Evaluation of Rifamycin-Based Regimens: Isoniazid Plus Rifapentine, Rifampicin, and Isoniazid Plus Rifampicin for Latent Tuberculosis in End-Stage Kidney Disease

The primary objective of this study is to evaluate the **treatment completion** rates of three short-course rifamycin-based regimens for the management of latent tuberculosis infection in patients with end-stage kidney disease. Specifically, the study aims to determine if treatment completion with three months of once-weekly isoniazid plus rifapentine (3HP) or four months of daily rifampicin (4R) is superior compared to three months of daily isoniazid plus rifampicin (3HR). This is clinically relevant as optimizing treatment regimens can improve adherence and outcomes in this vulnerable patient population.

Secondary objectives include assessing the safety and tolerability of the 3HR, 3HP, and 4R regimens in the same patient cohort. Understanding the safety profile is crucial for minimizing adverse effects and ensuring patient safety during treatment.

The clinical trial focuses on patients with **latent tuberculosis infection** in the context of end-stage kidney disease. The study population includes both male and female participants aged 18 years and older, specifically those with kidney disease at stage 4 or higher, characterized by a glomerular filtration rate of 29 mL/minute or lower, or those under substitutive renal therapy. The trial does not target a vulnerable population. Participants were selected based on their need for treatment of latent tuberculosis infection, with additional criteria including a negative pregnancy test for females and a commitment to using appropriate barrier contraceptive measures. The sponsor has not provided information regarding the total number of participants in the trial. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of three short-course rifamycin-based regimens for the treatment of **latent tuberculosis infection** in patients with end-stage kidney disease. This randomized, controlled trial will compare three months of daily isoniazid plus rifampicin (3HR), three months of once-weekly isoniazid plus rifapentine (3HP), and four months of daily rifampicin (4R). The primary objective is to determine if treatment completion rates are higher with the 3HP or 4R regimens compared to the 3HR regimen. The trial is expected to run from October 2023 to April 2026, with participant involvement lasting up to 20 weeks depending on the assigned treatment arm.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, kidney disease stage, and a negative pregnancy test for females. Following randomization, participants will attend regular follow-up visits to monitor treatment adherence, assess for adverse events, and ensure compliance with the dosing schedule. The end-of-study visit will evaluate the completion of the treatment regimen and collect final data on safety and efficacy outcomes.

The trial employs a double-blind design to minimize bias, with neither participants nor investigators aware of the specific treatment allocation. Participants are expected to adhere to the assigned regimen without interruptions longer than specified durations, as outlined in the primary endpoints. Conditions that may lead to early termination from the study include significant adverse events or non-compliance with the treatment protocol. The trial aims to provide valuable insights into the optimal management of latent tuberculosis infection in this vulnerable patient population.

The clinical trial involves the administration of **Cemidón 300 B6**, a pharmaceutical product in the form of a tablet, containing the active substances **isoniazid** and **pyridoxine**. This medication is administered orally with a maximum daily dose of 300 mg and a total dose of up to 900 mg over a treatment period of 12 weeks. The product is manufactured by CHIESI ESPAÑA S.A.U. and is classified under the ATC code J04AC51, indicating its use in combinations of isoniazid. The trial aims to evaluate the efficacy of this regimen in treating latent tuberculosis infection in patients with end-stage kidney disease.

**Rifaldin 300 mg cápsulas** is another investigational product used in the trial, presented as a hard capsule containing **rifampicin** as the active ingredient. This medication is also administered orally, with a maximum daily dose of 600 mg and a total dose of 600 mg over a 16-week treatment period. Manufactured by MARION MERRELL S.A., Rifaldin is categorized under the ATC code J04AB02, which pertains to rifampicin. The trial assesses its effectiveness as part of a four-month daily regimen for latent tuberculosis infection.

Additionally, the trial includes **Rimactán 300 mg cápsulas duras**, another hard capsule formulation containing **rifampicin**. This product is administered orally with a maximum daily dose of 600 mg and a total dose of 600 mg over a 12-week treatment period. Produced by SANDOZ FARMACÉUTICA, S.A., Rimactán shares the same ATC classification as Rifaldin, J04AB02. The trial evaluates its role in a three-month daily regimen for the treatment of latent tuberculosis infection.

The trial also investigates the use of **RIFAPENTINE**, a film-coated tablet containing the active substance **rifapentine**. This medication is administered orally, with a total dose of 900 mg over a 12-week treatment period, although no specific daily dose is indicated. RIFAPENTINE is designated as an orphan drug for the treatment of latent tuberculosis infection, and its efficacy is compared in a three-month once-weekly regimen. The trial aims to determine the completion rates and effectiveness of this regimen in patients with end-stage kidney disease.

Efficacy in this clinical trial will be assessed primarily by evaluating the **treatment completion rates** among participants with latent tuberculosis infection and end-stage kidney disease. The primary endpoint is defined by the proportion of participants who successfully complete their assigned treatment regimen. This includes three different regimens: three months of daily isoniazid plus rifampicin (3HR), three months of once-weekly isoniazid plus rifapentine (3HP), and four months of daily rifampicin (4R). For the 3HR arm, completion is defined as 90 doses within a maximum of 16 weeks, with no interruptions longer than two weeks on more than two occasions. For the 3HP arm, completion is defined as 12 doses within a maximum of 14 weeks, with no interruptions longer than 10 days. For the 4R arm, completion is defined as 120 doses within a maximum of 20 weeks, with no interruptions longer than two weeks on more than two occasions.

Secondary endpoints include the proportion of participants who permanently discontinue the assigned treatment due to adverse events, both related and unrelated to the study treatment, and the crude mortality rate, which is the number of participants who die while on the study. These efficacy parameters will be collected and analyzed to determine the relative effectiveness of the treatment regimens in achieving completion and managing adverse events. The trial aims to provide insights into the long-term efficacy and safety of these regimens in a specific patient population.