Randomized Controlled Trial of ImmuKnow in Liver Transplantation

Study Overview
=================
Brief Summary
-----------------
ImmuKnow detects cell-mediated immunity in solid-organ transplant recipients undergoing immunosuppressive therapy. Increasing ImmuKnow values indicate a decrease of immunosuppression and decreasing ImmuKnow values suggest an increase of immunosuppression. The test measures the amount of ATP produced in CD4+ lymphocytes as a biomarker of lymphocyte activation. This study uses the ImmuKnow assay to proactively adjust immunosuppressive therapy in adult liver transplant recipients to reduce the risk of adverse events

Detailed Description
-----------------
We performed a randomized prospective interventional trial where the Interventional group had immunosuppression modified according to ImmuKnow values. Immunosuppression was decreased by 25% if ImmuKnow values were less than 130 ng/mL ATP. Similarly, immunosuppression was increased by 25% if ImmuKnow values were greater than 450 ng/mL ATP. Immunosuppression of the Control group was managed by the Standard of Care at our institution. ImmuKnow was performed before liver transplant, after surgery and at each clinic visit with the approximate schedule: day 1; weekly, weeks 1-4; week 6; week 8; monthly, months 3-6; and months 9 and 12. ImmuKnow testing was repeated within 7 days of a suspected/confirmed rejection or infection and again within 1 week of resolution.

Official Title
-----------------
Randomized Controlled Interventional Trial of Immunosuppression Modification Based on the Cylex™ ImmuKnow® Assay in Adult Liver Transplant Recipients

Conditions
-----------------
Liver Disease

Intervention / Treatment
-----------------
* Procedure: Tacrolimus regulation according to ImmuKnow values


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: consecutive adult liver transplant recipients at our center; patients not entered into other studies; provided consent. Exclusion Criteria: available follow-up; consent removed.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tacrolimus dose regulation<br>Tacrolimus dose was reduced by 25% when ImmuKnow values were below 130 ng/mL ATP and increased by 25% when ImmuKnow values exceeded 450 ng/mL. | Procedure: Tacrolimus regulation according to ImmuKnow values<br>* Tacrolimus dose was reduced by 25% when ImmuKnow values were below 130 ng/mL ATP and increased by 25% when ImmuKnow values exceeded 450 ng/mL. Further reductions or increases were made after serial measures until ImmuKnow values stabilized between 130 and 450 ng/mL ATP. The values of 130 and 450 ng/mL ATP were previously documented as thresholds for risks of infection and rejection, respectively with a value of 280 ng/mL corresponding with the greatest negative predictive value for either event<br>* Other names: Prograf;|
| No Intervention: Control<br>immunosuppressive therapy is managed either by standard practice at our center (Control) | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of adverse events | Comparison of adverse events consisting of allograft rejection, severe infections, graft loss and death between the Control and Interventional groups | 12 months posttransplant | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
immune monitoring, immune cell function ImmuKnow, randomized controlled trial, immunosuppression management, infection, rejection, liver transplantation, Cylex