Pegfilgrastim in Patients With Alcoholic Hepatitis

Study Overview
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Brief Summary
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This is a multi-center, prospective, randomized trial of standard of care vs. standard of care + pegfilgrastim (Neulasta®) among patients with a clinical diagnosis of alcoholic hepatitis and DF≥32.

Detailed Description
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Standard of care treatment will be with either prednisolone 40 mg/day for 28 days or pentoxifylline 400 mg TID for 28 days. The patient's physician will decide the standard of care treatment the patient will receive. Patients will be randomized (1:1) to receive either no additional drug treatment (SOC group) or to receive a pegfilgrastim (Neulasta®, 6 mg) SQ. Patients will be seen in-person at screening, randomization (Day 1), Day 8, Day 29, Week 12, and Week 24. Safety examination and blood tests will be performed. In addition, biological specimens will be saved for research purposes at these time points. Total duration of patient participation is 24 weeks.

Official Title
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A Phase II, Multicenter, Randomized, Open-label Study to Investigate the Safety and Efficacy of Pegfilgrastim (Neulasta®) in Patients With Alcoholic Hepatitis

Conditions
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Alcoholic Hepatitis

Intervention / Treatment
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* Drug: Standard of care + pegfiltrastim
* Drug: Standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A clinical diagnosis of alcoholic hepatitis with Maddrey's discriminant function score ≥32. Age 18 years or older. Exclusion Criteria: Renal failure (creatinine >2.0 mg/dl) Bilirubin <5 mg/dL uncontrolled recent upper gastrointestinal bleeding Known HIV infection Uncontrolled infection, or pregnant.

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: prednisolone or pentoxifylline + pegfiltrastim<br>prednisolone or pentoxifylline for 28 days PO plus pegfilgrastim subcutaneous weekly shot | Drug: Standard of care + pegfiltrastim<br>* prednisolone or pentoxifyline orally for 28 days + pegfilgrastim (Neulasta®) 6 mg in 0.6 mL SQ<br>* Other names: Neulasta®;|
| Active Comparator: prednisolone or pentoxifylline<br>prednisolone or pentoxifylline for 28 days | Drug: Standard of care<br>* Oral prednisolone or pentoxifyline for 28 days only<br>* Other names: prednisolone or pentoxifyline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events, especially infection and renal failure, Change in MELD Score and DF between Day 1 and Day 29, Lille score (at Day 8) | The primary outcome will be survival at Day 90. Assuming a fixed sample size of 70 patients (35 per arm), a one-sided z-test will have 81.6% power to detect a 25% improvement in survival proportions between arms, with survival in the standard of care arm at 65%. | Day 1, Day 8, Day 29, and Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse events | adverse events through Week 24 | 24 weeks | 
| Liver function | Change in MELD and Maddrey DF during first 4 weeks | Day 29 | 
| liver function | Change in Lille score | Day 8 | 
| Survival | survival at Day 90 | at Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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survival, pegfilgrastim, cirrhosis, alcoholic