Evidence of Liver Transplantation, Hyperglycemia, Rejection
Conditions
Keywords
Liver, transplantation, Glucose, Hyperglycemia, Insulin, Rejection, Hypoglycemia
Brief summary
Many but not all studies have shown improvement in morbidity and mortality with intensive glycemic management postoperatively. In this study, the investigators propose to determine whether improved glycemic control using intensive insulin treatment immediately postoperatively will improve outcomes in patients undergoing liver transplant using a prospective, controlled, randomized, parallel-group study design targeting two different glucose levels, 140 and 180 mg/dL.
Detailed description
Many studies have shown improvement in morbidity and mortality with intensive glycemic management postoperatively. However, some recent studies have not been able to reproduce these benefits and have raised the issue of adverse consequences of hypoglycemia associated with intensive therapy. Our own data show an association of increased graft rejection proportional to postoperative glucose levels in patients who have undergone a liver transplant. Preliminary data suggest that this may improved by better glycemic control using the Glucose Management Service here at Northwestern. In this study, we propose to determine whether improved glycemic control using intensive insulin treatment immediately postoperatively will improve outcomes in patients undergoing liver transplant using a prospective, controlled, randomized, parallel-group study design targeting two different glucose levels, 140 and 180 mg/dL. Postoperative glucose management with insulin will be supervised by the Glucose Management Service as is routine, with the only research aspect being the two different glucose targets and the outcome analysis with liver transplant rejection as the primary outcome and infections and hypoglycemia being the principle secondary outcomes.
Interventions
DRUGInsulin
Insulin initially as continuous infusion for first 24-48 hours followed by subcutaneous administration once subjects eating and out of intensive care unit.
Sponsors
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Require Liver Transplantation 2. Age 18 - 80 3. Able to give informed consent personally or via a family member who has appropriate authorization to do so if patient unconscious. 4. Expected survival following transplantation for \> 1 year. 5. Glucose level over 180 mg/dL postoperatively
Exclusion criteria
1. Inability of patient or family member to give informed consent 2. Not expected to survive for \> 1 year following liver transplantation. 3. Previous liver transplantation 4. Acute liver failure 5. Living related donor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rejection of Liver Transplant | within 1 year of transplantation | Liver transplant rejection determined by either biopsy or clinical criteria (\>2x transaminases, clinical decision, treatment with high dose steroids and other anti-rejection medications |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hypoglycemia | Within first 3 days following transplantation | Participants experiencing hypoglycemia (glucose \< 70 mg/dL) within the first 3- days following transplantation |
| Infection Rates | Within 1 year following transplantation | — |
| Rehospitalization Rates | Within 1 year following transplantation | — |
| Overall Graft Survival at 1 Year | 1 year following transplantation | — |
| Death Within 1 Year | 1 year | Death following liver transplant between 1 day and 1 year |
Countries
United States
Participant flow
Recruitment details
Patients were primarily recruited from Liver Transplant Clinic and the inpatient Liver Transplant service
Pre-assignment details
Of 278 patients Consented, 46 died before transplant, 38 did not undergo transplant, 14 were delisted for transplant, and 16 did not enter the study for miscellaneous reasons.
Participants by arm
| Arm | Count |
|---|---|
| 140 Group Insulin treatment to target blood glucose at 140 mg/dl
Insulin: Insulin initially as continuous infusion for first 24-48 hours followed by subcutaneous administration once subjects eating and out of intensive care unit. | 82 |
| 180 Group Insulin treatment to target blood glucose at 180 mg/dl
Insulin: Insulin initially as continuous infusion for first 24-48 hours followed by subcutaneous administration once subjects eating and out of intensive care unit. | 82 |
| Total | 164 |
Baseline characteristics
| Characteristic | 140 Group | 180 Group | Total |
|---|---|---|---|
| Age, Continuous | 58.1 years STANDARD_DEVIATION 8 | 56.9 years STANDARD_DEVIATION 7.6 | 57.5 years STANDARD_DEVIATION 7.8 |
| body mass index | 30.3 kg/m^2 STANDARD_DEVIATION 6 | 30.0 kg/m^2 STANDARD_DEVIATION 6.6 | 30.1 kg/m^2 STANDARD_DEVIATION 6.3 |
| Gender Female | 29 Participants | 29 Participants | 58 Participants |
| Gender Male | 53 Participants | 53 Participants | 106 Participants |
| Hepatitis C positive Hepatitis C Negative | 46 participants | 50 participants | 96 participants |
| Hepatitis C positive Hepatitis C Positive | 36 participants | 32 participants | 68 participants |
| Liver only Transplant Liver Only | 71 participants | 68 participants | 139 participants |
| Liver only Transplant Liver Plus Kidney | 11 participants | 14 participants | 25 participants |
| Model for End-stage Liver DIsease (MELD) Score | 27.3 units on a scale STANDARD_DEVIATION 9.4 | 28.2 units on a scale STANDARD_DEVIATION 7.6 | 27.8 units on a scale STANDARD_DEVIATION 8.6 |
| Race/Ethnicity, Customized Asian | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Black | 6 participants | 9 participants | 15 participants |
| Race/Ethnicity, Customized Caucasian | 57 participants | 63 participants | 120 participants |
| Race/Ethnicity, Customized Hispanic | 15 participants | 7 participants | 22 participants |
| Race/Ethnicity, Customized Unknown | 3 participants | 2 participants | 5 participants |
| Region of Enrollment United States | 82 participants | 82 participants | 164 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 40 / 82 | 62 / 82 |
| serious Total, serious adverse events | 53 / 82 | 56 / 82 |
Outcome results
Primary
Rejection of Liver Transplant
Liver transplant rejection determined by either biopsy or clinical criteria (\>2x transaminases, clinical decision, treatment with high dose steroids and other anti-rejection medications
Time frame: within 1 year of transplantation
Population: Patients undergoing liver transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 140 Group | Rejection of Liver Transplant | 17 participants |
| 180 Group | Rejection of Liver Transplant | 20 participants |
p-value: 0.709Chi-squared, Corrected
Secondary
Death Within 1 Year
Death following liver transplant between 1 day and 1 year
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 140 Group | Death Within 1 Year | 5 participants |
| 180 Group | Death Within 1 Year | 7 participants |
p-value: 0.77Chi-squared, Corrected
Secondary
Hypoglycemia
Participants experiencing hypoglycemia (glucose \< 70 mg/dL) within the first 3- days following transplantation
Time frame: Within first 3 days following transplantation
Population: Patients having liver transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 140 Group | Hypoglycemia | 27 participants |
| 180 Group | Hypoglycemia | 10 participants |
p-value: 0.003Chi-squared, Corrected
Secondary
Infection Rates
Time frame: Within 1 year following transplantation
Population: patients having had liver transplants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 140 Group | Infection Rates | 35 participants |
| 180 Group | Infection Rates | 54 participants |
p-value: 0.0046Chi-squared, Corrected
Secondary
Overall Graft Survival at 1 Year
Time frame: 1 year following transplantation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 140 Group | Overall Graft Survival at 1 Year | 77 participants |
| 180 Group | Overall Graft Survival at 1 Year | 74 participants |
p-value: 0.56Chi-squared, Corrected
Secondary
Rehospitalization Rates
Time frame: Within 1 year following transplantation
Population: patients undergoing liver transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 140 Group | Rehospitalization Rates | 48 participants |
| 180 Group | Rehospitalization Rates | 51 participants |
p-value: 0.75Chi-squared, Corrected