Liver Transplantation
Conditions
Keywords
calcineurin inhibitor delay, Kidney
Brief summary
This study will evaluate the use of a drug called Thymoglobulin, combined with a delayed start of the anti-rejection drugs (10 days after liver transplant), compared to the current approach of starting anti-rejection drugs called calcineurin inhibitors or CNI's within 2 days after the liver transplant.
Detailed description
Strong anti-rejection drugs like tacrolimus or cyclosporine, are given to patients who have received transplants, to ensure that the patient's body does not reject the new organ. In some cases, while anti-rejection medications protect a newly transplanted liver, they can injure the patient's kidneys and cause them not to work as well as they should. The purpose of this pilot study is to determine the best way to protect kidney function and to ensure that the newly transplanted liver is not rejected. This study will evaluate the use of a drug called Thymoglobulin, combined with a delayed start of the anti-rejection drugs (10 days after liver transplant), compared to the current approach of starting anti-rejection drugs called calcineurin inhibitors or CNI's within 2 days after the liver transplant.
Interventions
BIOLOGICALThymoglobulin 3mg total
1.5 mg/kg induction on Day 0 and 1.5 mg/kg induction on Day 2 (total of 3 mg/kg)
BIOLOGICALThymoglobulin 4.5mg total
1.5 mg/kg induction on Days 0, 2 and 4 (total 4.5 mg/kg)
DRUGMycophenolate mofetil
1000 mg PO/IV BID for up to 6 months
DRUGtacrolimus 3-8
Trough concentration between 3 ng/mL and 8 ng/mL starting on Day 10 and continuing beyond Day 180
DRUGtacrolimus 8-12
Trough concentration between 8 ng/mL and 12 ng/mL on Days 0-10; between 6 ng/mL and 12 ng/mL on Days 10-30; between 6 ng/mL and 10 ng/mL Days 31-60; between 5 ng/mL and 8 ng/mL Days 61-179; and between 3 ng/mL and 8 ng/mL beyond Day 180.
Sponsors
Genzyme, a Sanofi Company
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients undergoing deceased donor solitary liver transplantation * Adults aged 18-70 at time of transplantation * Hepatocellular carcinoma as indication for OLT within the Milan Criteria * Hepatitis C positive or negative patients * Willingness to comply with study procedures * Able to sign informed consent
Exclusion criteria
* Prior kidney transplantation * Congenital or iatrogenic absence of one kidney * Subjects on renal replacement therapy at the time of OLT * MELD score \> 28 * HIV positive patient * Patient with current severe systemic infection * History of bacterial peritonitis within 30 days prior to OLT * Active infection or recent infection within 30 days prior to OLT * Use of calcineurin inhibitor continuously for more than 90 days within the past 6 months * History of hypersensitivity to thymoglobulin, rabbits, tacrolimus or iohexol * Women of childbearing age who are unwilling to use effective contraceptive methods during the duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estimated Glomerular Filtration Rate (eGFR) at 12 Months Post-surgery | 12 Months | Postoperative acute kidney injury is measured as reduced (eGFR) within 12 months post-surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Survival | 12 months post-transplant | — |
| Graft Survival | 12 months post transplant | 90% graft survival, related to the deaths of 3 patients during the study period. |
| Allograft Rejection Rates at 30 Days | 30 days | Acute Allograft Rejection |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Delayed CNI Group 1 Thymoglobulin 3mg total, administered on Days 0 and 2 (after transplant), plus MMF and corticosteroids. CNI administration delayed until 10 days post transplant. tacrolimus 3-8 (trough concentration)
Thymoglobulin 3mg total: 1.5 mg/kg induction on Day 0 and 1.5 mg/kg induction on Day 2 (total of 3 mg/kg)
Mycophenolate mofetil: 1000 mg PO/IV BID for up to 6 months
tacrolimus 3-8: Trough concentration between 3 ng/mL and 8 ng/mL starting on Day 10 and continuing beyond Day 180 | 10 |
| Delayed CNI Group 2 Thymoglobulin 4.5mg total, plus MMF and corticosteroids. CNI therapy delayed until 10 days post transplant.tacrolimus 3-8 (trough concentration)
Thymoglobulin 4.5mg total: 1.5 mg/kg induction on Days 0, 2 and 4 (total 4.5 mg/kg)
Mycophenolate mofetil: 1000 mg PO/IV BID for up to 6 months
tacrolimus 3-8: Trough concentration between 3 ng/mL and 8 ng/mL starting on Day 10 and continuing beyond Day 180 | 10 |
| Early CNI / Control Arm Standard post liver transplant therapy to include: tacrolimus 8-12 (trough concentration) initiated within 48 hours post-transplant, plus mycophenolate mofetil (MMF) and corticosteroids to be administered within 24 hours after transplant (Day 0).
Mycophenolate mofetil: 1000 mg PO/IV BID for up to 6 months
tacrolimus 8-12: Trough concentration between 8 ng/mL and 12 ng/mL on Days 0-10; between 6 ng/mL and 12 ng/mL on Days 10-30; between 6 ng/mL and 10 ng/mL Days 31-60; between 5 ng/mL and 8 ng/mL Days 61-179; and between 3 ng/mL and 8 ng/mL beyond Day 180. | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | Total | Delayed CNI Group 2 | Early CNI / Control Arm | Delayed CNI Group 1 |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 9 Participants | 10 Participants | 9 Participants |
| Race and Ethnicity Not Collected | 0 Participants | — | — | — |
| Region of Enrollment United States | 30 Participants | 10 Participants | 10 Participants | 10 Participants |
| Sex: Female, Male Female | 6 Participants | 1 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 24 Participants | 9 Participants | 7 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 1 / 10 | 2 / 10 |
| other Total, other adverse events | 2 / 10 | 5 / 10 | 4 / 10 |
| serious Total, serious adverse events | 0 / 10 | 1 / 10 | 1 / 10 |
Outcome results
Primary
Estimated Glomerular Filtration Rate (eGFR) at 12 Months Post-surgery
Postoperative acute kidney injury is measured as reduced (eGFR) within 12 months post-surgery.
Time frame: 12 Months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Delayed CNI Group 1 | Estimated Glomerular Filtration Rate (eGFR) at 12 Months Post-surgery | 72 mL/min |
| Delayed CNI Group 2 | Estimated Glomerular Filtration Rate (eGFR) at 12 Months Post-surgery | 87.8 mL/min |
| Early CNI / Control Arm | Estimated Glomerular Filtration Rate (eGFR) at 12 Months Post-surgery | 51.0 mL/min |
Secondary
Allograft Rejection Rates at 30 Days
Acute Allograft Rejection
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Delayed CNI Group 1 | Allograft Rejection Rates at 30 Days | 3 Participants |
| Delayed CNI Group 2 | Allograft Rejection Rates at 30 Days | 1 Participants |
| Early CNI / Control Arm | Allograft Rejection Rates at 30 Days | 0 Participants |
Secondary
Graft Survival
90% graft survival, related to the deaths of 3 patients during the study period.
Time frame: 12 months post transplant
Population: Kaplan Meier for patient survival
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Delayed CNI Group 1 | Graft Survival | 10 Participants |
| Delayed CNI Group 2 | Graft Survival | 9 Participants |
| Early CNI / Control Arm | Graft Survival | 8 Participants |
Secondary
Patient Survival
Time frame: 12 months post-transplant
Population: Kaplan- Meier
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Delayed CNI Group 1 | Patient Survival | 10 Participants |
| Delayed CNI Group 2 | Patient Survival | 9 Participants |
| Early CNI / Control Arm | Patient Survival | 8 Participants |