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

Kidney Transplant Immunosuppression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01424345
• Other study ID #: 1997050
• Status: Terminated
• Phase: Phase 4
• First received: August 24, 2011
• Last updated: October 4, 2012
• Start date: December 2011
• Est. completion date: July 2012

Study information

• Verified date: October 2012
• Source: CAMC Health System
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. De novo kidney transplant patients who are eligible for kidney transplant according to UNOS criteria and agree to participate in the study.

2. 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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Kidney Transplant Immunosuppression

Intervention

Drug:
• adjustment of immunosuppressant dosages
adjustment of immunosuppressant dosages according to the results of ImmuKnow results and routine post-transplant lab results
• adjustment of the dosages of immunosuppressants
adjustment of the dosages of immunosuppressants will be done according to the results of conventional post-transplant follow-up lab

Locations

Country	Name	City	State
United States	CAMC	Charleston	West Virginia

Sponsors (1)

Lead Sponsor	Collaborator
CAMC Health System

Country where clinical trial is conducted

United States, 

References & Publications (11)

1. ImmuKnow®® Cylex™ Immune Cell Function Assay, Package Insert (http://www.cylex.net/pdf/ImmuKnow_Insert-cx.pdf)

Batal I, Zeevi A, Heider A, Girnita A, Basu A, Tan H, Shapiro R, Randhawa P. Measurements of global cell-mediated immunity in renal transplant recipients with BK virus reactivation. Am J Clin Pathol. 2008 Apr;129(4):587-91. doi: 10.1309/23YGPB1E758ECCFP. — View Citation

Gautam A, Fischer SA, Yango AF, Gohh RY, Morrissey PE, Monaco AP. Cell mediated immunity (CMI) and post transplant viral infections--role of a functional immune assay to titrate immunosuppression. Int Immunopharmacol. 2006 Dec 20;6(13-14):2023-6. Epub 2006 Oct 24. — View Citation

Huskey J, Gralla J, Wiseman AC. Single time point immune function assay (ImmuKnow) testing does not aid in the prediction of future opportunistic infections or acute rejection. Clin J Am Soc Nephrol. 2011 Feb;6(2):423-9. doi: 10.2215/CJN.04210510. Epub 2010 Nov 18. — View Citation

John Ware, Jr, Ph.D., Mark Kosinski, M.A., James E. Dewey, Ph.D., Barbara Gandek, M.S. How to score & interpret single item health status measures. Manual for users of SF8, Lincdn, RI. Quality Metric Incorporated, 2001. 1998-2001

Knight RJ, Kerman RH, McKissick E, Lawless A, Podder H, Katz S, Van Buren CT, Kahan BD. Selective corticosteroid and calcineurin-inhibitor withdrawal after pancreas-kidney transplantation utilizing thymoglobulin induction and sirolimus maintenance therapy. Clin Transplant. 2008 Sep-Oct;22(5):645-50. doi: 10.1111/j.1399-0012.2008.00839.x. Epub 2008 Jul 24. — View Citation

Kobashigawa JA, Kiyosaki KK, Patel JK, Kittleson MM, Kubak BM, Davis SN, Kawano MA, Ardehali AA. Benefit of immune monitoring in heart transplant patients using ATP production in activated lymphocytes. J Heart Lung Transplant. 2010 May;29(5):504-8. doi: 10.1016/j.healun.2009.12.015. Epub 2010 Feb 4. — View Citation

Kowalski R, Post D, Schneider MC, Britz J, Thomas J, Deierhoi M, Lobashevsky A, Redfield R, Schweitzer E, Heredia A, Reardon E, Davis C, Bentlejewski C, Fung J, Shapiro R, Zeevi A. Immune cell function testing: an adjunct to therapeutic drug monitoring in transplant patient management. Clin Transplant. 2003 Apr;17(2):77-88. — View Citation

Kowalski RJ, Post DR, Mannon RB, Sebastian A, Wright HI, Sigle G, Burdick J, Elmagd KA, Zeevi A, Lopez-Cepero M, Daller JA, Gritsch HA, Reed EF, Jonsson J, Hawkins D, Britz JA. Assessing relative risks of infection and rejection: a meta-analysis using an immune function assay. Transplantation. 2006 Sep 15;82(5):663-8. — View Citation

Reinsmoen NL, Cornett KM, Kloehn R, Burnette AD, McHugh L, Flewellen BK, Matas A, Savik K. Pretransplant donor-specific and non-specific immune parameters associated with early acute rejection. Transplantation. 2008 Feb 15;85(3):462-70. doi: 10.1097/TP.0b013e3181612ead. — View Citation

Sánchez-Velasco P, Rodrigo E, Valero R, Ruiz JC, Fernández-Fresnedo G, López-Hoyos M, Piñera C, Palomar R, Leyva-Cobián F, Arias M. Intracellular ATP concentrations of CD4 cells in kidney transplant patients with and without infection. Clin Transplant. 2008 Jan-Feb;22(1):55-60. doi: 10.1111/j.1399-0012.2007.00744.x. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	Acute rejection	3.1 Episodes of acute rejection; 3.2 Percentages of Acute Rejection.	12 months	Yes
Secondary	Life Quality	4.SF-8 QOL index	12 months	No
Secondary	Allograft function	5.1 serum creatinine levels 5.2 estimated GFR	12 months	No
Secondary	Graft Survival	6. Graft survival	12 months	Yes
Secondary	Patient Survival	7. Patient survival	12 months	Yes