Liver Transplant
Conditions
Keywords
Liver transplant, adults, C2 monitoring
Brief summary
The purpose of this study is to determine whether cyclosporine A (in a micro emulsion formulation) monitored by sample taken 2 hour after oral dose (C-2h) will show equivalent or superior efficacy compared to tacrolimus monitored by pre-dose blood concentration (C-0h). In addition this study will assess the safety and tolerability of a cyclosporine A regimen based on C-2h monitoring in comparison to the standard tacrolimus regimen.
Interventions
DRUGCyclosporine A
DRUGTacrolimus
DRUGBasiliximab
Each patient was given two 20mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery.
DRUGMethylprednisolone
Methylprednisolone was given as an intravenous bolus of 500mg during transplant surgery
DRUGPrednisone
Post-operatively prednisone was tapered from an initial dose of 20mg/day to zero at 3 months or continued at 5-10mg if the indication for Orthotopic Liver Transplantation (OLTx) was of auto-immune nature.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Inclusion criteria
* About to undergo a primary liver transplant (including living donor, non-heart beating donor and split liver). * Age between 18 and 75 years. * Expected to be able to receive the first oral dose of CNI within the first 24 hours post-transplantation (Tx)
Exclusion criteria
* This is a multi-organ transplant or if the patient has previously been transplanted with any other organ. * Urine production is \<200 ml within 12 hours after reperfusion of the graft * Severe coexisting disease is present or if any unstable medical condition is present which could affect the study objectives. Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Occurrence of Biopsy Proven Acute Rejection (BPAR) During the First 3 Months Post de Novo Liver Transplantation. | Month 3 | A BPAR is defined when the investigator had a suspicion of an acute rejection, where the final clinical diagnosis confirmed the occurrence of an acute rejection, where a biopsy was performed that confirmed the presence of an acute rejection, and where anti-rejection treatment intervention was initiated. The efficacy measured the first rejections (clinically and biopsy proven rejections) at 3 months. |
Countries
Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cyclosporine A Cyclosporine A was given twice-daily at 12-hour intervals. It was administered within the first 4 hours post-operatively (study day 1), at an initial dose of 10-15mg/kg/day in two doses. Cyclosporine A was adjusted to bring the 2 hour after oral dose (C-2h) level into the target range by Days 3-5 post-transplantation. The dose of Cyclosporine A was adjusted to achieve and maintain post transplantation C-2h levels 0- 3 months: 800- 1200 ng/mL, 4- 6 months: 700- 900 ng/mL and \>6 months: 500- 700 ng/mL. Each participant was given two 20 mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery. Methylprednisolone was given as an intravenous bolus of 500 mg during transplant surgery. Post-operatively prednisone was tapered from an initial dose of 20 mg/day to zero at 3 months or continued at 5-10 mg if the indication for Orthotopic Liver Transplantation (OLTx) was of auto-immune nature. | 84 |
| Tacrolimus Tacrolimus was given twice-daily at 12-hour intervals. Tacrolimus was administered within the first 24 hrs post- operatively (Study Day 1) at an initial dose of 0.1-0.15 mg/kg/day in two divided oral doses either by mouth or via an enteral feeding tube until the participant can swallow. The initial dosing level was determined by the participants's overall post-operative condition. The dose of tacrolimus was adjusted to achieve and maintain the pre-dose C-Oh (trough) target ranges post-transplantation 0-3 months: 10-15 ng/ml; 4-6 months: 5-10 ng/ml and \> 6 months: 5-10 ng/ml . Each participant was given two 20 mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery. Methylprednisolone was given as an intravenous bolus of 500 mg during transplant surgery. Post-operatively prednisone was tapered from an initial dose of 20 mg/day to zero at 3 months or continued at 5-10 mg if the indication for OLTx was of auto-immune in nature. | 85 |
| Total | 169 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative problems: | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Cyclosporine A | Tacrolimus | Total |
|---|---|---|---|
| Age Continuous | 48.1 Years STANDARD_DEVIATION 12.069 | 49.9 Years STANDARD_DEVIATION 9.886 | 48.98 Years STANDARD_DEVIATION 11.029 |
| Sex: Female, Male Female | 31 Participants | 30 Participants | 61 Participants |
| Sex: Female, Male Male | 53 Participants | 55 Participants | 108 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 84 / 86 | 85 / 85 |
| serious Total, serious adverse events | 42 / 86 | 33 / 85 |
Outcome results
Primary
Percentage of Participants With an Occurrence of Biopsy Proven Acute Rejection (BPAR) During the First 3 Months Post de Novo Liver Transplantation.
A BPAR is defined when the investigator had a suspicion of an acute rejection, where the final clinical diagnosis confirmed the occurrence of an acute rejection, where a biopsy was performed that confirmed the presence of an acute rejection, and where anti-rejection treatment intervention was initiated. The efficacy measured the first rejections (clinically and biopsy proven rejections) at 3 months.
Time frame: Month 3
Population: Intention to treat (ITT) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cyclosporine A | Percentage of Participants With an Occurrence of Biopsy Proven Acute Rejection (BPAR) During the First 3 Months Post de Novo Liver Transplantation. | 33.3 Percentage of Participants |
| Tacrolimus | Percentage of Participants With an Occurrence of Biopsy Proven Acute Rejection (BPAR) During the First 3 Months Post de Novo Liver Transplantation. | 32.9 Percentage of Participants |