One-month Latent Tuberculosis Treatment for Renal Transplant Candidates

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.

Study Overview

• Status: Recruiting
• Conditions: End Stage Renal Disease; Latent Tuberculosis; Renal Transplant Candidate for Right Kidney; Renal Transplant Candidate for Left Kidney
• Intervention / Treatment: Drug: 1 month Rifapentine, Isoniazid and Vitamin B6

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.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Pinki J Bhatt, MD; Phone Number: 7329392610; Email: pb518@rwjms.rutgers.edu

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Pinki J Bhatt
      • Contact: Pinki J Bhatt
      • Principal Investigator: Pinki J Bhatt, MD
      • Principal Investigator: Navaneeth Narayanan, PharmD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1 month Rifapentine, Isoniazid and Vitamin B6; 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; Participants will be treated with one month (4 weeks) of daily Isoniazid, Rifapentine and Vitamin B6.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of reactivation of active tuberculosis	Rate of culture-confirmed tuberculosis disease after completing study regimen	2 years
Trough drug concentration	Isoniazid and Rifapentine serum drug concentration	28 days
3-hour post-dose drug concentration	Isoniazid and Rifapentine serum drug concentration	28 days

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Investigators: Principal Investigator: Pinki Bhatt, MD, Rutgers

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: June 6, 2022
• First Submitted That Met QC Criteria: June 6, 2022
• First Posted (Actual): June 9, 2022

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: End Stage Renal Disease; Latent Tuberculosis; Renal Transplant Candidate
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Urologic Diseases; Disease Attributes; Renal Insufficiency; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Renal Insufficiency, Chronic; Mycobacterium Infections; Latent Infection; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Kidney Failure, Chronic; Tuberculosis; Latent Tuberculosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Anti-Bacterial Agents; Leprostatic Agents; Vitamins; Vitamin B Complex; Antitubercular Agents; Antibiotics, Antitubercular; Fatty Acid Synthesis Inhibitors; Rifapentine; Vitamin B 6; Pyridoxal; Pyridoxine; Isoniazid
• Other Study ID Numbers: Pro2018001735

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No