Pegfilgrastim in Patients With Alcoholic Hepatitis

Sponsor

Timothy Morgan, MD (Other)

Overall Status

Completed

CT.gov ID

NCT02776059

Collaborator

National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)

Enrollment

Locations

Arms

50.3

Actual Duration (Months)

6.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Alcoholic Hepatitis	Drug: Standard of care + pegfiltrastim Drug: Standard of care	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 21, 2017

Actual Primary Completion Date :

Mar 31, 2020

Actual Study Completion Date :

Mar 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: prednisolone or pentoxifylline + pegfiltrastim prednisolone or pentoxifylline for 28 days PO plus pegfilgrastim subcutaneous weekly shot	Drug: Standard of care + pegfiltrastim prednisolone or pentoxifyline orally for 28 days + pegfilgrastim (Neulasta®) 6 mg in 0.6 mL SQ Other Names: Neulasta®
Active Comparator: prednisolone or pentoxifylline prednisolone or pentoxifylline for 28 days	Drug: Standard of care Oral prednisolone or pentoxifyline for 28 days only Other Names: prednisolone or pentoxifyline

Arm

Intervention/Treatment

Experimental: prednisolone or pentoxifylline + pegfiltrastim

prednisolone or pentoxifylline for 28 days PO plus pegfilgrastim subcutaneous weekly shot

Drug: Standard of care + pegfiltrastim

prednisolone or pentoxifyline orally for 28 days + pegfilgrastim (Neulasta®) 6 mg in 0.6 mL SQ

Other Names:

Neulasta®

Active Comparator: prednisolone or pentoxifylline

prednisolone or pentoxifylline for 28 days

Drug: Standard of care

Oral prednisolone or pentoxifyline for 28 days only

Other Names:

prednisolone or pentoxifyline

Outcome Measures

Primary Outcome Measures

Adverse events, especially infection and renal failure, Change in MELD Score and DF between Day 1 and Day 29, Lille score (at Day 8) [Day 1, Day 8, Day 29, and Day 90]
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%.

Secondary Outcome Measures

adverse events [24 weeks]
adverse events through Week 24
Liver function [Day 29]
Change in MELD and Maddrey DF during first 4 weeks
liver function [Day 8]
Change in Lille score
Survival [at Day 90]
survival at Day 90

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Loma Linda Healthcare System	Loma Linda	California	United States	92357
2	VA Long Beach Healthcare System	Long Beach	California	United States	98022
3	LAC-USC Medical Center	Los Angeles	California	United States	90089
4	Harbor-UCLA Medical Center	Torrance	California	United States	90502
5	New Mexico VA Health Care System	Albuquerque	New Mexico	United States	87108