1-Month TB Therapy for Kidney Transplant Candidates

Overseen By Pinki J Bhatt, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a 1-month medication regimen for individuals preparing for a kidney transplant. The treatment includes three drugs: Isoniazid (an antibiotic), Rifapentine (an antibiotic), and Vitamin B6, which help prevent tuberculosis, a serious lung infection. It targets those with end-stage kidney disease who are at risk for tuberculosis. Participants should not have active TB and must be awaiting a kidney transplant. As a Phase 4 trial, this research involves an FDA-approved treatment to better understand its benefits for more patients.

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.

What is the safety track record for Isoniazid, Rifapentine, and Vitamin B6?

Research has shown that the combination of Isoniazid, Rifapentine, and Vitamin B6 is generally well-tolerated by patients. In past studies, participants often completed their treatment with fewer liver-related issues, a common side effect. Specifically, one study found that none of the patients developed tuberculosis after the treatment, supporting its safety and effectiveness. This combination has successfully treated latent tuberculosis in similar patient groups, indicating it is a safe choice for preventing tuberculosis in individuals who have had kidney transplants. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this treatment because it offers a potentially faster and simpler option for preventing tuberculosis (TB) in kidney transplant candidates. Unlike traditional TB prevention regimens, which often require several months of therapy, this treatment combines rifapentine, isoniazid, and vitamin B6 into a one-month course. This shorter duration could improve patient adherence and reduce the risk of side effects associated with prolonged medication use. Additionally, the inclusion of vitamin B6 helps mitigate the risk of nerve damage, a common concern with isoniazid. Overall, this approach could make TB prevention more manageable for patients awaiting kidney transplants.

What evidence suggests that this treatment might be an effective treatment for kidney transplant candidates?

Research has shown that using Rifapentine and Isoniazid together effectively treats latent tuberculosis infection (LTBI). Studies have found that this treatment works faster and is as successful as other methods. People taking this combination are more likely to complete their treatment and experience fewer liver problems compared to other TB treatments. Vitamin B6 is added to prevent nerve damage, a potential side effect of Isoniazid. This treatment is also safe for individuals awaiting a kidney transplant, helping them manage LTBI before surgery. All participants in this trial will receive a combination of Rifapentine, Isoniazid, and Vitamin B6 for 28 days. ^{3 5 6 7 8}

Who Is on the Research Team?

Pinki Bhatt, MD

Principal Investigator

Rutgers

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Isoniazid
• Rifapentine
• Vitamin B6

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.

How Is the Trial Designed?

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 United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as Isoniazid for:

• Tuberculosis

Approved in European Union as Isoniazid for:

• Tuberculosis

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28276008/

Three months of weekly rifapentine plus isoniazid for latent ... Results: Eleven patients were men, and the median age was 60 years (range 44-72). Eight patients were liver, and four kidney transplant candidates. The ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27548035/

Twelve-Week Rifapentine Plus Isoniazid Versus 9-Month ... Twelve-week RPT/INH appears to be an excellent choice for LTBI in RTC. It has a higher treatment completion rate and causes less transaminase elevations.

3. researchgate.net researchgate.net/publication/314507105_Three_months_of_weekly_rifapentine_plus_isoniazid_for_latent_tuberculosis_treatment_in_solid_organ_transplant_candidates

Three months of weekly rifapentine plus isoniazid for latent ... The combination of rifapentine and isoniazid administered weekly for 3 months (3HP) has been approved as a first-line treatment of latent TB ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11317863/

Tuberculosis in kidney transplant candidates and recipients Fluoroquinolone-based nonrifamycin ATT has shown excellent results in transplant recipients. The review incorporates the latest guidelines and gives an overview ...

5. diva-portal.org diva-portal.org/smash/get/diva2:1543534/FULLTEXT01.pdf

Treating latent tuberculosis A newer treatment regimen is the rifapentine plus isoniazid combination therapy. It is an effective regimen against LTBI and has a shorter treatment duration.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24142036/

Short-course isoniazid plus rifapentine directly observed ... No cases of TB developed during 20.4 months after transplant among INH/RPT-treated recipients. Conclusions: For carefully selected SOT ...

7. trial.medpath.com trial.medpath.com/clinical-trial/e54d085c1548da34/nct03900858-short-course-rifapentine-isoniazid-tuberculosis

Short Course Rifapentine and Isoniazid for the Preventive ... And the treatment completion rate is higher. The investigators' previous study showed a 3-month weekly rifapentine and isoniazid regimen had a high protective ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02651259?cond=%22Tuberculosis%22&intr=%22Rifamycin%22&viewType=Table&rank=4&tab=results

Study Results | Evaluating PK, Tolerability, and Safety of ... Participants received 12 directly observed once-weekly doses of RPT, INH, and pyridoxine (vitamin B6) at study entry and at 11 weekly follow-up visits.