Clinical trial NCT00780026: Intraoperative Glucose Control in Liver Transplant
Official title: Effect Of Intraoperative Strict Glycemic Control During Liver Transplantation On Postoperative Morbidity And Mortality
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Liver Transplant
Keywords: liver
transplant
blood sugar
Lead sponsor: University of Michigan
Sponsor class: OTHER
First posted: 2008-10-24
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Infection Rates
timeFrame: 30 days
measure: Number of Participants With One Year Survival Post Transplant
timeFrame: 12 months
Secondary outcomes:
measure: Hospital Length of Stay
timeFrame: 12 months
measure: Participants Who Required Postoperative Blood Transfusion Within 3 Days in the ICU
timeFrame: 12 months
measure: Number of Participants With a Need for Hemodialysis
timeFrame: 12 months post surgery
measure: Number of Participants With Biliary Complications
timeFrame: 12 months
measure: Number of Participants With Venous Thrombotic Complications
timeFrame: 12 months
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: Universitry of Michigan
name: Shawn Pelletier, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kumar SS, Pelletier SJ, Shanks A, Thompson A, Sonnenday CJ, Picton P. Intraoperative glycemic control in patients undergoing Orthotopic liver transplant: a single center prospective randomized study. BMC Anesthesiol. 2020 Jan 4;20(1):3. doi: 10.1186/s12871-019-0918-0.