Alcoholic Hepatitis
Conditions
Brief summary
This multicenter, randomized, double blinded, placebo-controlled clinical trial is focused on novel treatments for severe alcoholic hepatitis (AH), a life-threatening stage of alcoholic liver injury that has a short-term mortality rate much higher than that of other liver diseases. The primary objective of the study is to determine the clinical efficacy and safety of Anakinra (plus zinc) compared to the current standard medical treatment consisting of prednisone in participants with clinically severe AH. Key secondary objectives broadly are as follows: (a) to evaluate the use of biomarkers to assess disease severity and treatment response; and (b) to develop novel endpoints to overcome the limitations of current assessment strategies for severe AH.
Interventions
DRUGAnakinra 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.
DRUGPrednisone
Prednisone is indicated for numerous conditions including inflammatory disease. Corticosteroids, such as prednisolone, are considered standard of care in alcoholic liver disease.
DRUGPlacebos
Matching placebo
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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\* 2. MELD 20-35 on day of randomization. 3. 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
1. MELD SCORE \<20 or \> 35 2. Active sepsis (positive blood or ascitic cultures) with Systemic Inflammatory Response Syndrome (SIRS) or hemodynamic compromise requiring intravenous pressors to maintain tissue perfusion 3. Pneumonia as evidenced by radiological exam 4. Multi-organ failure 5. Renal failure defined by GFR \<35 mL/min by CKD-EPI. 6. Clinically active C. diff infection 7. History of imaging of the liver (ultrasound, computerized tomography or magnetic resonance) showing other causes of jaundice 8. 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. 9. History of HIV infection (positive HIV RNA or on treatment for HIV infection) 10. History or presence of cancer (including hepatocellular carcinoma) other than non- melanoma skin cancer 11. History of other significant medical problems such as autoimmune diseases, severe asthma, psoriasis, Inflammatory Bowel Disease (IBD), etc. that might require immunosuppressive treatments 12. Pregnancy or breastfeeding 13. Prior exposure to experimental therapies in last 3 months 14. Prior exposure to systemic corticosteroid (glucocorticoid) or immunosuppressive therapy for more than 4 days within previous 30 days 15. Need for inotropic pressor support to maintain perfusion to critical organs within prior 48 hours before randomization and initiation of experimental treatment 16. Clinically significant pancreatitis- abdominal pain, elevated lipase (\> 3 X ULN) and at least edema of pancreas with fat-stranding on CT scan 17. Total WBC count \> 30,000/mm3 18. Known allergy or intolerance to therapeutic agents to be tested 19. Inability to voluntarily obtain informed consent from participant or guardian 20. Perceived inability to follow study procedures and comply with protocol 21. Platelet count \< 40,000 k/cumm. 22. Positive PCR test for COVID -19 within 7 days prior to the baseline day 0 visit 23. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival at 90 Days | 90 days | The primary analysis will be comparisons of 90-day mortality of Prednisone and Anakinra plus zinc vs Prednisone. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in MELD Score | 7, 30, and 90 days | 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. |
| Number of Participants With AKI (Acute Kidney Injury) | 7, 30, and 90 days | * 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 |
| Development of Multi-organ Failure | 7, 30, and 90 days | Defined as failure ≥2 organs |
| Development of SIRS (Systemic Inflammatory Response Syndrome) | 7, 30, and 90 days | Defined as two or more abnormalities in temperature, increased heart rate, respiration, or white blood cell count with increase in SOFA score ≥2 points |
| Number of Transfers to ICU | 7, 30, and 90 days | Recording the change of hospital word from regular floor to ICU floor as a marker for worsening illness and care escalation |
| Changes in Liver Function | 7, 30, and 90 days | 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. |
| 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. | 180 days | 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) |
| To Measure the Changes in Lille Score | Day 7 | 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. |
| Number of Participants With Progression of Sepsis | 180 days | * 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 |
| Percentage of Participants With Renal Dysfunction | 180 days | Defined by a creatinine \> 2 mg/dl |
| Number of Participants Requiring Transfer to ICU for Care, Intubation for Airway Control, Need for Ventilator Support or RRT. | 180 days | — |
| Indicators of Gut Permeability | 180 days | — |
| Survival | 30 days and 180 days | — |
| Transplant Free Survival Rate | 90 Days | — |
| Number of Participants With Infections | 180 days | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 73 |
| 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 | 74 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up | Lost to Follow-up | 5 | 4 |
| Follow-up | Withdrawal by Subject | 1 | 0 |
| Treatment | Adverse Event | 9 | 5 |
| Treatment | Averse Event and Met Stopping Criteria | 2 | 9 |
| Treatment | Death | 0 | 2 |
| Treatment | Lost to Follow-up | 11 | 3 |
| Treatment | Met Stopping Criteria | 13 | 24 |
| Treatment | Other | 7 | 9 |
| Treatment | Physician Decision | 1 | 0 |
| Treatment | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Prednisone | Total | Anakinra and Zinc |
|---|---|---|---|
| Age, Continuous | 44.9 Years STANDARD_DEVIATION 10.5 | 44.7 Years STANDARD_DEVIATION 9.9 | 44.5 Years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 19 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 126 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 17 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 61 Participants | 121 Participants | 60 Participants |
| Region of Enrollment United States | 73 participants | 147 participants | 74 participants |
| Sex: Female, Male Female | 32 Participants | 59 Participants | 27 Participants |
| Sex: Female, Male Male | 41 Participants | 88 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 73 | 22 / 74 |
| other Total, other adverse events | 45 / 73 | 51 / 74 |
| serious Total, serious adverse events | 41 / 73 | 49 / 74 |
Outcome results
Primary
Survival at 90 Days
The primary analysis will be comparisons of 90-day mortality of Prednisone and Anakinra plus zinc vs Prednisone.
Time frame: 90 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisone | Survival at 90 Days | 90 percentage of participants |
| Anakinra and Zinc | Survival at 90 Days | 70 percentage of participants |
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.
Time frame: 7, 30, and 90 days
Population: Due to lab issues and participant follow-up at certain sites, numbers analyzed differ from lab test to timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone | Changes in Liver Function | Day 0 | 10.3 score on a scale | Standard Deviation 1.7 |
| Prednisone | Changes in Liver Function | Day 7 | 9.4 score on a scale | Standard Deviation 1.5 |
| Prednisone | Changes in Liver Function | Day 30 | 8.5 score on a scale | Standard Deviation 2 |
| Prednisone | Changes in Liver Function | Day 90 | 7.2 score on a scale | Standard Deviation 2 |
| Anakinra and Zinc | Changes in Liver Function | Day 90 | 8.0 score on a scale | Standard Deviation 1.8 |
| Anakinra and Zinc | Changes in Liver Function | Day 0 | 10.1 score on a scale | Standard Deviation 1.4 |
| Anakinra and Zinc | Changes in Liver Function | Day 30 | 9.2 score on a scale | Standard Deviation 2 |
| Anakinra and Zinc | Changes in Liver Function | Day 7 | 9.7 score on a scale | Standard Deviation 1.6 |
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.
Time frame: 7, 30, and 90 days
Population: Participant numbers may vary from participant workflow module due to the data that was able to be collected at sites and timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone | Changes in MELD Score | Day 7 | -2.8 scores on a scale | Standard Deviation 2.9 |
| Prednisone | Changes in MELD Score | Day 30 | -6.9 scores on a scale | Standard Deviation 5.3 |
| Prednisone | Changes in MELD Score | Day 90 | -10.3 scores on a scale | Standard Deviation 6.1 |
| Anakinra and Zinc | Changes in MELD Score | Day 7 | 0.2 scores on a scale | Standard Deviation 4.6 |
| Anakinra and Zinc | Changes in MELD Score | Day 30 | -1.6 scores on a scale | Standard Deviation 8.3 |
| Anakinra and Zinc | Changes in MELD Score | Day 90 | -8.1 scores on a scale | Standard Deviation 7.1 |
Secondary
Development of Multi-organ Failure
Defined as failure ≥2 organs
Time frame: 7, 30, and 90 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prednisone | Development of Multi-organ Failure | Day 7 | 3 Number of Subjects |
| Prednisone | Development of Multi-organ Failure | Day 30 | 1 Number of Subjects |
| Prednisone | Development of Multi-organ Failure | Day 90 | 1 Number of Subjects |
| Anakinra and Zinc | Development of Multi-organ Failure | Day 7 | 2 Number of Subjects |
| Anakinra and Zinc | Development of Multi-organ Failure | Day 30 | 4 Number of Subjects |
| Anakinra and Zinc | Development of Multi-organ Failure | Day 90 | 1 Number of Subjects |
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
Time frame: 7, 30, and 90 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prednisone | Development of SIRS (Systemic Inflammatory Response Syndrome) | Day 7 | 0 Events |
| Prednisone | Development of SIRS (Systemic Inflammatory Response Syndrome) | Day 30 | 2 Events |
| Prednisone | Development of SIRS (Systemic Inflammatory Response Syndrome) | Day 90 | 1 Events |
| Anakinra and Zinc | Development of SIRS (Systemic Inflammatory Response Syndrome) | Day 7 | 2 Events |
| Anakinra and Zinc | Development of SIRS (Systemic Inflammatory Response Syndrome) | Day 30 | 0 Events |
| Anakinra and Zinc | Development of SIRS (Systemic Inflammatory Response Syndrome) | Day 90 | 0 Events |
Secondary
Indicators of Gut Permeability
Time frame: 180 days
Population: Zero participants analyzed, data were not collected
Secondary
Number of Participants Requiring Transfer to ICU for Care, Intubation for Airway Control, Need for Ventilator Support or RRT.
Time frame: 180 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisone | Number of Participants Requiring Transfer to ICU for Care, Intubation for Airway Control, Need for Ventilator Support or RRT. | 6 Participant counts |
| Anakinra and Zinc | Number of Participants Requiring Transfer to ICU for Care, Intubation for Airway Control, Need for Ventilator Support or RRT. | 15 Participant counts |
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
Time frame: 7, 30, and 90 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prednisone | Number of Participants With AKI (Acute Kidney Injury) | Day 7 | 4 Participants |
| Prednisone | Number of Participants With AKI (Acute Kidney Injury) | Day 30 | 6 Participants |
| Prednisone | Number of Participants With AKI (Acute Kidney Injury) | Day 90 | 5 Participants |
| Anakinra and Zinc | Number of Participants With AKI (Acute Kidney Injury) | Day 7 | 17 Participants |
| Anakinra and Zinc | Number of Participants With AKI (Acute Kidney Injury) | Day 30 | 20 Participants |
| Anakinra and Zinc | Number of Participants With AKI (Acute Kidney Injury) | Day 90 | 5 Participants |
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)
Time frame: 180 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prednisone | 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. | Increase in SOFA > 2 points | 3 Participants |
| Prednisone | 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. | Need for hemodynamic support | 9 Participants |
| Prednisone | 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. | Renal replacement therapy | 7 Participants |
| Anakinra and Zinc | 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. | Increase in SOFA > 2 points | 3 Participants |
| Anakinra and Zinc | 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. | Need for hemodynamic support | 11 Participants |
| Anakinra and Zinc | 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. | Renal replacement therapy | 10 Participants |
Secondary
Number of Participants With Infections
Time frame: 180 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisone | Number of Participants With Infections | 20 participants |
| Anakinra and Zinc | Number of Participants With Infections | 23 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
Time frame: 180 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prednisone | Number of Participants With Progression of Sepsis | Sepsis | 3 Participants |
| Prednisone | Number of Participants With Progression of Sepsis | Sepsis shock | 2 Participants |
| Anakinra and Zinc | Number of Participants With Progression of Sepsis | Sepsis | 0 Participants |
| Anakinra and Zinc | Number of Participants With Progression of Sepsis | Sepsis shock | 5 Participants |
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
Time frame: 7, 30, and 90 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prednisone | Number of Transfers to ICU | Day 7 | 2 Transfers |
| Prednisone | Number of Transfers to ICU | Day 30 | 2 Transfers |
| Prednisone | Number of Transfers to ICU | Day 90 | 2 Transfers |
| Anakinra and Zinc | Number of Transfers to ICU | Day 7 | 5 Transfers |
| Anakinra and Zinc | Number of Transfers to ICU | Day 30 | 9 Transfers |
| Anakinra and Zinc | Number of Transfers to ICU | Day 90 | 0 Transfers |
Secondary
Percentage of Participants With Renal Dysfunction
Defined by a creatinine \> 2 mg/dl
Time frame: 180 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisone | Percentage of Participants With Renal Dysfunction | 21.9 Percentage of Participants |
| Anakinra and Zinc | Percentage of Participants With Renal Dysfunction | 47.3 Percentage of Participants |
Secondary
Survival
Time frame: 30 days and 180 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prednisone | Survival | Day 30 | 97 Percentage of Participants |
| Prednisone | Survival | Day 180 | 81 Percentage of Participants |
| Anakinra and Zinc | Survival | Day 30 | 85 Percentage of Participants |
| Anakinra and Zinc | Survival | Day 180 | 68 Percentage of Participants |
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.
Time frame: Day 7
Population: Participant numbers may vary from participant workflow module due to the data that was able to be collected at sites and timepoints.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisone | To Measure the Changes in Lille Score | 67.8 percentage of participants |
| Anakinra and Zinc | To Measure the Changes in Lille Score | 65.6 percentage of participants |
Secondary
Transplant Free Survival Rate
Time frame: 90 Days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisone | Transplant Free Survival Rate | 88 Percentage of Participants |
| Anakinra and Zinc | Transplant Free Survival Rate | 64 Percentage of Participants |