1-Month TB Therapy for Kidney Transplant Candidates

Overseen by Pinki Bhatt, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Hepatotoxic drugs, Neutropenia drugs

Disqualifiers: Active TB, Liver cirrhosis, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests a treatment with two antibiotics and a vitamin for kidney transplant candidates who have latent TB. The goal is to see if this shorter treatment is safe, effective, and easier for patients to complete compared to the longer standard treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot participate if you are on medications that have significant interactions with Rifapentine or Isoniazid, or if they cause liver damage or low white blood cell counts.

Is the 1-month TB therapy safe for kidney transplant candidates?

The safety of isoniazid (INH) and rifapentine, used in TB therapy, has been studied in patients with kidney issues. Some patients on hemodialysis experienced neurotoxic side effects, like encephalopathy (brain dysfunction) and cerebellar syndrome (coordination problems), especially when pyridoxine (Vitamin B6) supplements were low. Increasing pyridoxine helped resolve these issues, suggesting that careful monitoring and supplementation can improve safety. ^{1 2 3 4 5}

What makes the 1-Month TB Therapy for Kidney Transplant Candidates unique?

This treatment is unique because it combines isoniazid and rifapentine with vitamin B6 to prevent neurotoxic side effects, which is particularly important for patients with kidney issues who are more sensitive to these effects. ^{1 2 3 6 7}

Research Team

Pinki Bhatt, MD

Principal Investigator

Rutgers

Eligibility Criteria

This trial is for adults over 18 with end-stage kidney disease who are candidates for a kidney transplant, weigh more than 30 kg, and have latent tuberculosis or a high risk of developing it. They must not be on the waitlist yet but approved by their nephrologist. Pregnant women and individuals with certain medical conditions or drug dependencies that could affect treatment adherence are excluded.

Inclusion Criteria

You are someone who is waiting for a kidney transplant or have been considered for a transplant by a kidney doctor.

I weigh more than 30 kilograms.

I am older than 18 years.

Exclusion Criteria

You have signs of a recent hepatitis infection.

I have been treated for TB in the past.

I have a history of or currently have porphyria.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 28 days of self-administered daily doses of Rifapentine, Isoniazid, and Vitamin B6

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Isoniazid (Antibiotic)
• Rifapentine (Antibiotic)
• Vitamin B6 (Other)

Trial Overview The study tests a one-month regimen combining Rifapentine, Isoniazid, and Vitamin B6 in renal transplant candidates to assess safety, compliance, and how the body processes these drugs. It's an open-label study where all participants receive the same treatment without any comparison group.

Participant Groups

Group I: 1 month Rifapentine, Isoniazid and Vitamin B6 Experimental Treatment 1 Intervention

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.

Isoniazid is already approved in Canada, Japan, China, Switzerland for the following indications:

Approved in Canada as Isoniazid for:

• Tuberculosis

Approved in Japan as Isoniazid for:

• Tuberculosis

Approved in China as Isoniazid for:

• Tuberculosis

Approved in Switzerland as Isoniazid for:

• Tuberculosis

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Dr. Jonathan Holloway

Rutgers, The State University of New Jersey

Chief Executive Officer since 2020

PhD in History from Yale University

Dr. Brian Strom

Rutgers, The State University of New Jersey

Chief Medical Officer since 2014

MD from Rutgers New Jersey Medical School

Findings from Research

Isoniazid (INH) can cause encephalopathy in patients on hemodialysis, as seen in two cases involving patients with tuberculosis, highlighting the need for careful monitoring of this medication in vulnerable populations.

After stopping INH and increasing pyridoxine dosage, both patients recovered their consciousness within a week, suggesting that prompt recognition and management of INH-induced encephalopathy can lead to positive outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Encephalopathy secondary to isoniazid in patients on hemodialysis. Abbas, MT., Khan, FY., Sulimon, S., et al.[2021]

A hemodialysis patient treated for tuberculosis with isoniazid, rifampin, and pyrazinamide developed acute cerebellar dysfunction, which was linked to isoniazid use.

The symptoms resolved quickly after stopping isoniazid and pyrazinamide, lowering the isoniazid dose, and adding pyridoxine, suggesting that patients with renal failure on isoniazid should receive pyridoxine to prevent neurotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebellar syndrome caused by isoniazid. Blumberg, EA., Gil, RA.[2019]

Patients with end-stage renal disease receiving isoniazid therapy are at a higher risk of neurotoxic side effects, particularly if they are taking less than 100 mg/day of pyridoxine supplements.

To prevent neurotoxicity from isoniazid in hemodialysis patients, it is recommended to supplement with at least 100 mg/day of pyridoxine, as these patients have altered metabolism leading to low levels of the active form, pyridoxal phosphate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isoniazid-induced neurotoxicity in chronic dialysis patients: report of three cases and a review of the literature. Siskind, MS., Thienemann, D., Kirlin, L.[2022]

In a study of 38 children receiving isoniazid therapy for 2 to 18 months, 13% were found to be deficient in pyridoxine (vitamin B6), despite not showing clinical symptoms of deficiency.

Children taking higher doses of isoniazid (over 10 mg/kg/day) had a greater risk of pyridoxine deficiency, suggesting that current guidelines on vitamin B6 supplementation during isoniazid therapy may need to be revised, especially for those with poor nutritional status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyridoxine deficiency in children treated with isoniazid. Pellock, JM., Howell, J., Kendig, EL., et al.[2019]

This study is the first to evaluate the safety and tolerability of a once-weekly treatment of rifapentine plus isoniazid (3HP) for 3 months in hemodialysis patients, achieving a completion rate of 65.4%.

While the treatment did not cause hepatotoxicity, it was associated with a high rate of adverse events, occurring in 69.2% of participants, indicating that while 3HP is safe in terms of liver function, it may lead to other side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three months of rifapentine and isoniazid for latent tuberculosis infection in hemodialysis patients: High rates of adverse events. Lin, SY., Chiu, YW., Lu, PL., et al.[2019]

Pyridoxal can completely protect Mycobacterium tuberculosis from the effects of isoniazid, a common antibiotic used to treat tuberculosis, when present in a synthetic liquid medium at a concentration of 10 µg/ml.

The protective effect of pyridoxal is linked to its ability to inhibit the uptake of isoniazid by the bacteria, which is influenced by the presence of specific nutrients in the medium, suggesting that the interaction between pyridoxal, isoniazid, and certain medium components reduces the drug's availability to the bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanism for the pyridoxal neutralization of isoniazid action of Mycobacterium tuberculosis. Beggs, WH., Jenne, JW.[2021]

Pyridoxine significantly decreases the intestinal absorption of isoniazid, with a reduction in apparent permeability and absorption rate by approximately 43.7% and 36.4%, respectively, when co-administered.

Despite the inhibition of isoniazid absorption by pyridoxine, the overall pharmacokinetics of isoniazid, including its blood concentration levels, were not significantly affected, likely due to isoniazid's rapid absorption phase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of pyridoxine on the intestinal absorption and pharmacokinetics of isoniazid in rats. Zhou, Y., Jiao, Y., Wei, YH., et al.[2021]

References

1. India pubmed.ncbi.nlm.nih.gov

Encephalopathy secondary to isoniazid in patients on hemodialysis. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Cerebellar syndrome caused by isoniazid. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Isoniazid-induced neurotoxicity in chronic dialysis patients: report of three cases and a review of the literature. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Pyridoxine deficiency in children treated with isoniazid. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Three months of rifapentine and isoniazid for latent tuberculosis infection in hemodialysis patients: High rates of adverse events. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Mechanism for the pyridoxal neutralization of isoniazid action of Mycobacterium tuberculosis. [2021]

7. France pubmed.ncbi.nlm.nih.gov

Effects of pyridoxine on the intestinal absorption and pharmacokinetics of isoniazid in rats. [2021]