Phase 2
N=147
Trial of Anakinra (Plus Zinc) or Prednisone in Patients With Severe Alcoholic Hepatitis
Alcoholic Hepatitis
Bottom Line
View on ClinicalTrials.gov: NCT04072822 ↗Enrolled (actual)
147
Serious AEs
61.2%
Results posted
Jul 2023
Primary outcome: Primary: Survival at 90 Days — 90; 70 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Anakinra and Zinc (Drug); Prednisone (Drug); Placebos (Drug)
- Age
- Adult, Older Adult · 21+ yrs
- Sex
- All
- Sponsor
- Indiana University
- Primary completion
- May 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Survival at 90 Days |
90; 70 | — |
| SECONDARY To Measure the Changes in Lille Score |
67.8; 65.6 | — |
| SECONDARY Changes in MELD Score |
-2.8; 0.2; -6.9; -1.6; -10.3; -8.1 | — |
| SECONDARY Number of Participants With AKI (Acute Kidney Injury) |
4; 17; 6; 20; 5; 5 | — |
| SECONDARY Development of Multi-organ Failure |
3; 2; 1; 4; 1; 1 | — |
| SECONDARY Development of SIRS (Systemic Inflammatory Response Syndrome) |
0; 2; 2; 0; 1; 0 | — |
| SECONDARY Number of Transfers to ICU |
2; 5; 2; 9; 2; 0 | — |
| SECONDARY Changes in Liver Function |
10.3; 10.1; 9.4; 9.7; 8.5; 9.2 | — |
| 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. |
3; 3; 9; 11; 7; 10 | — |
| SECONDARY Number of Participants With Infections |
20; 23 | — |
| SECONDARY Number of Participants With Progression of Sepsis |
3; 0; 2; 5 | — |
| SECONDARY Percentage of Participants With Renal Dysfunction |
21.9; 47.3 | — |
| SECONDARY Number of Participants Requiring Transfer to ICU for Care, Intubation for Airway Control, Need for Ventilator Support or RRT. |
6; 15 | — |
| SECONDARY Indicators of Gut Permeability |
— | — |
| SECONDARY Survival |
97; 85; 81; 68 | — |
| SECONDARY Transplant Free Survival Rate |
88; 64 | — |
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.
Eligibility Criteria
Inclusion Criteria
- AH, as defined by the NIAAA pan-consortia for AH:
- Onset of jaundice (defined as serum total bilirubin >3 mg/dL) within the prior 8 weeks to screening visit
- 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
- AST > 50 IU/l
- AST: ALT > 1.5 and both values 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 400 IU/L, AST/ALT ratio 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 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 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.
Data sourced from ClinicalTrials.gov (NCT04072822). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.