Randomized Controlled Trial of ImmuKnow in Liver Transplantation

NCT ID: NCT01764581

Last Updated: 2013-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 206 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2012-03-31

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.

Conditions

Liver Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Tacrolimus regulation according to ImmuKnow values

Intervention Type: PROCEDURE

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

Control

immunosuppressive therapy is managed either by standard practice at our center (Control)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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

Intervention Type: PROCEDURE

Other Intervention Names

Prograf

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Bologna

OTHER

Sponsor Role: lead

Responsible Party

Matteo Ravaioli

PhD, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Antonio Daniele Pinna, MD

Role: STUDY_DIRECTOR

Department of General Surgery and Transplantation; S.Orsola-Malpighi Hospital, University of Bologna

References

Ravaioli M, Neri F, Lazzarotto T, Bertuzzo VR, Di Gioia P, Stacchini G, Morelli MC, Ercolani G, Cescon M, Chiereghin A, Del Gaudio M, Cucchetti A, Pinna AD. Immunosuppression Modifications Based on an Immune Response Assay: Results of a Randomized, Controlled Trial. Transplantation. 2015 Aug;99(8):1625-32. doi: 10.1097/TP.0000000000000650.

Reference Type: DERIVED

PMID: 25757214 (View on PubMed)

Other Identifiers

BolognaCylex01

Identifier Type: -

Identifier Source: org_study_id