Liver Transplant
Conditions
Keywords
liver, transplant, blood sugar
Brief summary
The goal of the proposed study is to evaluate the effectiveness of intraoperative, strict glycemic control to improve survival and infection rates following liver transplantation in a randomized, prospective trial.Primary objective: To determine if strict intraoperative blood glucose control, when compared to standard intraoperative glycemic control, improves 1-year recipient survival and decreases surgical complications, including infections, following liver transplantation.
Detailed description
Approximately 2.1 million patients in the United States acquire infections during medical care every year. For example, 9%-30% patients who undergo surgery acquire nosocomial infections, which increase mortality and morbidity over that expected normally expected and increase the cost of care by several billion dollars. Studies have shown that controlling high blood glucose levels dramatically improves the recovery of critically ill patients after surgery, most notably decreasing the risk of infection. The advantage of strict glycemic control in the critically ill patient is now well accepted, and the Institute for Healthcare Improvement and Surviving Sepsis Campaign set glycemic control as part of the post-operative sepsis management bundle. Few studies have investigated the role of strict glycemic control during surgery itself. Liver transplantation is a good model for studying glucose control as hyperglycemia almost always occurs and the incidence of infection is higher than with other surgical procedures. We performed a retrospective review of 184 consecutive adult liver recipients in which intra-operative blood glucose levels were measured and treated with insulin. Recipients with strict glycemic control were compared to those with poor control for differences in donor and recipient demographics, intra-operative blood glucose concentrations, intra-operative insulin administered, immunosuppression, post-operative complications, and mortality. Poor glycemic control was associated with a significantly increased rate of infection during the first 30 days post-operatively (48% vs. 33%, P=0.05) and 1-year mortality was significantly increased for those recipients with poor intra-operative glucose control (21.9% vs. 8.8%; P = 0.05). These data along with the post-operative studies, suggest that the post-transplant mortality rate may potentially be decreased by nearly 50% at 1 year and underscore the need for this to be confirmed in a prospective trial. The goal of this study is to prospectively evaluate the outcomes of liver transplant recipients to either strict glucose control (goal of 80-110 mg/dl) or the current standard of care (goal of between 180 and 200 mg/dl). The specific aim of this study is to determine if strict intra-operative blood glucose control, improves 1-year recipient survival and decreases surgical complications, including infections, following liver transplantation. The rates of infection at 30 days after surgery and health at one year post- surgery will be compared. The frequency of other common post-operation complications will also be studied. The proposed study has the potential to have an impact on the intra-operative management of all liver transplant recipients.
Interventions
DRUGinsulin
bolus or infusion 80 to 110 mg/dl
Sponsors
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patients ≥ 18 years old undergoing liver transplantation * Patients willing and capable of giving written informed consent for study participation
Exclusion criteria
* Multi-organ transplant recipients * Patients receiving a liver incompatible with A, B or O blood types * HIV infected patients * Recipients of an organ from an HIV+ donor * Patients with severe coexisting disease or presenting with any unstable medical condition which could affect the study objectives * Patients with a co-existing alcoholic disease who have not been abstinent for at least 6 month immediately prior to transplantation and are not expected to be able to remain abstinent after transplantation * Patients who are unlikely to comply with the study requirements or unable to give informed consent * Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer or if such therapy is to be instituted posttransplantation * Patients transplanted for hepatocellular carcinoma exceeding 3 nodules or with nodule diameter larger than 5 cm * History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin * Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadatropin (hCG) laboratory test (\> 5 milli-International units (mIU/ml)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Infection Rates | 30 days | Number of participants who sustained an infection after surgery |
| Number of Participants With One Year Survival Post Transplant | 12 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Need for Hemodialysis | 12 months post surgery | Number of people who had renal failure in the year following liver transplant and needing hemodialysis to support it; |
| Hospital Length of Stay | 12 months | — |
| Number of Participants With Venous Thrombotic Complications | 12 months | Number of participants who were diagnosed with portal vein thrombosis post surgery |
| Number of Participants With Biliary Complications | 12 months | Number of participants who experienced bile leak or biliary Stricture |
| Participants Who Required Postoperative Blood Transfusion Within 3 Days in the ICU | 12 months | Requirements for blood transfusion counted as a binary variable yes/no per participant |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Strict Glycemic Control strict glycemic control (80 to 110 mg/dl)
insulin: bolus or infusion 80 to 110 mg/dl | 50 |
| Standard of Care Control standard of care insulin dosing | 50 |
| Total | 100 |
Baseline characteristics
| Characteristic | Strict Glycemic Control | Total | Standard of Care Control |
|---|---|---|---|
| Age, Continuous | 54 years | 54 years | 55 years |
| BMI | 30.4 kg/m2 | 29.6 kg/m2 | 28.9 kg/m2 |
| Pre-existing conditions Coronary Artery Disease(CAD) | 4 Participants | 8 Participants | 4 Participants |
| Pre-existing conditions Diabetes | 13 Participants | 29 Participants | 16 Participants |
| Race/Ethnicity, Customized African American | 5 Participants | 9 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 8 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 41 Participants | 82 Participants | 41 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 9 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) White | 41 Participants | 82 Participants | 41 Participants |
| Region of Enrollment United States | 50 Participants | 100 Participants | 50 Participants |
| Sex: Female, Male Female | 38 Participants | 74 Participants | 36 Participants |
| Sex: Female, Male Male | 12 Participants | 26 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 50 | 9 / 50 |
| other Total, other adverse events | 45 / 50 | 42 / 50 |
| serious Total, serious adverse events | 16 / 50 | 11 / 50 |
Outcome results
Primary
Infection Rates
Number of participants who sustained an infection after surgery
Time frame: 30 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Strict Glycemic Control | Infection Rates | Bacterial Infection | 27 Participants |
| Strict Glycemic Control | Infection Rates | Fungal Infection | 11 Participants |
| Strict Glycemic Control | Infection Rates | Transplant Incision wound | 9 Participants |
| Strict Glycemic Control | Infection Rates | Viral | 4 Participants |
| Standard of Care Control | Infection Rates | Viral | 6 Participants |
| Standard of Care Control | Infection Rates | Bacterial Infection | 26 Participants |
| Standard of Care Control | Infection Rates | Transplant Incision wound | 7 Participants |
| Standard of Care Control | Infection Rates | Fungal Infection | 7 Participants |
p-value: 0.841Chi-squared
p-value: 0.298Chi-squared
p-value: 0.585Chi-squared
p-value: 0.505Chi-squared
Primary
Number of Participants With One Year Survival Post Transplant
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Strict Glycemic Control | Number of Participants With One Year Survival Post Transplant | 44 Participants |
| Standard of Care Control | Number of Participants With One Year Survival Post Transplant | 44 Participants |
p-value: 0.999Fisher Exact
Secondary
Hospital Length of Stay
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Strict Glycemic Control | Hospital Length of Stay | 12.5 days |
| Standard of Care Control | Hospital Length of Stay | 11 days |
p-value: 0.384Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With a Need for Hemodialysis
Number of people who had renal failure in the year following liver transplant and needing hemodialysis to support it;
Time frame: 12 months post surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Strict Glycemic Control | Number of Participants With a Need for Hemodialysis | 6 Participants |
| Standard of Care Control | Number of Participants With a Need for Hemodialysis | 9 Participants |
p-value: 0.401Fisher Exact
Secondary
Number of Participants With Biliary Complications
Number of participants who experienced bile leak or biliary Stricture
Time frame: 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Strict Glycemic Control | Number of Participants With Biliary Complications | bile leak | 14 Participants |
| Strict Glycemic Control | Number of Participants With Biliary Complications | Biliary Stricture | 13 Participants |
| Standard of Care Control | Number of Participants With Biliary Complications | bile leak | 15 Participants |
| Standard of Care Control | Number of Participants With Biliary Complications | Biliary Stricture | 20 Participants |
p-value: 0.826Chi-squared
p-value: 0.137Chi-squared
Secondary
Number of Participants With Venous Thrombotic Complications
Number of participants who were diagnosed with portal vein thrombosis post surgery
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Strict Glycemic Control | Number of Participants With Venous Thrombotic Complications | 3 Participants |
| Standard of Care Control | Number of Participants With Venous Thrombotic Complications | 3 Participants |
p-value: 0.999Fisher Exact
Secondary
Participants Who Required Postoperative Blood Transfusion Within 3 Days in the ICU
Requirements for blood transfusion counted as a binary variable yes/no per participant
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Strict Glycemic Control | Participants Who Required Postoperative Blood Transfusion Within 3 Days in the ICU | 0 Participants |
| Standard of Care Control | Participants Who Required Postoperative Blood Transfusion Within 3 Days in the ICU | 0 Participants |