N-ACetylcysteine to Reduce Infection and Mortality for Alcoholic Hepatitis

Phase 3

Recruiting

• Conditions: Alcoholic Hepatitis; Infection
• Interventions: Drug: N-acetyl cysteine (NAC)

• Registration Number: NCT03069300
• Lead Sponsor: Imperial College London

Brief Summary

Recent data have suggested that monocyte oxidative burst defect is associated with the development of infection in patients with severe alcoholic hepatitis. One report found reduced 28 day mortality in patients treated with N-acetylcysteine combined with prednisolone when compared to prednisolone alone. The current study seeks to reveal whether the mechanism by which NAC reduces susceptibility to infection is through improvement of phagocyte oxidative burst.

Detailed Description

Randomised controlled trial, open label.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study Start: 2015-10-01
• Study First Submitted: 2017-02-28
• Study First Submitted QC: 2017-02-28
• Study First Posted: 2017-03-03
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-08
• Last Update Posted: 2021-11-09
• Primary Completion: 2022-04-01
• Study Completion: 2025-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

• Aged 18 years or older

• Clinical alcoholic hepatitis:

  • Serum bilirubin >80umol/L
  • History of alcohol excess (>80g/day male, >60g/day female)
  • Less than 4 weeks since admission to hospital
  • Maddrey's discriminant function (DF) >32
  • Informed consent

Read More

Exclusion Criteria

• Alcohol abstinence of >6 weeks prior to randomisation

• Duration of jaundice >3 months

• Other causes of liver disease including:

  • Evidence of viral hepatitis (hepatitis B or C)
  • Biliary obstruction
  • Hepatocellular carcinoma

• Evidence of current malignancy (except non-melanotic skin cancer)

• Previous entry into the study

• Patients with known hypersensitivity or previous reactions to NAC

• Pregnant or lactating women

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
prednisolone+NAC	N-acetyl cysteine (NAC)	40mg prednisolone once a day for 28 days and 30 minutes of intravenous NAC at 150mg/kg in 250ml 5% dextrose solution followed by 4 hours of intravenous NAC at 50mg/kg in 500ml 5% dextrose solution, followed by 16 hours of intravenous NAC at 100 mg/kg in 1000ml 5% dextrose solution, followed by 4 days of intravenous NAC at 100mg/kg/day in 1000ml 5% dextrose solution

Primary Outcome Measures

Name	Time	Method
Improvement in monocyte oxidative burst	24 hours
Improvement in ex vivo monocyte oxidative burst	5 days

Secondary Outcome Measures

Name	Time	Method
Proportion of patients infected	90 days	Infection will be defined in two ways: i. by new/change in intravenous antibiotic prescription and ii. published clinical and microbiological criteria for infection in the setting of liver disease
Death	90 days

Trial Locations

Locations (1)

St Mary's Hospital, Imperial College; 🇬🇧 London, United Kingdom