The Role of ImmuKnow® in the Management of Immunosuppressants in the Renal Transplant Patient

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate whether there are any outcome benefits of a serial ImmuKnow assays in the management of de novo renal transplant recipients.

Detailed Description
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Background: The management of renal transplant recipients is challenging in keeping a delicate balance of immunosuppression to avoid either infection (overimmunosuppression), or rejection (under-immunosuppression). Conventional clinical parameters are not adequate enough. ImmuKnow (Cylex Inc, Columbia, MD) is an FDA-cleared assay for the detection of cell mediated immune response in populations undergoing immunosuppressive therapy for organ transplant. There have been limited retrospective studies discussing the effectiveness of the ImmuKnow assay. There is no prospective head-to-head trial showing the benefits of periodic ImmuKnow testing. Objective: To demonstrate whether there are any outcome benefits of a serial ImmuKnow assays in de novo renal transplant recipients Patients and Methods: A prospective, randomized, pilot, controlled 12-month study to compare the outcomes of 2 cohorts of de novo renal transplant patients will be conducted. The outcomes that will be investigated include a combined infection rate (primary end-point), separate infection rates and episodes, acute rejection rate and episodes, quality of life, graft and patient survivals (all secondary end-points). Biopsy of the transplanted kidney is used to confirm rejection whenever possible. Among the study cohort, the patients' immunosuppressants will be adjusted according to the results of a serial ImmuKnow assay besides using conventional clinical parameters; whereas among the control cohort the patients' immunosuppressants will be adjusted according to conventional clinical parameters. Expected Results: At the end of this study we will be able to learn whether the study cohort patients have less infection, less acute rejection, better allograft function, better quality of life, and better graft or patient survivals.

Official Title
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A Randomized, Controlled Trial Evaluating the Role of ImmuKnow® in the Management of Immunosuppressants Regarding Opportunistic Infections and Acute Rejection in the Renal Transplant Patient

Conditions
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Kidney Transplant Immunosuppression

Intervention / Treatment
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* Drug: adjustment of immunosuppressant dosages
* Drug: adjustment of the dosages of immunosuppressants


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: De novo kidney transplant patients who are eligible for kidney transplant according to UNOS criteria and agree to participate in the study. Patients of both sex aged between 18 to 80 years. Exclusion Criteria: Any patient with a known immunocompromised disease (e.g. patients with AIDS) or leukocytosis(>15,000u/L)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: control group<br>Dosages of immunosuppressants will be given according to the results of conventional post-transplant lab | Drug: adjustment of the dosages of immunosuppressants<br>* adjustment of the dosages of immunosuppressants will be done according to the results of conventional post-transplant follow-up lab<br>|
| Experimental: ImmuKnow Study group<br>The dosages of immunosuppressants will be adjusted according to the results of ImmuKnow and conventional post-transplant lab | Drug: adjustment of immunosuppressant dosages<br>* adjustment of immunosuppressant dosages according to the results of ImmuKnow results and routine post-transplant lab results<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the combo-infection rates of the 2 cohorts of renal transplant recipients within the 12-month period after a de novo kidney transplantation | The combo-infection is defined as: If a patient either has new onset culture/or serology/or PCR positive bacterial or viral infections; or moderate neutropenia (absolute netrophile count < 1000/microL) or need GCS-F injection or has fever >38.5 % for longer than 24 hrs then he/she is called to have combo- infection. Percentage of such patients will be compared in Immuknow vs. control group. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event numbers of infection | 1.1 Event numbers of new onset infections;1.2 Episodes of patients with moderate neutropenia (< 1000/microL), 1.3 Episodes of patients needing GCS-F; 1.4. Episodes of fever >38.5 % >= 24 hrs. | 12 months | 
| Percentage of Infection | 2.1 percentages of patients with new onset infections; 2.2 percentages of patients with moderate neutropenia, 2.3 percentages of patients needing GCS-F injection; 2.4 percentages of fever >38.5 >= 24 hrs. | 12 months | 
| Acute rejection | 3.1 Episodes of acute rejection; 3.2 Percentages of Acute Rejection. | 12 months | 
| Life Quality | 4.SF-8 QOL index | 12 months | 
| Allograft function | 5.1 serum creatinine levels 5.2 estimated GFR | 12 months | 
| Graft Survival | 6. Graft survival | 12 months | 
| Patient Survival | 7. Patient survival | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Transplantation, Immunosuppression, Immune monitoring