An Adaptive Randomized Controlled Trial

Официальное название

Adaptive Evaluation of mHealth and Conventional Adherence Support Interventions to Optimize Outcome With New Treatment Regimens for Drug-resistant Tuberculosis and HIV in South Africa

Обзор

This is a prospective, adaptive, randomized controlled trial comparing the effectiveness of 4 intervention arms on a combined endpoint in adults with confirmed MDR-TB HIV initiating Bedaquiline-containing MDR-TB treatment regimens and on ART (integrase strand transfer inhibitor (INSTI)-based fixed dose combination therapy) in KwaZulu-Natal, South Africa. Interventions arms include: enhanced standard of care; psychosocial support; mHealth using cellular-enabled electronic dose monitoring; combined mHealth psychosocial support. Level of support will be adjusted using a differentiated service delivery (DSD)- informed assessment of treatment support needs.

Подробное описание

This study will follow a 4-arm Bayesian, adaptive trial design. As patients are enrolled, they will be randomized into one of the four arms.

The study will be carried out within a common structure to allow for efficient enrollment and analysis. The overall structure is a 4-arm adaptive platform of mHealth and psychosocial adherence support interventions informed by a differentiated service delivery (DSD) approach.

Aim 1 is an adaptive study of mHealth and psychosocial adherence support interventions using a Bayesian adaptive design to allow comparison of elements of the intervention separately and in combination. Aim 1 participants will be randomized into one of 4 arms and followed monthly through the 6 months of intervention, then through the end of treatment telephonically, with an additional in-person visit to establish the primary outcome. Primary outcome is a combined clinical/biological outcome at 12 months described below. Hypothesis 1a utilizes all participants while 1b utilizes only those in the mHealth intervention arms (3+4) since granular EDM-measured adherence is required.

Вмешательства

• Поведенческое Adherence support intevention
  Compare the effects of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform.

Первичные конечные точки

• Biological outcome [Срок оценки: 06 months]
• Clinical outcome [Срок оценки: 12 months]
• Biological outcome [Срок оценки: 12 months]
• Clinical outcome [Срок оценки: 12 months]
• Biological outcome [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Culture or molecular test positive for MTB
• Molecular test positive for HIV or a documented HIV positive history
• Drug-susceptibility testing by molecular (i.e. GeneXpert MTB/RIF) or conventional testing consistent with at least rifampicin-resistant TB,
• Initiating treatment with a Bedaquiline -containing TB regimen within 4 weeks of enrollment and first-time being treated with BDQ
• On treatment with Antiretroviral Therapy (ART) regimen, including dolutegravir-containing combination Antiretroviral Therapy regimen (i.e. Tenofovir-Lamivudine-Dolutergravir), or starting within 4 weeks of enrollment,
• Capacity for informed consent in either isiZulu or English

Критерии исключения

• Pregnancy
• Prisoners
• Discretion of IOR or clinician

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Поддерживающая терапия

Центры проведения

ЮАР · 1 центр

• King DinuZulu Hospital — Durban

Публикации

• Diacon AH, Pym A, Grobusch MP, de los Rios JM, Gotuzzo E, Vasilyeva I, Leimane V, Andries K, Bakare N, De Marez T, Haxaire-Theeuwes M, Lounis N, Meyvisch P, De Paepe E, van Heeswijk RP, Dannemann B; TMC207-C208 Study Group. Multidrug-resistant tuberculosis and culture conversion with bedaquiline. N Engl J Med. 2014 Aug 21;371(8):723-32. doi: 10.1056/NEJMoa1313865. PMID 25140958
• O'Donnell MR, Padayatchi N, Daftary A, Orrell C, Dooley KE, Rivet Amico K, Friedland G. Antiretroviral switching and bedaquiline treatment of drug-resistant tuberculosis HIV co-infection. Lancet HIV. 2019 Mar;6(3):e201-e204. doi: 10.1016/S2352-3018(19)30035-9. PMID 30846058
• Calmy A, Tovar Sanchez T, Kouanfack C, Mpoudi-Etame M, Leroy S, Perrineau S, Lantche Wandji M, Tetsa Tata D, Omgba Bassega P, Abong Bwenda T, Varloteaux M, Tongo M, Mpoudi-Ngole E, Montoyo A, Mercier N, LeMoing V, Peeters M, Reynes J, Delaporte E; New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-Income Countries (NAMSAL) ANRS 12313 Study Group. Dolutegravir-based and low- PMID 33010241
• NAMSAL ANRS 12313 Study Group; Kouanfack C, Mpoudi-Etame M, Omgba Bassega P, Eymard-Duvernay S, Leroy S, Boyer S, Peeters M, Calmy A, Delaporte E. Dolutegravir-Based or Low-Dose Efavirenz-Based Regimen for the Treatment of HIV-1. N Engl J Med. 2019 Aug 29;381(9):816-826. doi: 10.1056/NEJMoa1904340. Epub 2019 Jul 24. PMID 31339676
• Nimmo C, Millard J, Brien K, Moodley S, van Dorp L, Lutchminarain K, Wolf A, Grant AD, Balloux F, Pym AS, Padayatchi N, O'Donnell M. Bedaquiline resistance in drug-resistant tuberculosis HIV co-infected patients. Eur Respir J. 2020 Jun 4;55(6):1902383. doi: 10.1183/13993003.02383-2019. Print 2020 Jun. PMID 32060065
• Nimmo C, Millard J, van Dorp L, Brien K, Moodley S, Wolf A, Grant AD, Padayatchi N, Pym AS, Balloux F, O'Donnell M. Population-level emergence of bedaquiline and clofazimine resistance-associated variants among patients with drug-resistant tuberculosis in southern Africa: a phenotypic and phylogenetic analysis. Lancet Microbe. 2020 Aug;1(4):e165-e174. doi: 10.1016/S2666-5247(20)30031-8. PMID 32803174
• WHO. World Health Organization. Global tuberculosis report 2020. 2020.
• Saunders MJ, Evans CA. COVID-19, tuberculosis and poverty: preventing a perfect storm. Eur Respir J. 2020 Jul 9;56(1):2001348. doi: 10.1183/13993003.01348-2020. Print 2020 Jul. PMID 32444399

Идентификаторы

NCT: NCT05633056 · AAAT8513 · CAP262 · 1R01AI167795

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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