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

Study Overview
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Brief Summary
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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.

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

Conditions
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Drug Induced Liver Injury

Intervention / Treatment
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* Drug: Prednisolone
* Drug: N-Acetylcysteine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prednisolone + N-Acetylcysteine<br>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<br> <br> Drug: N-Acetylcysteine<br>* 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<br>|
| Active Comparator: N-Acetylcysteine<br>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<br>* 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<br>|

What is the study measuring?
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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 |