Clinical trial NCT03069300: N-ACetylcysteine to Reduce Infection and Mortality for Alcoholic Hepatitis
Official title: The Mechanism of Action of N-acetylcysteine for Reducing the Risk of Infection in Alcoholic Hepatitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Alcoholic Hepatitis
Infection
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2017-03-03
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized controlled trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Improvement in monocyte oxidative burst
timeFrame: 24 hours
measure: Improvement in ex vivo monocyte oxidative burst
timeFrame: 5 days
Secondary outcomes:
measure: Proportion of patients infected
timeFrame: 28 days
measure: Proportion of patients infected
timeFrame: 90 days
measure: Death
timeFrame: 28 days
measure: Death
timeFrame: 90 days
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: St Mary's Hospital, Imperial College
Study officials:
affiliation: Imperial College London
name: Mark Thursz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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 oxidative burst predicts infection in alcoholic hepatitis and is associated with reduced expression of NADPH oxidase. Gut. 2017 Mar;66(3):519-529. doi: 10.1136/gutjnl-2015-310378. Epub 2016 Feb 9.