Meta-Analysis of Drug Therapy in Patients With Severe Alcoholic Hepatitis

Study Overview
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Brief Summary
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In the specific setting of the evaluation of corticosteroids, pentoxifylline of their combination in severe alcoholic hepatitis, only meta-analysis combining individual data is able to provide detailed information from each individual with severe alcoholic hepatitis assessed by a DF ≥ 32. The need for such an approach is confirmed by the fact that in both univariate and multivariate analyses, truth survival is lower for conclusions from meta-analysis of the literature than for conclusions derived from non-meta-analyses. The present study is a meta-analysis of individual data from RCTs restricted to patients with a DF ≥ 32. The primary endpoint will be to compare 28-day survival of patients receiving either corticosteroids, or pentoxifylline or their combination to those of patients not receiving them adjusted on the independent prognostic factors at baseline. The secondary endpoints will be: a) assessment of response to the assigned treatment using the Lille model; b) analysis of 6-month survival according to allocated therapy.

Official Title
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Statistical Analysis Plan for an Individual Patient Data Meta-analysis of Ten Clinical Trials Comparing Drug Therapy in Patients With Severe Alcoholic Hepatitis

Conditions
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Alcoholic Hepatitis, Alcoholic Liver Disease

Intervention / Treatment
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* Drug: Pentoxifylline
* Drug: Corticosteroid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients included in 10 randomized controlled trials testing either corticosteroids alone, or pentoxifylline alone or their combination have been published. Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pentoxifylline + Corticosteroid<br>Association of treatment by pentoxifylline and corticosterone during 28 days | Drug: Pentoxifylline<br> <br> Drug: Corticosteroid<br> <br> |
| Corticosteroid<br>treatment by corticosteroid during 28 days | Drug: Corticosteroid<br> <br> Drug: Placebo<br> <br> |
| Pentoxifylline<br>treatment by pentoxifylline during 28 days | Drug: Pentoxifylline<br> <br> Drug: Placebo<br> <br> |
| Placebo<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | at 28 days, after the first administration of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lille Model Score | Lille model evaluate to therapy and will be analyzed as dichotomous outcome (<0.45 vs. ≥0.45), ordinal outcome (≤0.16 vs. 0.16-0.56 vs. ≥ 0.56) and continuous outcome (after log-transformation) and will be restricted to patients with a dosage of bilirubin at day 7 after initiation of assignment treatment. | at day 7, after the first administration of treatment | 
| Biological measure : Bilirubin | evaluate of bilirubin during treatment period | at day 7, at day 28 |