NCT03069300

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
42

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Oct 2015

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2015

Completed
1.4 years until next milestone

First Submitted

Initial submission to the registry

February 28, 2017

Completed
3 days until next milestone

First Posted

Study publicly available on registry

March 3, 2017

Completed
5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2022

Completed
3.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2025

Completed
Last Updated

November 9, 2021

Status Verified

November 1, 2021

Enrollment Period

6.5 years

First QC Date

February 28, 2017

Last Update Submit

November 8, 2021

Conditions

Alcoholic HepatitisInfection

Outcome Measures

Primary Outcomes (2)

  • Improvement in monocyte oxidative burst

    24 hours

  • Improvement in ex vivo monocyte oxidative burst

    5 days

Secondary Outcomes (4)

  • Proportion of patients infected

    28 days

  • Proportion of patients infected

    90 days

  • Death

    28 days

  • Death

    90 days

Study Arms (2)

prednisolone+NAC

EXPERIMENTAL

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

Drug: N-acetyl cysteine (NAC)

prednisolone

NO INTERVENTION

40mg prednisolone for 28 days

Interventions

N-acetyl cysteine (NAC)DRUG
Also known as: NAC
prednisolone+NAC

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

St Mary's Hospital, Imperial College

London, W2 1NY, United Kingdom

RECRUITING

Related 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.

    PMID: 22070475BACKGROUND

  • 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.

    PMID: 26860769RESULT

MeSH Terms

Conditions

Hepatitis, AlcoholicInfections

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

HepatitisLiver DiseasesDigestive System DiseasesLiver Diseases, AlcoholicAlcohol-Induced DisordersAlcohol-Related DisordersSubstance-Related DisordersChemically-Induced Disorders

Intervention Hierarchy (Ancestors)

CysteineAmino Acids, SulfurSulfur CompoundsOrganic ChemicalsAmino AcidsAmino Acids, Peptides, and Proteins

Study Officials

  • Mark Thursz, MD

    Imperial College London

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Nikhil Vergis, PhD

CONTACT

nvergis@ic.ac.uk

Mark Thursz, MD

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: randomized controlled trial
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 28, 2017

First Posted

March 3, 2017

Study Start

October 1, 2015

Primary Completion

April 1, 2022

Study Completion

June 1, 2025

Last Updated

November 9, 2021

Record last verified: 2021-11

Data Sharing

IPD Sharing
Will share

contact investigators

Locations

GB(1)