Efficacy of N-acetylcysteine With or Without Steroids in Drug Induced Liver Injury

Efficacy of N-acetylcysteine With or Without Steroids in Drug Induced Liver Injury: A Prospective Randomized Controlled Trial

Intervention - Subjects will be randomized to 2 groups

Group A - subjects will receive Prednisolone for 20 days with NAC (N-Acetylcysteine)

Group B - will receive NAC (N-Acetylcysteine) only NAC (N-acetylcysteine) dosing

Loading dose: 150 mg/kg IV; mix in 200 mL of 5% dextrose in water (D5W) and infuse over 1 hour

Dose 2: 50 mg/kg IV in 500 mL D5W over 4 h

Dose 3: 100 mg/kg IV in 1000 mL D5W over 16 h

• Monitoring and assessment-Liver Biopsy at baseline and at 3 months, Liver Function Test at regular intervals.
• Stopping rule-Development of sepsis, worsening of Liver functions.

Study Overview

• Status: Terminated
• Conditions: Drug Induced Liver Injury
• Intervention / Treatment: Drug: Prednisolone; Drug: N-Acetylcysteine

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of liver and Biliary Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients with severe DILI (Drug Induced Liver Injury)
• Age more than or equal to 18 years

Exclusion Criteria:

• Patients with HAV (Hepatitis A Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus), HEV (Hepatitis E Virus) Positive
• Patients with sepsis
• AMA positive
• Low Ceruloplasmin
• Transferrin saturation >45%
• Patients with Cirrhosis
• Patients with h/o jaundice prior to the intake of drug

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: Prednisolone + N-Acetylcysteine; Prednisolone for 20 days with NAC (N-Acetylcysteine) NAC (N-Acetylcysteine) dosing-Loading dose: 150 mg/kg IV; mix in 200 mL of 5% dextrose in water (D5W) and infuse over 1 h Dose 2: 50 mg/kg IV in 500 mL D5W over 4 h Dose 3: 100 mg/kg IV in 1000 mL D5W over 16 h	Drug: Prednisolone; Drug: N-Acetylcysteine; NAC (N-Acetylcysteine) dosing-Loading dose: 150 mg/kg IV; mix in 200 mL of 5% dextrose in water (D5W) and infuse over 1 h Dose 2: 50 mg/kg IV in 500 mL D5W over 4 h Dose 3: 100 mg/kg IV in 1000 mL D5W over 16 h
Active Comparator: N-Acetylcysteine; NAC (N-Acetylcysteine) dosing-Loading dose: 150 mg/kg IV; mix in 200 mL of 5% dextrose in water (D5W) and infuse over 1 h Dose 2: 50 mg/kg IV in 500 mL D5W over 4 h Dose 3: 100 mg/kg IV in 1000 mL D5W over 16 h	Drug: N-Acetylcysteine; NAC (N-Acetylcysteine) dosing-Loading dose: 150 mg/kg IV; mix in 200 mL of 5% dextrose in water (D5W) and infuse over 1 h Dose 2: 50 mg/kg IV in 500 mL D5W over 4 h Dose 3: 100 mg/kg IV in 1000 mL D5W over 16 h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with normalization of LFT (Liver Function Test) in both groups.	Normalization of LFT (Liver Function Test) which is defined as Total bilirubin within normal limits.	20 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in of Histology.	Improvement is defined as decrease in inflammation, decrease in cholestasis.	20 days
Improvement in CBC profile	Improvement is defined normalization of CBC profile.	20 days
Improvement in coagulation profile	Improvement is defined normalization of Coagulation profile.	20 days
Improvement in KFT profile	Improvement is defined normalization of KFT profile.	20 days
Proportion of patients develop adverse effects in both groups.		20 days

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India
• Investigators: Principal Investigator: Dr Anand Kulkarni V, MD, Institute of liver and Biliary Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): August 31, 2016
• Study Completion (Actual): August 31, 2016

Study Registration Dates

• First Submitted: February 8, 2016
• First Submitted That Met QC Criteria: February 18, 2016
• First Posted (Estimate): February 19, 2016

Study Record Updates

• Last Update Posted (Actual): December 18, 2017
• Last Update Submitted That Met QC Criteria: December 15, 2017
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Liver Diseases; Drug-Related Side Effects and Adverse Reactions; Poisoning; Wounds and Injuries; Chemical and Drug Induced Liver Injury; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Prednisolone; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: ILBS-DILI-001