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One-month Latent Tuberculosis Treatment for Renal Transplant Candidates

Primary Purpose

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

Status

Recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

1 month Rifapentine, Isoniazid and Vitamin B6

About this trial

This is an interventional treatment trial for Latent Tuberculosis focused on measuring Latent Tuberculosis, End Stage Renal Disease, Renal Transplant Candidate

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Pinki J BhattRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

1 month Rifapentine, Isoniazid and Vitamin B6

Arm Description

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.

Outcomes

Primary Outcome Measures

Rate of adverse events with 1-m INH/RPT/Vit B6

Treatment discontinuation due to adverse reaction of study drug determined by investigator

Secondary Outcome Measures

Rate of treatment compliance

Percentage of daily dosage taken within the 28 day course

Rate of treatment completion

Completion of 28 day course within a 5 week period

Full Information

NCT ID

NCT05411744

First Posted

June 6, 2022

Last Updated

April 25, 2023

Sponsor

Rutgers, The State University of New Jersey

1. Study Identification

Unique Protocol Identification Number

NCT05411744

Brief Title

One-month Latent Tuberculosis Treatment for Renal Transplant Candidates

Official Title

One-month Latent Tuberculosis Treatment for Renal Transplant Candidates

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 1, 2022 (Actual)

Primary Completion Date

June 30, 2024 (Anticipated)

Study Completion Date

June 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Rutgers, The State University of New Jersey

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

1 month Rifapentine, Isoniazid and Vitamin B6

Arm Type

Other

Arm Description

Intervention Type

Drug

Intervention Name(s)

1 month Rifapentine, Isoniazid and Vitamin B6

Intervention Description

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

Primary Outcome Measure Information:

Title

Rate of adverse events with 1-m INH/RPT/Vit B6

Description

Treatment discontinuation due to adverse reaction of study drug determined by investigator

Time Frame

28 days

Secondary Outcome Measure Information:

Title

Rate of treatment compliance

Description

Percentage of daily dosage taken within the 28 day course

Time Frame

28 days

Title

Rate of treatment completion

Description

Completion of 28 day course within a 5 week period

Time Frame

28 days

Other Pre-specified Outcome Measures:

Title

Rate of reactivation of active tuberculosis

Description

Rate of culture-confirmed tuberculosis disease after completing study regimen

Time Frame

2 years

Title

Trough drug concentration

Description

Isoniazid and Rifapentine serum drug concentration

Time Frame

28 days

Title

3-hour post-dose drug concentration

Description

Isoniazid and Rifapentine serum drug concentration

Time Frame

28 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Pinki J Bhatt, MD

Phone

7329392610

pb518@rwjms.rutgers.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pinki Bhatt, MD

Organizational Affiliation

Rutgers

Official's Role

Principal Investigator

Facility Information:

Facility Name

Pinki J Bhatt

City

New Brunswick

State/Province

New Jersey

ZIP/Postal Code

08901

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Pinki J Bhatt

First Name & Middle Initial & Last Name & Degree

Pinki J Bhatt, MD

First Name & Middle Initial & Last Name & Degree

Navaneeth Narayanan, PharmD, MPH

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

9827281

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.

Results Reference

background

PubMed Identifier

20070696

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.

Results Reference

background

PubMed Identifier

24590589

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.

Results Reference

background

PubMed Identifier

15783119

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.

Results Reference

background

PubMed Identifier

29660203

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.

Results Reference

background

PubMed Identifier

19075046

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.

Results Reference

background

PubMed Identifier

19729664

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.

Results Reference

background

PubMed Identifier

21789248

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.

Results Reference

background

PubMed Identifier

30865794

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.

Results Reference

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One-month Latent Tuberculosis Treatment for Renal Transplant Candidates

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