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

Официальное название

Research on Evaluating Rifapentine-Based Shorter Regimens for Tuberculosis and Tuberculosis Infection Among People Living With and Without HIV in Programmatic Settings in Kazakhstan (RIFA-REAL)

Обзор

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.

Подробное описание

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).

Первичные конечные точки

• Favourable Treatment Outcome at 12 Months (DS-TB Cohorts) [Срок оценки: 12 months from treatment initiation]

Вторичные конечные точки (2)

• Cumulative Incidence of Serious Adverse Events [Срок оценки: Up to 4 months]
• Treatment completion rate [Срок оценки: Up to 4 months]

Критерии участия

Критерии включения

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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Dorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, Engle M, Goldberg SV, Phan HTT, Hakim J, Johnson JL, Lourens M, Martinson NA, Muzanyi G, Narunsky K, Nerette S, Nguyen NV, Pham TH, Pierre S, Purfield AE, Samaneka W, Savic RM, Sanne I, Scott NA, Shenje J, Sizemore E, Vernon A, Waja Z, Weiner M, Swindells S, Chaisson RE; AIDS Clinical Trials Group; Tuberculosis Trials Consortium. PMID 33951360
• 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 Tubercul PMID 30865794

Идентификаторы

NCT: NCT07668479 · RIFA-REAL-KZ-2026

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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