Isoniazid (INH) Treatment Based on ELISPOT Assay

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

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.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant Recipient
• Intervention / Treatment: Drug: Isoniazid treatment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 831
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

  1. Close contact with a person with pulmonary TB within the past year
  2. Abnormal chest radiography and no prior prophylaxis
  3. A history of untreated or inadequately treated TB

  4. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: INH treatment group; randomly allocated to INH treatment group in renal transplant recipients with ELISPOT (+); INH 300 mg po qd for 9 months	Drug: Isoniazid treatment; isoniazid 300 mg po qd for 9 months
NO_INTERVENTION: Control group; randomly allocated to control group in renal transplant recipients with ELISPOT (+); no treatment
NO_INTERVENTION: Observation group; allocated to observation group in renal transplant recipients with ELISPOT (-); no treatment

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Asan Medical Center

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (ACTUAL): May 1, 2013
• Study Completion (ACTUAL): November 1, 2013

Study Registration Dates

• First Submitted: March 11, 2010
• First Submitted That Met QC Criteria: March 15, 2010
• First Posted (ESTIMATE): March 16, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): December 12, 2013
• Last Update Submitted That Met QC Criteria: December 11, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: transplantation; kidney; tuberculosis; ELISPOT; isoniazid
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Anti-Bacterial Agents; Antitubercular Agents; Fatty Acid Synthesis Inhibitors; Isoniazid
• Other Study ID Numbers: 2010-0009