Prednisolone (10mg/day) till day 90 in comparison to SMT	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the liver disease severity parameters like CTP, MELD-Na, DF, by extending the low dose steroids by 2 months in the study group compared with the control group.		90 days
Number of patients with SAH achieving 90 day transplant-free survival between the two groups.		90 day, 180 day
New onset infections, diabetes	To check new onset of infection as suspected by clinical presentation and by laboratory tests such as procalcitonin, Urine Culture, Blood Culture, chest X- Ray and Ascitic fluid analysis. And for measuring diabetes onset regular fasting and post prandial sugar charting on weekly basis throughout the study period.	90 days
90 day readmission rates		90 days

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Estimated): November 25, 2023
• Primary Completion (Estimated): February 27, 2025
• Study Completion (Estimated): February 27, 2025

Study Registration Dates

• First Submitted: November 16, 2023
• First Submitted That Met QC Criteria: December 2, 2023
• First Posted (Estimated): December 4, 2023

Study Record Updates

• Last Update Posted (Estimated): December 4, 2023
• Last Update Submitted That Met QC Criteria: December 2, 2023
• Last Verified: October 1, 2023

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; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisolone
• Other Study ID Numbers: ILBS-ALD-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