Study of Glycemic Control on Liver Transplantation Outcomes

Study Overview
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Brief Summary
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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
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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.

Official Title
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Prospective, Randomized, Open-Label, Controlled Study to Evaluate the Safety and Efficacy of Intensive Glycemic Control on Outcomes Following Liver Transplantation

Conditions
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Evidence of Liver Transplantation, Hyperglycemia, Rejection

Intervention / Treatment
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* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Require Liver Transplantation Age 18 - 80 Able to give informed consent personally or via a family member who has appropriate authorization to do so if patient unconscious. Expected survival following transplantation for > 1 year. Glucose level over 180 mg/dL postoperatively Exclusion Criteria: Inability of patient or family member to give informed consent Not expected to survive for > 1 year following liver transplantation. Previous liver transplantation Acute liver failure Living related donor

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 140 Group<br>Insulin treatment to target blood glucose at 140 mg/dl | Drug: Insulin<br>* Insulin initially as continuous infusion for first 24-48 hours followed by subcutaneous administration once subjects eating and out of intensive care unit.<br>* Other names: Levemir insulin;|
| Active Comparator: 180 Group<br>Insulin treatment to target blood glucose at 180 mg/dl | Drug: Insulin<br>* Insulin initially as continuous infusion for first 24-48 hours followed by subcutaneous administration once subjects eating and out of intensive care unit.<br>* Other names: Levemir insulin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | within 1 year of transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoglycemia | Participants experiencing hypoglycemia (glucose < 70 mg/dL) within the first 3- days following transplantation | Within 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 | Death following liver transplant between 1 day and 1 year | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver, transplantation, Glucose, Hyperglycemia, Insulin, Rejection, Hypoglycemia