- Louvet A.
- Thursz M.R.
- Kim D.J.
- Labreuche J.
- Atkinson S.R.
- Sidhu S.S.
- et al.
Pathophysiology of AH
Novel agents in the management of severe alcoholic hepatitis
|Pharmaceutical agent||Mechanism of action||Study design|
|Main inclusion||Primary endpoint||Status|
|Bovine colostrum (IMM-124E)||IgG to LPS and reduces bacterial translocation||Placebo controlled RCT||MELD score ≥20 but ≤28||Decrease in serum endotoxin levels at 7 months||Phase II, active, not recruiting|
|Lactobacillus rhamnosus GG||Change in gut microbiome||Placebo controlled RCT||MELD score <21||Change in MELD score at 30 days||Phase II, active and recruiting|
|Augmentin||Antibiotic amoxicillin plus clavulanic acid||Placebo controlled RCT with CS||MELD score ≥21||Survival at 2 months||Phase III, active and recruiting|
|Faecal transplant||Change in gut microbiome||RCT FMT vs. CS||Eligible for CS treatment||Survival at 3 months||Active and recruiting|
|Anakinra||Antagonist to IL-1 receptor||RCT Anakinra + Zn + PTX vs. CS||MELD score ≥20 and Madre DF ≥32||Survival at 6 months||Phase II, active and recruiting|
|Obeticholic acid [INT-747]||FXR activation, bile acid agonist, and anti-inflammatory||Placebo controlled RCT||MELD score >11 and <20||Change in MELD score at 6 weeks||Phase II, completed|
|ASK-1 antagonist to inhibit MAPK, JNK, p38||Placebo controlled RCT with CS||Maddrey DF score ≥32||Safety and SAE at 28 days plus 30 days||Phase II, completed|
|Pan caspase inhibitor||Placebo controlled RCT||MELD score >20 but <35 or 35–40 if SOFA score <10||Survival at 28 days||Phase II, terminated after 5 patients|
|Metadoxine||Antioxidant and promotes abstinence||Placebo controlled RCT with CS||Severe alcoholic hepatitis||Survival at 30 days||Phase IV, completed|
|Anti-inflammatory and hepatic regeneration||Open label||MELD score 11–28||Safety and SAE at 42 days||Phase I completed|
Phase II planned
|Increase neutrophils, hepatic regeneration||Placebo controlled RCT with CS in partial responder and without CS in null responder||Maddrey DF score ≥32||Survival at 2 months in null responder to CS and at 6 months in partial responder||Phase IV, active and recruiting|
Drugs acting on the gut-liver axis
- Vergis N.
- Atkinson S.R.
- Knapp S.
- Maurice J.
- Allison M.
- Austin A.
- et al.
Drugs acting as anti-inflammatory agents
- Opal S.M.
- Fisher Jr., C.J.
- Dhainaut J.F.
- Vincent J.L.
- Brase R.
- Lowry S.F.
- et al.
Drugs acting on the regenerative pathway
Drugs acting as antioxidants
Lessons learnt from the STOPAH study: Current clinical trial design
Corticosteroids or placebo in the control arm
General treatment and candidacy for liver transplantation in the two arms
Disease severity for patient recruitment
Combining pharmacological therapies
Timing of endpoint on patient survival
Pharmacokinetics and safety data with phase I trials
Liver biopsy for patient recruitment
Conflict of interest
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