Rifapentine-Based Shorter Regimens for Tuberculosis and TB Infection in Kazakhstan

N/ANot Yet RecruitingNCT07668479

Public Union "Kazakhstan Association of Phthisiopulmonologists"350 enrolled

Overview

RIFA-REAL is a prospective observational longitudinal study evaluating the safety, feasibility, and effectiveness of rifapentine-based shorter treatment regimens for drug-susceptible tuberculosis (DS-TB) and tuberculosis infection (TBI) under routine programmatic conditions in Kazakhstan. The study enrolls three cohorts: patients with DS-TB receiving the 4-month isoniazid-rifapentine-moxifloxacin-pyrazinamide regimen (2HPMZ/2HPM), patients with DS-TB receiving the standard 6-month isoniazid-rifampicin-pyrazinamide-ethambutol regimen (2HRZE/4HR), and individuals with TBI receiving the 1-month rifapentine-isoniazid regimen (1HP). Participants include people living with and without HIV. The study is conducted across four regions of Kazakhstan and is funded through the Western-Eastern European Partnership Initiative on HIV, Viral Hepatitis and TB (WEEPI) grant. Findings will inform national TB policy and contribute to global evidence on programmatic implementation of rifapentine-based regimens.

Despite World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), and European Respiratory Society (ERS) recommendations, uptake of shorter rifapentine-based regimens for DS-TB (2HPMZ/2HPM) and TBI (1HP) remains limited due to concerns about adverse events and lack of real-world implementation evidence. This study prospectively follows three cohorts over 12 months from treatment initiation. Primary outcomes include favourable treatment outcomes at 12 months (DS-TB cohorts), cumulative incidence and severity of serious adverse events (all cohorts), and key feasibility indicators including recruitment rates, retention, adherence, and treatment completion. The study was approved by the Local Bioethics Committee of the National Center for Public Health, Ministry of Health of Kazakhstan (Protocol No. 2026-LKB-004-P, 29 April 2026).

Study Type

OBSERVATIONAL

Enrollment

350

Conditions

Tuberculosis Tuberculosis Infection, Latent

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: FOR DS-TB COHORTS (2HPMZ/2HPM and 2HRZE/4HR): * Age 18 years or older * Bacteriologically confirmed drug-susceptible pulmonary tuberculosis * Newly diagnosed, not previously treated (or treated less than 1 month) * Willing and able to provide written informed consent * Residing in one of the four pilot regions of Kazakhstan FOR TBI COHORT (1HP): * Age 18 years or older * Diagnosed with tuberculosis infection * No evidence of active tuberculosis disease * Willing and able to provide written informed consent * Residing in one of the four pilot regions of Kazakhstan Exclusion Criteria: FOR DS-TB COHORTS: * Confirmed or suspected drug-resistant tuberculosis (rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant tuberculosis (MDR-TB)) * Extrapulmonary tuberculosis as the sole manifestation * Pregnancy or breastfeeding at time of enrollment * Severe hepatic impairment (alanine aminotransferase (ALT)/aspartate aminotransferase (AST) \>3x upper limit of normal) * Known hypersensitivity to rifapentine, isoniazid, moxifloxacin, or pyrazinamide * corrected QT interval (QTc) interval \>500 ms on baseline electrocardiogram (ECG) * Currently receiving medications with significant interactions contraindicated with study regimens FOR TBI COHORT: * Active tuberculosis disease * Previous treatment for TB or TBI within the past 2 years * Pregnancy at time of enrollment * Severe hepatic impairment * Known hypersensitivity to rifapentine or isoniazid

Outcomes

Primary Outcomes

Favourable Treatment Outcome at 12 Months (DS-TB Cohorts)

Proportion of patients with drug-susceptible tuberculosis who achieve a favourable treatment outcome, defined as "cured" or "treatment completed" without recurrence, within 12 months of treatment initiation. Compared between 2HPMZ/2HPM and standard 2HRZE/4HR cohorts.

Time frame: 12 months from treatment initiation

Secondary Outcomes

Cumulative Incidence of Serious Adverse Events

Cumulative incidence rate, timing of onset, severity, and outcomes of all serious adverse events recorded during treatment in the 2HPMZ/2HPM and 1HP cohorts. Treatment duration is up to 4 months for 2HPMZ/2HPM and up to 1 month for 1HP.

Time frame: Up to 4 months

Treatment completion rate

Percentage of participants who complete the full assigned regimen (2HPMZ/2HPM or 1HP) without premature discontinuation, measured from treatment initiation through the end of the assigned regimen.