Alcoholic HepatitisPhase 3NACAHNCT03069300
N-ACetylcysteine to Reduce Infection and Mortality for Alcoholic Hepatitis
A Phase 3 study testing N-acetyl cysteine (NAC) in people with Alcoholic Hepatitis and Infection, run by Imperial College London at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alcoholic Hepatitis, Infection
- What is being tested?
- N-acetyl cysteine (NAC)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Oct 2015to 1 Jun 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Nikhil Vergis, PhD contact
Mark Thursz, MD contact
United Kingdom1 site, 1 recruiting
- Recruiting
St Mary's Hospital, Imperial College
London, W2 1NY
Nikhil Vergis, PhD
About this study
Official title: The Mechanism of Action of N-acetylcysteine for Reducing the Risk of Infection in Alcoholic Hepatitis
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.
Read the detailed description
Randomised controlled trial, open label.
- Conditions
- Alcoholic Hepatitis, Infection
- Being tested
- N-acetyl cysteine (NAC)
- Medical subject headings
- Hepatitis, Alcoholic, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetyl cysteine (NAC)Drug
Also called NAC
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: N-acetyl cysteine (NAC) |
| prednisolone | No intervention | 40mg prednisolone for 28 days |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in monocyte oxidative burst
Measured: 24 hours
Improvement in ex vivo monocyte oxidative burst
Measured: 5 days
Secondary outcomes (4)
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
Measured: 28 days
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
Measured: 90 days
Death
Measured: 28 days
Death
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2017
- Study start1 Oct 2015
- Primary completion1 Apr 2022 (estimated)
- Study completion1 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alcoholic HepatitisStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized controlled trial
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark Thursz, MD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03069300
- Sponsor's protocol ID
- 14SM2383
- Acronym
- NACAH
- Status last verified
- Nov 2021
- First submitted
- 28 Feb 2017
- Last updated
- 9 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: contact investigators
Publications
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.
PubMed 22070475Vergis 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.
PubMed 26860769
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Mechanism of Action of N-acetylcysteine for Reducing the Risk of Infection in Alcoholic Hepatitis
- ClinicalTrials.gov ID
- NCT03069300
- Acronym / sponsor ID
- NACAH / 14SM2383
- Conditions
- Alcoholic Hepatitis, Infection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 1 Oct 2015 (actual)
- Primary completion
- 1 Apr 2022 (estimated)
- Study completion
- 1 Jun 2025 (estimated)
- First posted
- 3 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| prednisolone+NAC | Experimental | Drug: 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 |
| prednisolone | No intervention | –40mg prednisolone for 28 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Aged 18 years or older
- Clinical alcoholic hepatitis:
Key exclusion criteria (10 listed)
- Alcohol abstinence of >6 weeks prior to randomisation
- Duration of jaundice >3 months
- Other causes of liver disease including:
- Evidence of current malignancy (except non-melanotic skin cancer)
- Previous entry into the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetyl cysteine (NAC)Also: NAC | Drug | prednisolone+NAC |
Primary outcome
Improvement in monocyte oxidative burst
Time frame: 24 hours
Improvement in ex vivo monocyte oxidative burst
Time frame: 5 days
4 secondary outcomes
Proportion of patients infected
Time frame: 28 days
Proportion of patients infected
Time frame: 90 days
Death
Time frame: 28 days
Death
Time frame: 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2021.
- Background: PubMed 22070475Nguyen-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.
- Results publication: PubMed 26860769Vergis 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.
- Individual participant dataSharing planned: Yes. contact investigators
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nikhil Vergis, PhD contact
Mark Thursz, MD contact
Mark Thursz, MD principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing N-acetyl cysteine (NAC) in people with Alcoholic Hepatitis and Infection, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nikhil Vergis, PhD (nvergis@ic.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in monocyte oxidative burst (time frame: 24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03069300, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2021.