Liver Preservation for Transplant, Liver Transplantation
Conditions
Brief summary
A prospective, phased-pivotal, international randomized trial to evaluate the effectiveness of the OCS™ Liver to preserve and assess donor livers intended for transplantation.
Detailed description
The OCS™ Liver PROTECT Trial is a two-armed, multicenter, prospective, randomized, controlled pivotal trial to evaluate the effectiveness and safety of the OCS Liver to preserve and assess donor livers intended for transplantation.
Interventions
DEVICEOCS™ Liver System
OTHERControl
Sponsors
TransMedics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Registered male or female primary Liver transplant candidate * Age ≥18 years old * Signed: 1) written informed consent document and 2) authorization to use and disclose protected health information
Exclusion criteria
* Acute, fulminant liver failure * Prior solid organ or bone marrow transplant * Chronic use of hemodialysis or diagnosis of chronic renal failure, defined as chronic serum creatinine of \>3 mg/dl for \>2 weeks and/or requiring hemodialysis * Multi-organ transplant * Ventilator dependent * Dependent on \> 1 IV inotrope to maintain hemodynamics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Early Liver Allograft Dysfunction (EAD) | 7 days | Participants with Early liver Allograft Dysfunction (EAD) or primary non-function, defined as presence of one or more of the following criteria: AST level \> 2000 IU/ml within the first 7 postoperative days; Bilirubin ≥ 10 mg/dl on postoperative day 7; INR ≥ 1.6 on postoperative day 7; or Primary non-functioning graft within the first 7 days (defined as irreversible graft dysfunction requiring emergency liver re-transplantation or death, in the absence of immunologic or surgical causes) |
| Primary Safety Endpoint: Liver Graft-related Serious Adverse Events (LGRSAEs) up to 30-days Post-transplant Per Patient | 30 days | Defined as the average number of LGRSAEs (Liver Graft-Related Serious Adverse Event) up to the 30-day follow-up after transplantation per patient. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Survival at Day 30 After Transplant | 30 days after transplant | Patient survival at day 30 after transplantation |
| Patient Survival at Initial Hospital Discharge Post Liver Transplant | at initial hospital discharge post liver transplant, an average of 11 days | Patient survival at initial hospital discharge post liver transplantation |
Other
| Measure | Time frame | Description |
|---|---|---|
| Evidence of Ischemic Biliary Complications Diagnosed at 6 Months | 6 months post transplant | Number and percentage of Participants with Ischemic Biliary Complications from Day of Transplant through 6 Months Follow-up Visit |
| Evidence of Ischemic Biliary Complications Diagnosed at 12 Months | 12 months post transplant | Number and percentage of Participants with Ischemic Biliary Complications from Day of Transplant through 12 Months Follow-up Visit |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OCS Liver Organ Care System (OCS) Liver | 153 |
| Control Ischemic cold storage (ICS) | 146 |
| Total | 299 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 9 | 9 |
| Overall Study | Died in operating room prior to transplant | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 4 |
| Overall Study | Treated without randomization | 1 | 0 |
Baseline characteristics
| Characteristic | OCS Liver | Control | Total |
|---|---|---|---|
| Age, Continuous | 57.07 years STANDARD_DEVIATION 10.332 | 58.59 years STANDARD_DEVIATION 10.043 | 57.81 years STANDARD_DEVIATION 10.204 |
| Body Mass Index | 29.67 kg/m^2 STANDARD_DEVIATION 5.383 | 29.51 kg/m^2 STANDARD_DEVIATION 5.513 | 29.59 kg/m^2 STANDARD_DEVIATION 5.438 |
| DCD age <=55 years | 28 Participants | 13 Participants | 41 Participants |
| Donor Age | 45.84 years STANDARD_DEVIATION 14.904 | 46.96 years STANDARD_DEVIATION 15.223 | 46.39 years STANDARD_DEVIATION 15.046 |
| Donor age >= 40 years | 102 Participants | 93 Participants | 195 Participants |
| Donor total cross-clamp time >= 6 hours | 48 Participants | 56 Participants | 104 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 20 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 123 Participants | 119 Participants | 242 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 7 Participants | 18 Participants |
| Model for End-stage Liver Disease (MELD) Score | 28.4 scores on a scale STANDARD_DEVIATION 6.9 | 28.0 scores on a scale STANDARD_DEVIATION 5.71 | 28.2 scores on a scale STANDARD_DEVIATION 6.34 |
| Primary Diagnosis Alcoholic cirrhosis | 54 Participants | 48 Participants | 102 Participants |
| Primary Diagnosis Cholestatic diseases | 9 Participants | 8 Participants | 17 Participants |
| Primary Diagnosis Chronic hepatitis | 27 Participants | 36 Participants | 63 Participants |
| Primary Diagnosis Metabolic diseases | 6 Participants | 6 Participants | 12 Participants |
| Primary Diagnosis NASH | 24 Participants | 20 Participants | 44 Participants |
| Primary Diagnosis Other | 19 Participants | 13 Participants | 32 Participants |
| Primary Diagnosis Primary hepatic tumors | 14 Participants | 15 Participants | 29 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 8 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 4 Participants | 13 Participants |
| Race (NIH/OMB) White | 129 Participants | 131 Participants | 260 Participants |
| Sex: Female, Male Female | 51 Participants | 46 Participants | 97 Participants |
| Sex: Female, Male Male | 102 Participants | 100 Participants | 202 Participants |
| Steatotic liver >0% and <=40% macrosteatosis | 95 Participants | 86 Participants | 181 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 9 / 153 | 10 / 147 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 82 / 153 | 72 / 146 |
Outcome results
Primary
Participants With Early Liver Allograft Dysfunction (EAD)
Participants with Early liver Allograft Dysfunction (EAD) or primary non-function, defined as presence of one or more of the following criteria: AST level \> 2000 IU/ml within the first 7 postoperative days; Bilirubin ≥ 10 mg/dl on postoperative day 7; INR ≥ 1.6 on postoperative day 7; or Primary non-functioning graft within the first 7 days (defined as irreversible graft dysfunction requiring emergency liver re-transplantation or death, in the absence of immunologic or surgical causes)
Time frame: 7 days
Population: 1 subject in each arm (OCS Liver and Control) has missing data and therefore the overall number of participants analyzed is different than the number reported in the Participant Flow.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OCS Liver - Per Protocol | Participants With Early Liver Allograft Dysfunction (EAD) | 27 Participants |
| Control - Per-protocol | Participants With Early Liver Allograft Dysfunction (EAD) | 44 Participants |
| OCS Liver - mITT | Participants With Early Liver Allograft Dysfunction (EAD) | 27 Participants |
| Control - mITT | Participants With Early Liver Allograft Dysfunction (EAD) | 47 Participants |
p-value: <0.0001one-sided Farrington and Manning
p-value: <0.0001one-sided Farrington and Manning
Primary
Primary Safety Endpoint: Liver Graft-related Serious Adverse Events (LGRSAEs) up to 30-days Post-transplant Per Patient
Defined as the average number of LGRSAEs (Liver Graft-Related Serious Adverse Event) up to the 30-day follow-up after transplantation per patient.
Time frame: 30 days
Population: As Treated Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OCS Liver - Per Protocol | Primary Safety Endpoint: Liver Graft-related Serious Adverse Events (LGRSAEs) up to 30-days Post-transplant Per Patient | 0.046 Events per patient | Standard Deviation 0.21 |
| Control - Per-protocol | Primary Safety Endpoint: Liver Graft-related Serious Adverse Events (LGRSAEs) up to 30-days Post-transplant Per Patient | 0.075 Events per patient | Standard Deviation 0.265 |
p-value: <0.000195% CI: [-0.084, 0.025]t-test, 1 sided
Secondary
Patient Survival at Day 30 After Transplant
Patient survival at day 30 after transplantation
Time frame: 30 days after transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OCS Liver - Per Protocol | Patient Survival at Day 30 After Transplant | 150 Participants |
| Control - Per-protocol | Patient Survival at Day 30 After Transplant | 141 Participants |
| OCS Liver - mITT | Patient Survival at Day 30 After Transplant | 151 Participants |
| Control - mITT | Patient Survival at Day 30 After Transplant | 145 Participants |
p-value: 0.0004one-sided Farrington and Manning
p-value: 0.0004one-sided Farrington and Manning
Secondary
Patient Survival at Initial Hospital Discharge Post Liver Transplant
Patient survival at initial hospital discharge post liver transplantation
Time frame: at initial hospital discharge post liver transplant, an average of 11 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OCS Liver - Per Protocol | Patient Survival at Initial Hospital Discharge Post Liver Transplant | 149 Participants |
| Control - Per-protocol | Patient Survival at Initial Hospital Discharge Post Liver Transplant | 140 Participants |
| OCS Liver - mITT | Patient Survival at Initial Hospital Discharge Post Liver Transplant | 150 Participants |
| Control - mITT | Patient Survival at Initial Hospital Discharge Post Liver Transplant | 144 Participants |
p-value: 0.0006one-sided Farrington and Manning
p-value: 0.0006one-sided Farrington and Manning
Other Pre-specified
Evidence of Ischemic Biliary Complications Diagnosed at 12 Months
Number and percentage of Participants with Ischemic Biliary Complications from Day of Transplant through 12 Months Follow-up Visit
Time frame: 12 months post transplant
Population: per-protocol population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OCS Liver - Per Protocol | Evidence of Ischemic Biliary Complications Diagnosed at 12 Months | 4 Participants |
| Control - Per-protocol | Evidence of Ischemic Biliary Complications Diagnosed at 12 Months | 14 Participants |
Other Pre-specified
Evidence of Ischemic Biliary Complications Diagnosed at 6 Months
Number and percentage of Participants with Ischemic Biliary Complications from Day of Transplant through 6 Months Follow-up Visit
Time frame: 6 months post transplant
Population: per-protocol population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| OCS Liver - Per Protocol | Evidence of Ischemic Biliary Complications Diagnosed at 6 Months | 2 Participants |
| Control - Per-protocol | Evidence of Ischemic Biliary Complications Diagnosed at 6 Months | 12 Participants |