TY - JOUR
T1 - Safety, effectiveness, and adherence of a short and all-oral treatment regimen for the treatment of rifampicin-resistant tuberculosis in Niger: a study protocol of a pragmatic randomised clinical trial with stratified block randomisation
AU - Souleymane, Mahamadou Bassirou
AU - Decroo, Tom
AU - Soumana, Alphazazi
AU - Lawan, Ibrahim Maman
AU - Gagara-Issoufou, Assiatou
AU - Halidou-Moussa, Souleymane
AU - Ortuno-Gutierrez, Nimer
AU - Adehossi, Eric
AU - Mamadou, Saidou
AU - Van Deun, Armand
AU - Piubello, Alberto
N1 - FTX; (CC BY 4.0)
PY - 2022
Y1 - 2022
N2 - BackgroundRifampicin-resistant tuberculosis (RR-TB) treatment requires combination treatment, which frequently causes serious adverse events and globally results in not much more than 60% treatment success. In Niger, a high cure rate was obtained with a RR-TB treatment strategy based on a second-line injectable drug (SLID)-containing Short Treatment Regimen (STR), with linezolid replacing the SLID in patients with ototoxicity. Given the availability of novel anti-tuberculosis drugs, WHO recommends all-oral RR-TB treatment. Considering the high level of success with the Niger treatment strategy, it would only be justified to replace it in case robust evidence shows that the WHO all-oral bedaquiline/linezolid (BDQ/LZD)-containing STR (experimental arm) performs better than the Niger RR-TB treatment strategy, (control arm) in terms of safety, effectiveness and adherence. MethodsA pragmatic randomised clinical trial (RCT) using stratified block randomisation, conducted between April 2021 and March 2024, prospectively enrols participants diagnosed with RR-TB in one of the four RR-TB units of the nation. Depending of the month in which patients are diagnosed with RR-TB, patients with FQ-susceptible RR-TB are enrolled in either the experimental arm or control arm. DiscussionTo increase the feasibility of conducting a RCT, embedded in routine activities of all Niger's RR-TB Units, we used a creative trial design. We randomised by monthly blocks, whereby the regimen used changes every month, using the month of RR-TB diagnosis as stratifying variable. This approach was deemed feasible for Niger's national tuberculosis programme, as it simplifies the work of the clinicians running the RR-TB units. Our creative design may serve as an example for other national programs. Findings will inform national and international RR-TB treatment guidelines, and will also strengthen the evidence-base on how to develop robust RR-TB treatment regimens.
AB - BackgroundRifampicin-resistant tuberculosis (RR-TB) treatment requires combination treatment, which frequently causes serious adverse events and globally results in not much more than 60% treatment success. In Niger, a high cure rate was obtained with a RR-TB treatment strategy based on a second-line injectable drug (SLID)-containing Short Treatment Regimen (STR), with linezolid replacing the SLID in patients with ototoxicity. Given the availability of novel anti-tuberculosis drugs, WHO recommends all-oral RR-TB treatment. Considering the high level of success with the Niger treatment strategy, it would only be justified to replace it in case robust evidence shows that the WHO all-oral bedaquiline/linezolid (BDQ/LZD)-containing STR (experimental arm) performs better than the Niger RR-TB treatment strategy, (control arm) in terms of safety, effectiveness and adherence. MethodsA pragmatic randomised clinical trial (RCT) using stratified block randomisation, conducted between April 2021 and March 2024, prospectively enrols participants diagnosed with RR-TB in one of the four RR-TB units of the nation. Depending of the month in which patients are diagnosed with RR-TB, patients with FQ-susceptible RR-TB are enrolled in either the experimental arm or control arm. DiscussionTo increase the feasibility of conducting a RCT, embedded in routine activities of all Niger's RR-TB Units, we used a creative trial design. We randomised by monthly blocks, whereby the regimen used changes every month, using the month of RR-TB diagnosis as stratifying variable. This approach was deemed feasible for Niger's national tuberculosis programme, as it simplifies the work of the clinicians running the RR-TB units. Our creative design may serve as an example for other national programs. Findings will inform national and international RR-TB treatment guidelines, and will also strengthen the evidence-base on how to develop robust RR-TB treatment regimens.
KW - Rifampicin resistance tuberculosis
KW - All oral treatment
KW - New anti-tuberculosis drugs
KW - Niger
U2 - 10.1186/s13063-022-06912-7
DO - 10.1186/s13063-022-06912-7
M3 - A1: Web of Science-article
SN - 1745-6215
VL - 23
JO - Trials
JF - Trials
IS - 1
M1 - 1011
ER -