Randomized Controlled Trial of ImmuKnow in Liver Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01764581
Recruitment Status : Completed
First Posted : January 9, 2013
Last Update Posted : January 9, 2013
Information provided by (Responsible Party):
Matteo Ravaioli, University of Bologna

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

Condition or disease Intervention/treatment Phase
Liver Disease Procedure: Tacrolimus regulation according to ImmuKnow values Not Applicable

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 206 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Controlled Interventional Trial of Immunosuppression Modification Based on the Cylex™ ImmuKnow® Assay in Adult Liver Transplant Recipients
Study Start Date : July 2008
Actual Primary Completion Date : October 2010
Actual Study Completion Date : March 2012

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Tacrolimus dose regulation
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
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
Other Name: Prograf
No Intervention: Control
immunosuppressive therapy is managed either by standard practice at our center (Control)

Primary Outcome Measures :
  1. Comparison of adverse events [ Time Frame: 12 months posttransplant ]
    Comparison of adverse events consisting of allograft rejection, severe infections, graft loss and death between the Control and Interventional groups

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01764581

Sponsors and Collaborators
University of Bologna
Study Director: Antonio Daniele Pinna, MD Department of General Surgery and Transplantation; S.Orsola-Malpighi Hospital, University of Bologna

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Matteo Ravaioli, PhD, MD, University of Bologna Identifier: NCT01764581     History of Changes
Other Study ID Numbers: BolognaCylex01
First Posted: January 9, 2013    Key Record Dates
Last Update Posted: January 9, 2013
Last Verified: October 2010

Keywords provided by Matteo Ravaioli, University of Bologna:
immune monitoring
immune cell function ImmuKnow
randomized controlled trial
immunosuppression management
liver transplantation

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action