One-month Latent Tuberculosis Treatment for Renal Transplant Candidates

Study Overview
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Brief Summary
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This is a prospective, single-center, single-arm, open-label study investigating the safety, compliance and pharmacokinetics of 1-month treatment of Isoniazid, Rifapentine and Vitamin B6 in renal transplant candidates.

Detailed Description
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Latent tuberculosis infection (LTBI) or inactive tuberculosis, is a common disease found in patients with end-stage renal disease (ESRD) who are being considered for renal transplant (RT). Approximately 5-15% of patients with LTBI will convert to an active form of TB, especially in patients with a weak immune system. Given the morbidity and mortality associated with active TB disease along with the public health threat, LTBI is routinely treated in pre-transplant candidates. While treatment with isoniazid (INH) for 9 months is the mainstay of therapy, its use poses some clinical challenges due to the prolonged duration of treatment, risk of adverse drug effects, and suboptimal compliance and treatment completion. In addition to these challenges, the consequences of delays in transplant due to the time it takes to complete current treatment options are notable. Most recently, there is a large international, randomized, prospective, phase 3 clinical trial by Swindell et al., that found that 1 month of INH and Rifapentine (1m-INH-RPT) compared to the standard 9-month regimen of INH in HIV patients with LTBI had similar TB incidence in both treatment arms but higher compliance rate and fewer adverse events for patients taking 1m-INH-RPT. Given these findings, if a similar study can be conducted in renal transplant candidate population, it can alleviate the aforementioned challenges being faced in RT candidates. Thus, this is a single-arm, open-label, prospective clinical trial investigating the safety, compliance, pharmacokinetics of 1m-INH-RPT in RT candidates.

Official Title
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One-month Latent Tuberculosis Treatment for Renal Transplant Candidates

Conditions
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Latent Tuberculosis, End Stage Renal Disease, Renal Transplant Candidate for Right Kidney, Renal Transplant Candidate for Left Kidney

Intervention / Treatment
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* Drug: 1 month Rifapentine, Isoniazid and Vitamin B6


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and Women Age > 18 Weight > 30 kg End-stage renal disease Living-related or deceased kidney transplant candidate (not on the waitlist) deemed by their transplant nephrologist Negative serum OR urine pregnancy test Evidence of latent tuberculosis or high risk for tuberculosis: (1) Confirmed positive tuberculin skin test (TST) ≥ 5 mm or positive quantiferon gold test/T-spot and a chest radiograph or chest CT scan without evidence of active pulmonary TB OR (2) Patients with negative TST or quantiferon gold/T-spot test but high risk for tuberculosis are eligible if they have (i) radiographic evidence of previous TB (stable fibronodular changes, including scarring [peribronchial fibrosis, bronchiectasis, and architectural distortion] and nodular opacities in the apical and upper lung zones) and no history of adequate treatment, or (ii) have had close and prolonged contact with a case of active TB. Exclusion Criteria: Age <18 years Absolute neutrophil count of <750 cells/mm3 Hemoglobin < 7.4 g/dL Platelets < 50 x 10E3/uL AST (SGOT) and ALT (SGPT) > 3 times the upper limit of normal (ULN) Total bilirubin > 2.5 times the ULN Presence of active TB Prior history of treatment for active TB or LTBI Known exposure to multidrug-resistant TB Known history of or active porphyria History of liver cirrhosis Evidence of active acute hepatitis Peripheral neuropathy > grade 2 Active drug or alcohol dependence in opinion of investigator that will interfere with adherence On non-modifiable medications with significant drug interactions with Rifapentine or INH On medications known to cause hepatoxicity and/or neutropenia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1 month Rifapentine, Isoniazid and Vitamin B6<br>Participants will receive 28 days of self-administered daily doses of RPT, INH, and pyridoxine (vitamin B6). There are no multiple arms or multiple interventions. All participants will receive all 3 drugs. There are no comparators. | Drug: 1 month Rifapentine, Isoniazid and Vitamin B6<br>* Participants will be treated with one month (4 weeks) of daily Isoniazid, Rifapentine and Vitamin B6.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of adverse events with 1-m INH/RPT/Vit B6 | Treatment discontinuation due to adverse reaction of study drug determined by investigator | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of treatment compliance | Percentage of daily dosage taken within the 28 day course | 28 days | 
| Rate of treatment completion | Completion of 28 day course within a 5 week period | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Latent Tuberculosis, End Stage Renal Disease, Renal Transplant Candidate