Trial of Anakinra (Plus Zinc) or Prednisone in Patients W... | NCT04072822

Name	Class
National Institute on Alcohol Abuse and Alcoholism (NIAAA)	NIH

Label	Type	Description	Intervention Names
Prednisone	Active Comparator	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90).	Drug: Prednisone Drug: Placebos
Anakinra and Zinc	Active Comparator	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30).	Drug: Anakinra and Zinc Drug: Placebos

Name	Type	Description	Arm Group Labels	Other Names
Anakinra and Zinc	Drug	Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease.

Measure	Description	Time Frame
Survival at 90 Days	The primary analysis will be comparisons of 90-day mortality of Prednisone and Anakinra plus zinc vs Prednisone.	90 days

Measure	Description	Time Frame
To Measure the Changes in Lille Score	Change in Lille score is represented as the percentage of participants who achieved a Lille score < 0.45 on day 7. The Lille score will be calculated using the following website: https://www.mdcalc.com/lille-model-alcoholic-hepatitis Lille score = (exp(-R))/(1 + exp(-R)) where the variables are as follows: R = 3.19 - 0.101(age, years) + 0.147(albumin day 0, g/L) + 0.0165* (evolution in bilirubin level, µmol/L) - 0.206(renal insufficiency) - 0.0065(bilirubin day 0, µmol/L) - 0.0096*(prothrombin time, sec) Renal insufficiency = 1 (if creatinine >1.3 mg/dL (115 µmol/L)) or 0 (if ≤1.3 mg/dL (115 µmol/L)) The Lille score was developed to provide early recognition of patients with severe alcoholic hepatitis not responding to corticosteroids. Lower scores indicate more improvement in response to corticosteroids. A Lille score > 0.45 predicts worse 6-month survival. A Lille score < 0.45 predicts better 6-month survival.

Eligibility Module

Eligibility Criteria

Inclusion Criteria

AH, as defined by the NIAAA pan-consortia for AH:
1. Onset of jaundice (defined as serum total bilirubin >3 mg/dL) within the prior 8 weeks to screening visit
2. Regular consumption of alcohol with an intake of > 40 gm daily or >280gm weekly on average for women and > 60 gm daily or >420gm weekly on average for men for 6 months or more, with less than 8 weeks of abstinence before onset of jaundice
3. AST > 50 IU/l
4. AST:ALT > 1.5 and both values < 400 IU/l
5. and/or histological evidence of AH*
MELD 20-35 on day of randomization.
Ages >21
- In patients with possible AH or AH with confounding factors such as possible ischemic hepatitis, possible DILI, uncertain history of alcohol use (e.g., patient denies excessive alcohol use), and atypical/abnormal laboratory tests (e.g., AST < 50 IU/L or > 400 IU/L, AST/ALT ratio < 1.5), antinuclear antibody > 1:160 or SMA > 1:80, a standard of care liver biopsy may be performed during current hospital admission to confirm AH and exclude competing etiologies

Exclusion Criteria

MELD SCORE <20 or > 35
Active sepsis (positive blood or ascitic cultures) with Systemic Inflammatory Response Syndrome (SIRS) or hemodynamic compromise requiring intravenous pressors to maintain tissue perfusion
Pneumonia as evidenced by radiological exam
Multi-organ failure
Renal failure defined by GFR <35 mL/min by CKD-EPI.
Clinically active C. diff infection
History of imaging of the liver (ultrasound, computerized tomography or magnetic resonance) showing other causes of jaundice
History of other liver diseases including hepatitis B (positive HBsAg or HBV DNA), hepatitis C (positive HCV RNA), autoimmune hepatitis, Wilson disease, genetic \hemochromatosis, alpha1-antitrypsin deficiency or strong suspicion of Drug Induced Liver Injury (DILI). Previously treated hepatitis C that was cured (sustained virological response with negative RNA ≥24 weeks following treatment) is not an exclusion.
History of HIV infection (positive HIV RNA or on treatment for HIV infection)
History or presence of cancer (including hepatocellular carcinoma) other than non- melanoma skin cancer
History of other significant medical problems such as autoimmune diseases, severe asthma, psoriasis, Inflammatory Bowel Disease (IBD), etc. that might require immunosuppressive treatments
Pregnancy or breastfeeding
Prior exposure to experimental therapies in last 3 months
Prior exposure to systemic corticosteroid (glucocorticoid) or immunosuppressive therapy for more than 4 days within previous 30 days
Need for inotropic pressor support to maintain perfusion to critical organs within prior 48 hours before randomization and initiation of experimental treatment
Clinically significant pancreatitis- abdominal pain, elevated lipase (> 3 X ULN) and at least edema of pancreas with fat-stranding on CT scan
Total WBC count > 30,000/mm3
Known allergy or intolerance to therapeutic agents to be tested
Inability to voluntarily obtain informed consent from participant or guardian
Perceived inability to follow study procedures and comply with protocol
Platelet count < 40,000 k/cumm.
Positive PCR test for COVID -19 within 7 days prior to the baseline day 0 visit
Active gastrointestinal bleeding defined as hematemesis or melena with a decrease in hemoglobin more than 2 g/dl in 24 hrs. Due to gastrointestinal bleeding, or with a decrease in mean arterial BP to < 65 mmHg.
- Positive test is exclusionary only during screening period. If a patient tests positive any time after baseline randomization, a positive PCR test for COVID-19 will be considered as a SAE.

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic		Phoenix	Arizona	85054	United States
Mayo Clinic

PubMed Identifier	Type	Citation	Retractions
38342441	Derived	Gawrieh S, Dasarathy S, Tu W, Kamath PS, Chalasani NP, McClain CJ, Bataller R, Szabo G, Tang Q, Radaeva S, Barton B, Nagy LE, Shah VH, Sanyal AJ, Mitchell MC; AlcHepNet Investigators. Randomized trial of anakinra plus zinc vs. prednisone for severe alcohol-associated hepatitis. J Hepatol. 2024 May;80(5):684-693. doi: 10.1016/j.jhep.2024.01.031. Epub 2024 Feb 10.
38215876

Label	URL
AlcHepNet Website	View source

ID	Title	Description
FG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jan 31, 2022

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Survival at 90 Days

The primary analysis will be comparisons of 90-day mortality of Prednisone and Anakinra plus zinc vs Prednisone.

Posted

Number

percentage of participants

90 days

ID	Title	Description
OG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
OG001	Anakinra and Zinc	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30). Anakinra and Zinc: Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease.

Units	Counts
Participants	OG00073 OG00174

Title

Denominators

Categories

Title	Measurements
	OG00090 OG00170

Secondary

To Measure the Changes in Lille Score

Change in Lille score is represented as the percentage of participants who achieved a Lille score < 0.45 on day 7.

The Lille score will be calculated using the following website: https://www.mdcalc.com/lille-model-alcoholic-hepatitis Lille score = (exp(-R))/(1 + exp(-R)) where the variables are as follows: R = 3.19 - 0.101*(age, years) + 0.147*(albumin day 0, g/L) + 0.0165* (evolution in bilirubin level, µmol/L) - 0.206*(renal insufficiency) - 0.0065*(bilirubin day 0, µmol/L) - 0.0096*(prothrombin time, sec) Renal insufficiency = 1 (if creatinine >1.3 mg/dL (115 µmol/L)) or 0 (if ≤1.3 mg/dL (115 µmol/L)) The Lille score was developed to provide early recognition of patients with severe alcoholic hepatitis not responding to corticosteroids. Lower scores indicate more improvement in response to corticosteroids. A Lille score > 0.45 predicts worse 6-month survival. A Lille score < 0.45 predicts better 6-month survival.

Participant numbers may vary from participant workflow module due to the data that was able to be collected at sites and timepoints.

Posted

Number

percentage of participants

Day 7

ID	Title	Description
OG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
OG001

Secondary

Changes in MELD Score

The Model for End-Stage Liver Disease (MELD) is a numerical scale, ranging from 6 (less ill) to 40 (gravely ill), used for liver transplant candidates age 12 and older. It gives each person a 'score' (number) based on how urgently he or she needs a liver transplant within the next three months.

Participant numbers may vary from participant workflow module due to the data that was able to be collected at sites and timepoints.

Posted

Mean

Standard Deviation

scores on a scale

7, 30, and 90 days

ID	Title	Description
OG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
OG001	Anakinra and Zinc	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30). Anakinra and Zinc: Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease.

Secondary

Number of Participants With AKI (Acute Kidney Injury)

Increase in creatinine of 50% above baseline over a period of 7 days
Increase in creatinine of 0.3 mg/dl within a period of 48 hrs
Onset of renal failure requiring dialysis

Posted

Number

Participants

7, 30, and 90 days

ID	Title	Description
OG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
OG001	Anakinra and Zinc	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30). Anakinra and Zinc: Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease.

Secondary

Development of Multi-organ Failure

Defined as failure ≥2 organs

Posted

Number

Number of Subjects

7, 30, and 90 days

ID	Title	Description
OG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
OG001	Anakinra and Zinc	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30). Anakinra and Zinc: Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease.

Units	Counts
Participants

Secondary

Development of SIRS (Systemic Inflammatory Response Syndrome)

Defined as two or more abnormalities in temperature, increased heart rate, respiration, or white blood cell count with increase in SOFA score ≥2 points

Posted

Number

Events

7, 30, and 90 days

ID	Title	Description
OG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
OG001	Anakinra and Zinc	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30). Anakinra and Zinc: Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease.

Secondary

Number of Transfers to ICU

Recording the change of hospital word from regular floor to ICU floor as a marker for worsening illness and care escalation

Posted

Number

Transfers

7, 30, and 90 days

ID	Title	Description
OG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
OG001	Anakinra and Zinc	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30). Anakinra and Zinc: Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease.

Units	Counts

Secondary

Changes in Liver Function

Changes in liver function were evaluated by changes in the Child Pugh Score at days 7, 30, and 90. The Child Pugh Score is a scoring system used to assess the severity of chronic liver disease. Scores range from 5 to 15, with higher scores indicating more severe disease. Points are assigned as follows:

Hepatic encephalopathy: None = 1 point, Grade 1 and 2 = 2 points, Grade 3 and 4 = 3 points Ascites: None = 1 point, mild = 2 points, moderate to severe = 3 points Total Bilirubin: under 2 mg/dl = 1 point, 2 to 3 mg/dl = 2 points, over 3 mg/dl = 3 points Albumin: greater than 3.5g/dl = 1 point, 2.8 to 3.5g/dl = 2 points, less than 2.8g/dl = 3 points International normalised ratio (INR): under 1.7 = 1 point, 1.7 to 2.3 = 2 points, above 2.3 = 3 points

Assigned points for each category are summed to calculate the Child Pugh Score.

Due to lab issues and participant follow-up at certain sites, numbers analyzed differ from lab test to timepoint

Posted

Mean

Standard Deviation

score on a scale

7, 30, and 90 days

ID	Title	Description
OG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
OG001	Anakinra and Zinc

Secondary

Number of Participants With Changes in Sequential Organ Failure Assessment (SOFA) Scores and Proportions Requiring Hemodynamic Support for MAP < 65 mm Hg and Lactate > 2 mmol/l, Renal Replacement Therapy or Mechanical Ventilation.

The SOFA score will be calculated at the following website https://www.mdcalc.com/sequential-organ-failure-assessment-sofa-score

Scores can be from 0 - >14 (favorable to less favorable)

Posted

Number

Participants

180 days

ID	Title	Description
OG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
OG001	Anakinra and Zinc	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30). Anakinra and Zinc: Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease.

Secondary

Number of Participants With Infections

Posted

Number

participants

180 days

ID	Title	Description
OG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
OG001	Anakinra and Zinc	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30). Anakinra and Zinc: Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease.

Units	Counts
Participants

Secondary

Number of Participants With Progression of Sepsis

Life-threatening organ dysfunction caused by a dysregulated host response to infection
An increase in SOFA score of 2 points of more
Note: most participants with severe AH have 4 points based on bilirubin only

Posted

Number

Participants

180 days

ID	Title	Description
OG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
OG001	Anakinra and Zinc	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30). Anakinra and Zinc: Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease.

Secondary

Percentage of Participants With Renal Dysfunction

Defined by a creatinine > 2 mg/dl

Posted

Number

Percentage of Participants

180 days

ID	Title	Description
OG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
OG001	Anakinra and Zinc	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30). Anakinra and Zinc: Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease.

Units	Counts
Participants

Secondary

Number of Participants Requiring Transfer to ICU for Care, Intubation for Airway Control, Need for Ventilator Support or RRT.

Posted

Number

Participant counts

180 days

ID	Title	Description
OG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
OG001	Anakinra and Zinc	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30). Anakinra and Zinc: Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease.

Units	Counts
Participants

Secondary

Indicators of Gut Permeability

Zero participants analyzed, data were not collected

Posted

180 days

ID	Title	Description
OG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
OG001	Anakinra and Zinc	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30). Anakinra and Zinc: Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease.

Units	Counts
Participants

Secondary

Survival

Posted

Number

Percentage of Participants

30 days and 180 days

ID	Title	Description
OG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
OG001	Anakinra and Zinc	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30). Anakinra and Zinc: Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease.

Units	Counts
Participants

Secondary

Transplant Free Survival Rate

Posted

Number

Percentage of Participants

90 Days

ID	Title	Description
OG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
OG001	Anakinra and Zinc	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30). Anakinra and Zinc: Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
ARDS	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Abdominal Distension	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0004 events4 affected73 at risk EG0017 events4 affected74 at risk
Abdominal pain generalized	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Abdominal wall hematoma	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Acute anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0012 events2 affected74 at risk
Acute cholecystitis	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Acute Kidney Injury	Renal and urinary disorders	Systematic Assessment	EG00015 events13 affected73 at risk EG00136 events30 affected74 at risk
Acute post hemorrhagic anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0004 events3 affected73 at risk EG0013 events3 affected74 at risk
Alcohol intoxication	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Alcoholic hepatitis	Hepatobiliary disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Alcoholic withdrawal symptoms	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Anasarca	Hepatobiliary disorders	Systematic Assessment	EG0005 events4 affected73 at risk EG0010 events0 affected74 at risk
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0011 events1 affected74 at risk
Ascites	Hepatobiliary disorders	Systematic Assessment	EG0002 events2 affected73 at risk EG0015 events5 affected74 at risk
Ataxia	Nervous system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Bacteremia	Infections and infestations	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Bleeding tendencies	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Blood in stool	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
C.difficile colitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
COVID-19 pneumonia	Infections and infestations	Systematic Assessment	EG0003 events3 affected73 at risk EG0012 events2 affected74 at risk
Cardiac arrest	Cardiac disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Cardiogenic pulmonary edema	Cardiac disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Cellulitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected73 at risk EG0012 events2 affected74 at risk
Central line infection	Infections and infestations	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Chronic pancreatitis	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Clostridium difficile colitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Confusion	Nervous system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Death	General disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Deep vein thrombosis leg	Vascular disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Depression	Psychiatric disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Detoxification	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Empyema	Infections and infestations	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Encephalopathy	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Encephalopathy hepatic	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Encephalopathy toxic acute	Nervous system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Epistaxis	General disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Esophageal varices hemorrhage	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Evacuation of subdural hematoma	Nervous system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Fall	General disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0011 events1 affected74 at risk
Fever	General disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Fluid overload	Cardiac disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
GI bleed	Gastrointestinal disorders	Systematic Assessment	EG0004 events3 affected73 at risk EG0016 events5 affected74 at risk
Gastric ulcer hemorrhagic	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Generalized edema	Cardiac disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Hallucination	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Hematemesis	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Hematochezia	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0011 events1 affected74 at risk
Hematoma muscle	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Hemoperitoneum	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Hemoptysis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Hemorrhage	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Hepatic encephalopathy	Hepatobiliary disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0015 events5 affected74 at risk
Hospice care	General disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Hyperglycemia	Endocrine disorders	Systematic Assessment	EG0002 events2 affected73 at risk EG0010 events0 affected74 at risk
Hypoglycemia	Endocrine disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Hypokalemia	Renal and urinary disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0013 events3 affected74 at risk
Hyponatremia	Renal and urinary disorders	Systematic Assessment	EG0005 events3 affected73 at risk EG0013 events3 affected74 at risk
Hypotension	Cardiac disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0011 events1 affected74 at risk
Hypotonic dehydration	Vascular disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Hypoxic respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0003 events2 affected73 at risk EG0011 events1 affected74 at risk
Ileus of colon	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Increased shortness of breath	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0012 events1 affected74 at risk
Internal bleeding	Vascular disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Intra-abdominal hemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Intracranial hemorrhage	Nervous system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Lactic acidosis	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Leg pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Leukocytosis	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Liver function test increased	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Liver transplant	Surgical and medical procedures	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Macrocytic anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Metabolic acidosis	Renal and urinary disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Multi-organ failure	General disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Nausea and vomiting symptoms	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected73 at risk EG0010 events0 affected74 at risk
Neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Pelvic abscess	Infections and infestations	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Pericarditis	Cardiac disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Perineal abscess	Pregnancy, puerperium and perinatal conditions	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Pneumonia	Infections and infestations	Systematic Assessment	EG0004 events3 affected73 at risk EG0013 events3 affected74 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
RUQ pain	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Rectal bleeding	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Refractory shock	Cardiac disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0012 events2 affected74 at risk
Retroperitoneal hemorrhage	Vascular disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
SIRS	Infections and infestations	Systematic Assessment	EG0003 events2 affected73 at risk EG0011 events1 affected74 at risk
STEMI	Cardiac disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Seizure	Nervous system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Sepsis	Infections and infestations	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Septic arthritis	Infections and infestations	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Septic shock	Infections and infestations	Systematic Assessment	EG0002 events2 affected73 at risk EG0015 events5 affected74 at risk
Serum creatinine increased	Renal and urinary disorders	Systematic Assessment	EG0002 events2 affected73 at risk EG0010 events0 affected74 at risk
Shock	Cardiac disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0013 events3 affected74 at risk
Shock circulatory	Cardiac disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Shortness of breath	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Spontaneous bacterial peritonitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected73 at risk EG0012 events2 affected74 at risk
Subdural hematoma	Nervous system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0012 events1 affected74 at risk
Substance-induced mood disorder	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Thrombocytopenia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0002 events2 affected73 at risk EG0012 events2 affected74 at risk
Varicella zoster virus infection	Infections and infestations	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Abdominal Distension	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0012 events1 affected74 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected73 at risk EG0014 events4 affected74 at risk
Abnormal chest sounds	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0012 events2 affected74 at risk
Abnormal uterine bleeding	Reproductive system and breast disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Accidental overdose (therapeutic agent)	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Acute confusional state	Nervous system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Acute kidney injury	Renal and urinary disorders	Systematic Assessment	EG0003 events3 affected73 at risk EG0019 events8 affected74 at risk
Agitation	Nervous system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Alanine aminotransferase increased	Hepatobiliary disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Alcohol intoxication acute	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Alcoholic cirrhosis of liver	Hepatobiliary disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Allergy	Immune system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Anasarca	Hepatobiliary disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0002 events2 affected73 at risk EG0010 events0 affected74 at risk
Ankle edema	Cardiac disorders	Systematic Assessment	EG0002 events2 affected73 at risk EG0010 events0 affected74 at risk
Ankle swelling	Cardiac disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0011 events1 affected74 at risk
Anxiety	Psychiatric disorders	Systematic Assessment	EG0002 events2 affected73 at risk EG0010 events0 affected74 at risk
Aphasia	Nervous system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Ascites	Hepatobiliary disorders	Systematic Assessment	EG0005 events5 affected73 at risk EG00119 events6 affected74 at risk
Ascites grade 2	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0012 events2 affected74 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0012 events2 affected74 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0012 events2 affected74 at risk
Bacteremia	Infections and infestations	Systematic Assessment	EG0001 events1 affected73 at risk EG0011 events1 affected74 at risk
Bleeding	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Blurred vision	Eye disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Breast tenderness	Reproductive system and breast disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Breath sounds	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
COVID-19 pneumonia	Infections and infestations	Systematic Assessment	EG0002 events2 affected73 at risk EG0011 events1 affected74 at risk
Cellulitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Central line infection	Infections and infestations	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Chest pain	Cardiac disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Clostridium difficile colitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Coagulopathy	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0011 events1 affected74 at risk
Confusion	Nervous system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0011 events1 affected74 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected73 at risk EG0011 events1 affected74 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 events2 affected73 at risk EG0013 events3 affected74 at risk
Cough nonproductive	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Crackles lung	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Dehydration	Vascular disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Depression	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected73 at risk EG0013 events3 affected74 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Dry mouth	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Dry skin	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Dysgeusia	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Dyspepsia	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Dysuria	Renal and urinary disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Ecchymosis injection site	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Edema	Cardiac disorders	Systematic Assessment	EG0002 events2 affected73 at risk EG0011 events1 affected74 at risk
Edema dependent	Cardiac disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Edema limbs	Cardiac disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Edema lower limb	Cardiac disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Edema of legs	Cardiac disorders	Systematic Assessment	EG0004 events2 affected73 at risk EG0013 events3 affected74 at risk
Edema of lower extremities	Cardiac disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Edema pulmonary	Cardiac disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Elevated liver enzyme levels	Hepatobiliary disorders	Systematic Assessment	EG0003 events3 affected73 at risk EG0010 events0 affected74 at risk
Encephalopathy	Hepatobiliary disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Encephalopathy acute	Hepatobiliary disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0011 events1 affected74 at risk
Encephalopathy hepatic	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Epigastric pain	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Erythematous rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Esophageal varices without mention of bleeding	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Fall	General disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0012 events2 affected74 at risk
Fatigue	General disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0012 events2 affected74 at risk
Fever	General disorders	Systematic Assessment	EG0002 events2 affected73 at risk EG0012 events2 affected74 at risk
Foot pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0002 events1 affected73 at risk EG0010 events0 affected74 at risk
Gas pain	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0011 events1 affected74 at risk
Gastrocnemius equinus	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Glucose abnormal	Endocrine disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Gout	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Hallucinations	Nervous system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0011 events1 affected74 at risk
Headache	Nervous system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Heartburn	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Hematemesis	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Hematochezia	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Hematoma	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Hemorrhoids	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Hepatic encephalopathy	Nervous system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0014 events3 affected74 at risk
Hepatosplenomegaly	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0012 events2 affected74 at risk
Hydronephrosis	Renal and urinary disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Hypercoagulation	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Hyperglycemia	Endocrine disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0013 events2 affected74 at risk
Hyperglycemia drug-induced	Endocrine disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Hyperkalemia	Renal and urinary disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Hypoalbuminemia	Hepatobiliary disorders	Systematic Assessment	EG0002 events2 affected73 at risk EG0010 events0 affected74 at risk
Hypokalemia	Renal and urinary disorders	Systematic Assessment	EG0008 events7 affected73 at risk EG0017 events7 affected74 at risk
Hypomagnesaemia	Renal and urinary disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0012 events2 affected74 at risk
Hyponatremia	Renal and urinary disorders	Systematic Assessment	EG0003 events2 affected73 at risk EG0014 events4 affected74 at risk
Hypophosphatemia	Renal and urinary disorders	Systematic Assessment	EG0002 events2 affected73 at risk EG0010 events0 affected74 at risk
Hypotension	Cardiac disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
INR increased	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Ileus	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Indigestion	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Infusion reaction	Immune system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Injection site reaction	Immune system disorders	Systematic Assessment	EG0003 events3 affected73 at risk EG0012 events2 affected74 at risk
Insomnia	Nervous system disorders	Systematic Assessment	EG0009 events9 affected73 at risk EG0011 events1 affected74 at risk
Itching	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0004 events4 affected73 at risk EG0011 events1 affected74 at risk
Klebsiella pneumoniae pneumonia	Infections and infestations	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Left upper quadrant pain	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Leukocytosis	Blood and lymphatic system disorders	Systematic Assessment	EG0009 events8 affected73 at risk EG0014 events4 affected74 at risk
Libido decreased	Reproductive system and breast disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Liver scan NOS abnormal	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Loose stools	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Low back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0012 events2 affected74 at risk
Lower leg edema	Cardiac disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Macrocytic anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Malaise	General disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Mental status changes	Nervous system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Muscle injury	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Muscular back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Myalgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0007 events7 affected73 at risk EG0017 events7 affected74 at risk
Nausea and vomiting symptoms	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0013 events3 affected74 at risk
Neuropathy	Nervous system disorders	Systematic Assessment	EG0003 events3 affected73 at risk EG0010 events0 affected74 at risk
Nicotine craving	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Night sweats	General disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0011 events1 affected74 at risk
Nosebleed	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Paracentesis	Gastrointestinal disorders	Systematic Assessment	EG0002 events1 affected73 at risk EG0014 events3 affected74 at risk
Paracentesis abdominis	Surgical and medical procedures	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Pedal edema	Cardiac disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Peripheral edema	Cardiac disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Pneumonia	Infections and infestations	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Portal hypertension	Hepatobiliary disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Pruritic rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Pruritus	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0012 events2 affected74 at risk
Rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Rash (nonspecific)	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Rash NOS	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Restless legs	Nervous system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Retroperitoneal lymphadenopathy	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Rosacea	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Serum creatinine increased	Renal and urinary disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0012 events2 affected74 at risk
Shallow breathing	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Shortness of breath	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0011 events1 affected74 at risk
Sore throat	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Spider angioma	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0002 events2 affected73 at risk EG0011 events1 affected74 at risk
Splenomegaly	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Spontaneous bacterial peritonitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Tachycardia	Cardiac disorders	Systematic Assessment	EG0003 events3 affected73 at risk EG0011 events1 affected74 at risk
Temperature elevation	General disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Thrombocytopenia	Blood and lymphatic system disorders	Systematic Assessment	EG0003 events3 affected73 at risk EG0012 events2 affected74 at risk
Thrombocytosis	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Thrombophlebitis arm superficial	Vascular disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Tibia fracture	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Transjugular intrahepatic portosystemic shunt	Surgical and medical procedures	Systematic Assessment	EG0001 events1 affected73 at risk EG0011 events1 affected74 at risk
Umbilical hernia	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
Unsteady gait	Nervous system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Urgency urination	Renal and urinary disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Urinary incontinence	Renal and urinary disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected73 at risk EG0013 events3 affected74 at risk
Vasopressin decreased urine output	Renal and urinary disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0012 events2 affected74 at risk
WBC decreased	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected74 at risk
WBC increased	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk
Weakness	General disorders	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected74 at risk

ID	Term
D006505	Hepatitis
D008107	Liver Diseases
D004066	Digestive System Diseases
D008108	Liver Diseases, Alcoholic
D020751	Alcohol-Induced Disorders
D019973	Alcohol-Related Disorders
D019966	Substance-Related Disorders
D064419	Chemically-Induced Disorders

ID	Term
D016207	Cytokines
D036341	Intercellular Signaling Peptides and Proteins
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D011506	Proteins
D001685	Biological Factors
D019216	Metals, Heavy
D004602	Elements
D007287	Inorganic Chemicals
D028561	Transition Elements
D008670	Metals
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds

ID	Title	Description
BG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease. Placebos: Matching placebo
BG001	Anakinra and Zinc	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30). Anakinra and Zinc: Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease. Placebos: Matching placebo
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Prednisone	Standard of care plus prednisone 40 mg orally once daily on Days 1-30 and matching placebos for Anakinra (1 syringe s.c. once daily on Days 1-14), and zinc (matched pill once daily on Days 1-90). Prednisone: Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.	12	73	41	73	45	73
EG001	Anakinra and Zinc	Standard of care plus Anakinra (100 mg s.c.) once daily on Days 1-14 zinc sulfate 220 mg once daily on Days 1-90, and placebo for prednisone (matched pill once daily on Days 1-30). Anakinra and Zinc: Anakinra is indicated for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis. It has been previously studied in AH. Zinc is a nutritional supplement. Zinc supplementation reverses the clinical signs of zinc deficiency in participants with alcoholic liver disease.	22	74	49	74	51	74

ID	Term
D053590	Interleukin 1 Receptor Antagonist Protein
D015032	Zinc
D011241	Prednisone