Isoniazid (INH) Treatment Based on ELISPOT Assay

Study Overview
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Brief Summary
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It has been recommended that all transplant recipients undergo a tuberculin skin test (TST) before transplantation. However, the ability of TST to diagnose latent tuberculosis infection (LTBI) in transplant candidates has been reported to be suboptimal because of high rates of false-negative and false-positive results. The enzyme-linked immunospot assay (ELISPOT) detecting interferon-gamma secreting T-cells for diagnosing tuberculosis infection gave promising results in immunocompromised patients as well as in immunocompetent patients. The investigators will perform a randomized, open-label, prospective trial of isoniazid (INH) prophylaxis based on ELISPOT assay for LTBI in renal transplant recipients.

Detailed Description
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Our previous data have shown that ELISPOT assay was more sensitive to detect LTBI in renal transplant recipients than TST (Kim SH, et al. Transplant Infect Dis 2010 Jan 25 [Epub ahead of print]). However, further studies are eagerly awaited to determine the efficacy of isoniazid (INH) prophylaxis based on ELISPOT assay for LTBI in renal transplant recipients. All adult patients admitted for renal transplantation between May 2010 and April 2013 at the Asan Medical Center, Seoul, South Korea, will be prospectively enrolled. INH (300 mg/day for 9 months) prophylaxis group and no prophylaxis group (control group) will be randomly assigned to all patients with a baseline positive ELISPOT assay regardless of the results of TST. The investigators will compare cumulative probability of developing active TB after transplantation between INH prophylaxis group and control group as primary outcome. Secondary outcomes will be adverse drug reactions, rejection episodes, graft survival, and mortality.

Official Title
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A Prospective, Randomized, Open Labeled Trial of Isoniazid Treatment Based on ELISPOT Assay to Prevent Tuberculosis in a Kidney Transplant Recipient

Conditions
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Kidney Transplant Recipient

Intervention / Treatment
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* Drug: Isoniazid treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 16 years or more Kidney transplant recipients Exclusion Criteria: Patients who do not receive isoniazid treatment due to abnormal liver function (i.e. Child-Pugh Score B or C) Patients who have clinical risk factors for latent tuberculosis infection Close contact with a person with pulmonary TB within the past year Abnormal chest radiography and no prior prophylaxis A history of untreated or inadequately treated TB New infection (i.e. a recent conversion of TST to positive status) If kidney transplant donor has these clinical risk factors for latent tuberculosis infection, the transplant recipient from this donor will be excluded from this study.

Ages Eligible for Study
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Minimum Age: 16 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INH treatment group<br>randomly allocated to INH treatment group in renal transplant recipients with ELISPOT (+) INH 300 mg po qd for 9 months | Drug: Isoniazid treatment<br>* isoniazid 300 mg po qd for 9 months<br>|
| No Intervention: Control group<br>randomly allocated to control group in renal transplant recipients with ELISPOT (+) no treatment | |
| No Intervention: Observation group<br>allocated to observation group in renal transplant recipients with ELISPOT (-) no treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of tuberculosis (the rate of tuberculosis after transplantation) | Confirmed tuberculosis Probable tuberculosis Suspected or possible tuberculosis | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause deaths | TB-associated deaths non-TB-associated deaths | 3 years | 
| INH-associated adverse drug reactions | liver function abnormalities | 3 years | 
| Graft failure |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney, transplantation, tuberculosis, ELISPOT, isoniazid