N-ACetylcysteine to Reduce Infection and Mortality for Alcoholic Hepatitis

Infection Clinical Trial

— NACAH  

Official title:

The Mechanism of Action of N-acetylcysteine for Reducing the Risk of Infection in Alcoholic Hepatitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03069300
• Other study ID #: 14SM2383
• Status: Recruiting
• Phase: Phase 3
• Start date: October 1, 2015
• Est. completion date: June 1, 2025

Study information

• Verified date: November 2021
• Source: Imperial College London
• Contact: Nikhil Vergis, PhD
• Email: nvergis[@]ic.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Randomised controlled trial, open label.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: June 1, 2025
• Est. primary completion date: April 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Alcoholic Hepatitis
• Communicable Diseases
• Hepatitis
• Hepatitis A
• Hepatitis, Alcoholic
• Infection
• Infections

Intervention

Drug:
• N-acetyl cysteine (NAC)

Locations

Country	Name	City	State
United Kingdom	St Mary's Hospital, Imperial College	London

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

Nguyen-Khac E, Thevenot T, Piquet MA, Benferhat S, Goria O, Chatelain D, Tramier B, Dewaele F, Ghrib S, Rudler M, Carbonell N, Tossou H, Bental A, Bernard-Chabert B, Dupas JL; AAH-NAC Study Group. Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. N Engl J Med. 2011 Nov 10;365(19):1781-9. doi: 10.1056/NEJMoa1101214. — View Citation

Vergis N, Khamri W, Beale K, Sadiq F, Aletrari MO, Moore C, Atkinson SR, Bernsmeier C, Possamai LA, Petts G, Ryan JM, Abeles RD, James S, Foxton M, Hogan B, Foster GR, O'Brien AJ, Ma Y, Shawcross DL, Wendon JA, Antoniades CG, Thursz MR. Defective monocyte — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in monocyte oxidative burst		24 hours
Primary	Improvement in ex vivo monocyte oxidative burst		5 days
Secondary	Proportion of patients infected	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	28 days
Secondary	Proportion of patients infected	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	90 days
Secondary	Death		28 days
Secondary	Death		90 days