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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.
Randomised controlled trial, open label.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| prednisolone | No Intervention | 40mg prednisolone for 28 days |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| N-acetyl cysteine (NAC) | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Improvement in monocyte oxidative burst | 24 hours | |
| Improvement in ex vivo monocyte oxidative burst | 5 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Proportion of patients infected |
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Inclusion Criteria:
Aged 18 years or older
Clinical alcoholic hepatitis:
Exclusion Criteria:
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
Patients with known hypersensitivity or previous reactions to NAC
Pregnant or lactating women
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Nikhil Vergis, PhD | Contact | nvergis@ic.ac.uk | ||
| Mark Thursz, MD | Contact |
| Name | Affiliation | Role |
|---|---|---|
| Mark Thursz, MD | Imperial College London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St Mary's Hospital, Imperial College | Recruiting | London | W2 1NY | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22070475 | Background | 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. | |
| 26860769 |
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contact investigators
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Feb 27, 2024 | |
| Reset | Aug 9, 2024 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Feb 27, 2024 | Aug 9, 2024 |
| ID | Term |
|---|---|
| D006519 | Hepatitis, Alcoholic |
| D007239 | Infections |
| ID | Term |
|---|---|
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D008108 | Liver Diseases, Alcoholic |
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| ID | Term |
|---|---|
| D000111 | Acetylcysteine |
| ID | Term |
|---|---|
| D003545 | Cysteine |
| D000603 | Amino Acids, Sulfur |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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randomized controlled trial
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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 |
| Death | 28 days |
| Death | 90 days |
| 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. |
| D020751 |
| Alcohol-Induced Disorders |
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D000596 |
| Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |