Clinical trial NCT05411744: One-month Latent Tuberculosis Treatment for Renal Transplant Candidates
Official title: One-month Latent Tuberculosis Treatment for Renal Transplant Candidates
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Latent Tuberculosis
End Stage Renal Disease
Renal Transplant Candidate for Right Kidney
Renal Transplant Candidate for Left Kidney
Keywords: Latent Tuberculosis
End Stage Renal Disease
Renal Transplant Candidate
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
First posted: 2022-06-09
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of adverse events with 1-m INH/RPT/Vit B6
timeFrame: 28 days
Secondary outcomes:
measure: Rate of treatment compliance
timeFrame: 28 days
measure: Rate of treatment completion
timeFrame: 28 days
Other outcomes:
measure: Rate of reactivation of active tuberculosis
timeFrame: 2 years
measure: Trough drug concentration
timeFrame: 28 days
measure: 3-hour post-dose drug concentration
timeFrame: 28 days
Locations:
city: New Brunswick
country: United States
facility: Pinki J Bhatt
state: New Jersey
Study officials:
affiliation: Rutgers
name: Pinki Bhatt, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Singh N, Paterson DL. Mycobacterium tuberculosis infection in solid-organ transplant recipients: impact and implications for management. Clin Infect Dis. 1998 Nov;27(5):1266-77. doi: 10.1086/514993.
citation: Subramanian A, Dorman S; AST Infectious Diseases Community of Practice. Mycobacterium tuberculosis in solid organ transplant recipients. Am J Transplant. 2009 Dec;9 Suppl 4:S57-62. doi: 10.1111/j.1600-6143.2009.02894.x. No abstract available.
citation: Adamu B, Abdu A, Abba AA, Borodo MM, Tleyjeh IM. Antibiotic prophylaxis for preventing post solid organ transplant tuberculosis. Cochrane Database Syst Rev. 2014 Mar 4;2014(3):CD008597. doi: 10.1002/14651858.CD008597.pub2.
citation: Agarwal SK, Gupta S, Dash SC, Bhowmik D, Tiwari SC. Prospective randomised trial of isoniazid prophylaxis in renal transplant recipient. Int Urol Nephrol. 2004;36(3):425-31. doi: 10.1007/s11255-004-6251-6.
citation: Rafiei N, Williams J, Mulley WR, Trauer JM, Jenkin GA, Rogers BA. Mycobacterium tuberculosis: Active disease and latent infection in a renal transplant cohort. Nephrology (Carlton). 2019 May;24(5):569-574. doi: 10.1111/nep.13386.
citation: van den Boogaard J, Kibiki GS, Kisanga ER, Boeree MJ, Aarnoutse RE. New drugs against tuberculosis: problems, progress, and evaluation of agents in clinical development. Antimicrob Agents Chemother. 2009 Mar;53(3):849-62. doi: 10.1128/AAC.00749-08. Epub 2008 Dec 15. No abstract available.
citation: Zhang T, Zhang M, Rosenthal IM, Grosset JH, Nuermberger EL. Short-course therapy with daily rifapentine in a murine model of latent tuberculosis infection. Am J Respir Crit Care Med. 2009 Dec 1;180(11):1151-7. doi: 10.1164/rccm.200905-0795OC. Epub 2009 Sep 3.
citation: Holland DP, Sanders GD, Hamilton CD, Stout JE. Potential economic viability of two proposed rifapentine-based regimens for treatment of latent tuberculosis infection. PLoS One. 2011;6(7):e22276. doi: 10.1371/journal.pone.0022276. Epub 2011 Jul 18.
citation: Swindells S, Ramchandani R, Gupta A, Benson CA, Leon-Cruz J, Mwelase N, Jean Juste MA, Lama JR, Valencia J, Omoz-Oarhe A, Supparatpinyo K, Masheto G, Mohapi L, da Silva Escada RO, Mawlana S, Banda P, Severe P, Hakim J, Kanyama C, Langat D, Moran L, Andersen J, Fletcher CV, Nuermberger E, Chaisson RE; BRIEF TB/A5279 Study Team. One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis. N Engl J Med. 2019 Mar 14;380(11):1001-1011. doi: 10.1056/NEJMoa1806808.