One-month Latent Tuberculosis Treatment for Renal Transplant Candidates

Sponsor

Rutgers, The State University of New Jersey (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05411744

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Latent Tuberculosis End Stage Renal Disease Renal Transplant Candidate for Right Kidney Renal Transplant Candidate for Left Kidney	Drug: Rifapentine	Phase 4

Detailed Description

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 our renal transplant candidate population, it can alleviate the aforementioned challenges being faced in our 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

One-month Latent Tuberculosis Treatment for Renal Transplant Candidates

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Jun 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 month Rifapentine, Isoniazid and Vitamin B6 Participants will receive 28 days of self-administered daily doses of RPT, INH, and pyridoxine (vitamin B6)	Drug: Rifapentine Participants will be treated with one month (4 weeks) of daily Isoniazid, Rifapentine and Vitamin B6. Other Names: Isoniazid Vitamin B6

Arm

Intervention/Treatment

Experimental: 1 month Rifapentine, Isoniazid and Vitamin B6

Participants will receive 28 days of self-administered daily doses of RPT, INH, and pyridoxine (vitamin B6)

Drug: Rifapentine

Participants will be treated with one month (4 weeks) of daily Isoniazid, Rifapentine and Vitamin B6.

Other Names:

Isoniazid

Vitamin B6

Outcome Measures

Primary Outcome Measures

Rate of adverse events with 1-m INH/RPT/Vit B6 [28 days]
Treatment discontinuation due to adverse reaction of study drug determined by investigator

Secondary Outcome Measures

Rate of treatment compliance [28 days]
Percentage of daily dosage taken within the 28 day course
Rate of treatment completion [28 days]
Completion of 28 day course within a 5 week period

Other Outcome Measures

Rate of reactivation of active tuberculosis [2 years]
Rate of culture-confirmed tuberculosis disease after completing study regimen
Pharmacokinetic parameters [28 days]
Serum drug concentration level

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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