Liver Transplant
Conditions
Keywords
Ischemic Cholangiography
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.
Interventions
DRUGFenofibrate
160mg once daily orally for 12 weeks
Sponsors
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability of Fenofibrate | 12 weeks | Proportion of subjects to discontinue fenofibrate due to adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Fenofibrate | 12 weeks | Proportion of subjects with a new grade 3 or 4 adverse event |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Recipients of DCD liver transplants Subjects that underwent transplant of a liver donation after circulatory death (DCD) in the last 21-35 days received a 12 week fenofibrate (Lofibra) for a duration of 12 weeks
Fenofibrate: 160mg once daily orally for 12 weeks | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible due to disease progression | 1 |
Baseline characteristics
| Characteristic | Recipients of DCD liver transplants |
|---|---|
| Age, Continuous | 60.5 years STANDARD_DEVIATION 9.87 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Tolerability of Fenofibrate
Proportion of subjects to discontinue fenofibrate due to adverse events
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recipients of DCD liver transplants | Tolerability of Fenofibrate | 0 Participants |
Secondary
Efficacy of Fenofibrate
Incidence of ischemic cholangiopathy in those treated with 12 weeks of fenofibrate, compared to a historical control group
Time frame: 12 weeks
Population: The historical cohort was not constructed due to inadequate enrollment of the treatment arm
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recipients of DCD liver transplants | Efficacy of Fenofibrate | 0 Participants |
Secondary
Safety of Fenofibrate
Proportion of subjects with acute cellular rejection during fenofibrate treatment
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recipients of DCD liver transplants | Safety of Fenofibrate | 0 Participants |
Secondary
Safety of Fenofibrate
Proportion of subjects myopathy confirmed by serum creatine kinase elevation
Time frame: 16 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recipients of DCD liver transplants | Safety of Fenofibrate | 0 Participants |
Secondary
Safety of Fenofibrate
Mean change in calculated glomerular filtration rate before, during and after fenofibrate treatment
Time frame: Baseline, treatment weeks 4, 8, 12, and at 4 weeks after end of treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recipients of DCD liver transplants | Safety of Fenofibrate | Baseline | 75.3 mL/min/1.73m^2 | Standard Deviation 13 |
| Recipients of DCD liver transplants | Safety of Fenofibrate | Treatment Week 4 | 62.7 mL/min/1.73m^2 | Standard Deviation 24.2 |
| Recipients of DCD liver transplants | Safety of Fenofibrate | Treatment Week 8 | 62.2 mL/min/1.73m^2 | Standard Deviation 26.5 |
| Recipients of DCD liver transplants | Safety of Fenofibrate | Treatment Week 12 | 51.4 mL/min/1.73m^2 | Standard Deviation 21.7 |
| Recipients of DCD liver transplants | Safety of Fenofibrate | Post Treatment Week 4 | 60.5 mL/min/1.73m^2 | Standard Deviation 19.6 |
Secondary
Safety of Fenofibrate
Proportion of subjects with a new grade 3 or 4 adverse event
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recipients of DCD liver transplants | Safety of Fenofibrate | 0 Participants |
Secondary
The Number of Participants Who Developed Ischemic Cholangiopathy (IC)
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.
Time frame: 12 weeks
Population: No participant developed ischemic cholangiopathy, precluding analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recipients of DCD liver transplants | The Number of Participants Who Developed Ischemic Cholangiopathy (IC) | 0 Participants |
| Liver transplant patients not treated with fenofibrate (historical cohort) | The Number of Participants Who Developed Ischemic Cholangiopathy (IC) | 0 Participants |
| Total bile acid level | The Number of Participants Who Developed Ischemic Cholangiopathy (IC) | 0 Participants |
| Fibroblast growth factor-19 level | The Number of Participants Who Developed Ischemic Cholangiopathy (IC) | 0 Participants |
| 7-alpha-hydroxy-cholesten-4 level | The Number of Participants Who Developed Ischemic Cholangiopathy (IC) | 0 Participants |