A Study to Assess the Role of Fenofibrate in Preventing Ischemic Cholangiopathy After Liver Transplantation

Phase 2

Terminated

Brief Summary: The purpose of this study is to evaluate the safety and effectiveness of a once-daily medication, fenofibrate (Lofibra), to prevent ischemic cholangiography (IC) in persons who were transplanted with livers donated after circulatory death (DCD).

Detailed Description: In this prospective pilot study, we aim to evaluate 1) the tolerability and safety, 2) the efficacy of 12 weeks once-daily fenofibrate in reducing IC incidence after DCD liver transplantation, 3) assess the association between serum markers of cholestasis and development of IC.

Recruitment & Eligibility

Inclusion Criteria

Patients who have undergone Donation after Circulatory Death (DCD) liver transplantation (LT).
At least one serum alkaline phosphatase level >2.5x upper limit of normal between post-LT days 21-60 (inclusive).

Exclusion criteria:

LT performed for primary sclerosing cholangitis or primary biliary cholangitis.
Untreated hepatic artery compromise (e.g thrombosis, stenosis)
Untreated biliary anastomotic stricture or bile leak between days 0-60 after LT
Renal dysfunction defined as baseline glomerular filtration rate < 30 ml/min.
Previously known intolerance or allergy to fenofibrate.
Other clinically significant comorbid condition, including psychiatric conditions, which in the opinion of the study team, may interfere with patient treatment, safety, assessment, or compliance with the treatment.
Adults lacking capacity to consent to treatment

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Recipients of DCD liver transplants	Fenofibrate	Subjects that have undergone transplant of a liver donation after circulatory death (DCD) in the last 21-35 days will receive a 12 week fenofibrate (Lofibra) for a duration of 12 weeks

Primary Outcome Measures

Name	Time	Method
Tolerability of Fenofibrate	12 weeks	Proportion of subjects to discontinue fenofibrate due to adverse events

Secondary Outcome Measures

Name	Time	Method
Safety of Fenofibrate	16 weeks	Proportion of subjects myopathy confirmed by serum creatine kinase elevation
Efficacy of Fenofibrate	12 weeks	Incidence of ischemic cholangiopathy in those treated with 12 weeks of fenofibrate, compared to a historical control group
The Number of Participants Who Developed Ischemic Cholangiopathy (IC)	12 weeks	The number of participants who developed IC was assessed by measuring serum alkaline phosphatase, gamma glutamyl transferase, total bile acid level, fibroblast growth factor 19 level, and 7-alpha-hydroxy-cholesten-4 levels. Logistics regression was used to calculate the changes in serum alkaline phosphatase, gamma glutamyl transferase, total bile acid level, fibroblast growth factor 19 level, and 7-alpha-hydroxy-cholesten-4 and estimate the probability that a participant had developed IC. The probability can range from 0 (no development of IC) to 1 (development of IC), with a higher number indicating a worse outcome.