Project Details
Description
Rifampicin-resistant tuberculosis (RR-TB) poses a significant global health challenge, particularly in low-resource settings like Niger. Despite advancements in diagnostic tools and the advent of new TB drugs, RR-TB treatment outcomes remain suboptimal, with high rates of mortality, loss to follow-up (LTFU). This PhD project aims to improve the safety and success of RR-TB treatment in Niger by addressing key challenges associated with current treatment regimens.
Since the introduction of Xpert MTB/RIF (Xpert) in 2014 and the shift in 2021 to all-oral regimens, containing bedaquiline (BDQ; B), linezolid (LZD; L), high-dose levofloxacin (LFX) plus others, Niger has seen significant improvements in RR-TB diagnosis, treatment uptake, but treatment outcomes have not improved as expected. However, frequent severe adverse events of specific interest (sAESI), particularly those associated with LZD, have raised concerns about treatment success and patient adherence with an increased rate of LTFU. In response, this research focuses on three key objectives: 1) comparing the efficacy and safety of a LZD-free modified STREAM2 regimen with the standard of care BPaLM regimen, 2) investigating the relationship between sAESI and LTFU among RR-TB patients, and 3) evaluating the safety and effectiveness of treatment for highly drug-resistant TB, including pre-extensively drug-resistant (pre-XDR) and extensively drug-resistant (XDR) TB in Niger.
The first objective will be addressed through a pragmatic cluster-randomized clinical trial comparing the LZD-free modified STREAM2 regimen which contains a second-line injectable (SLI), BDQ, LFX high dose, high-dose isoniazid (INHh), clofazimine (CFZ), and pyrazinamide (PZA) with BPaLM. The modified regimen replaces LZD with amikacin (AMK) an SLI for two weeks, aiming to minimize toxicity while maintaining efficacy. The trial hypothesizes that the LZD-free modified STREAM 2 regimen will reduce sAESI rates, enhance patient adherence, and improve treatment outcomes. This study also has the potential to shorten the treatment regimen duration for most patients from six to five months, further reducing the treatment burden like treatment costs and increasing the retention in care.
The second objective involves a retrospective analysis of RR-TB patients treated between 2015 and 2023 to assess the impact of sAESI on LTFU. Since the introduction of the all-oral regimen in 2021, LTFU rates in Niger have increased, potentially due to the rise of sAESI associated with LZD-containing regimens. This study will provide critical insights into the link between these sAESI and LTFU and could offer strategies for improving patient retention and treatment completion. It could also pave the way for the development of safer treatment regimens and could lead to guideline changes.
The third objective focuses on highly drug-resistant TB, including pre-XDR and XDR-TB cases reported in Niger since 2011. This retrospective study will evaluate the safety and effectiveness of treatment regimens for these complex cases, contributing to a better understanding of drug resistance patterns and informing future treatment strategies.
Since the introduction of Xpert MTB/RIF (Xpert) in 2014 and the shift in 2021 to all-oral regimens, containing bedaquiline (BDQ; B), linezolid (LZD; L), high-dose levofloxacin (LFX) plus others, Niger has seen significant improvements in RR-TB diagnosis, treatment uptake, but treatment outcomes have not improved as expected. However, frequent severe adverse events of specific interest (sAESI), particularly those associated with LZD, have raised concerns about treatment success and patient adherence with an increased rate of LTFU. In response, this research focuses on three key objectives: 1) comparing the efficacy and safety of a LZD-free modified STREAM2 regimen with the standard of care BPaLM regimen, 2) investigating the relationship between sAESI and LTFU among RR-TB patients, and 3) evaluating the safety and effectiveness of treatment for highly drug-resistant TB, including pre-extensively drug-resistant (pre-XDR) and extensively drug-resistant (XDR) TB in Niger.
The first objective will be addressed through a pragmatic cluster-randomized clinical trial comparing the LZD-free modified STREAM2 regimen which contains a second-line injectable (SLI), BDQ, LFX high dose, high-dose isoniazid (INHh), clofazimine (CFZ), and pyrazinamide (PZA) with BPaLM. The modified regimen replaces LZD with amikacin (AMK) an SLI for two weeks, aiming to minimize toxicity while maintaining efficacy. The trial hypothesizes that the LZD-free modified STREAM 2 regimen will reduce sAESI rates, enhance patient adherence, and improve treatment outcomes. This study also has the potential to shorten the treatment regimen duration for most patients from six to five months, further reducing the treatment burden like treatment costs and increasing the retention in care.
The second objective involves a retrospective analysis of RR-TB patients treated between 2015 and 2023 to assess the impact of sAESI on LTFU. Since the introduction of the all-oral regimen in 2021, LTFU rates in Niger have increased, potentially due to the rise of sAESI associated with LZD-containing regimens. This study will provide critical insights into the link between these sAESI and LTFU and could offer strategies for improving patient retention and treatment completion. It could also pave the way for the development of safer treatment regimens and could lead to guideline changes.
The third objective focuses on highly drug-resistant TB, including pre-XDR and XDR-TB cases reported in Niger since 2011. This retrospective study will evaluate the safety and effectiveness of treatment regimens for these complex cases, contributing to a better understanding of drug resistance patterns and informing future treatment strategies.
| Status | Active |
|---|---|
| Effective start/end date | 1/01/25 → … |
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