Study of Glycemic Control on Liver Transplantation Outcomes

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

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.

Study Overview

• Status: Completed
• Conditions: Hyperglycemia; Rejection; Evidence of Liver Transplantation
• Intervention / Treatment: Drug: Insulin

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.

• Study Type: Interventional
• Enrollment (Actual): 164
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Northwestern University
• Investigators: Principal Investigator: Mark E Molitch, M.D., Northwestern University Feinberg School of Medicine

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: September 28, 2010
• First Submitted That Met QC Criteria: September 28, 2010
• First Posted (Estimate): September 29, 2010

Study Record Updates

• Last Update Posted (Estimate): December 23, 2016
• Last Update Submitted That Met QC Criteria: October 31, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Insulin; Hypoglycemia; Rejection; Hyperglycemia; transplantation; Glucose; Liver
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: STU00005806

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO