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

Background Rifampicin-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-li...

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Published in:Current controlled trials in cardiovascular medicine Vol. 23; no. 1; pp. 1011 - 14
Main Authors: Souleymane, Mahamadou Bassirou, Decroo, Tom, Soumana, Alphazazi, Maman Lawan, Ibrahim, Gagara-Issoufou, Assiatou, Halidou-Moussa, Souleymane, Ortuño-Gutiérrez, Nimer, Adehossi, Eric, Mamadou, Saïdou, Van Deun, Armand, Piubello, Alberto
Format: Journal Article
Language:English
Published: London BioMed Central 13.12.2022
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Abstract Background Rifampicin-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. Methods A 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. Discussion To 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. Trial registration Pan African Clinical Trial Register PACTR202203645724919 . Registered on 15 March 2022.
AbstractList Abstract Background Rifampicin-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. Methods A 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. Discussion To 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. Trial registration Pan African Clinical Trial Register PACTR202203645724919 . Registered on 15 March 2022.
Background Rifampicin-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. Methods A 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. Discussion To 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. Trial registration Pan African Clinical Trial Register PACTR202203645724919. Registered on 15 March 2022. Keywords: Rifampicin resistance tuberculosis, All oral treatment, New anti-tuberculosis drugs, Niger
Rifampicin-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.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.A 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.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.To 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.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.Pan African Clinical Trial Register PACTR202203645724919 . Registered on 15 March 2022.TRIAL REGISTRATIONPan African Clinical Trial Register PACTR202203645724919 . Registered on 15 March 2022.
Rifampicin-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. A 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. To 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. Pan African Clinical Trial Register PACTR202203645724919 . Registered on 15 March 2022.
Background Rifampicin-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. Methods A 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. Discussion To 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. Trial registration Pan African Clinical Trial Register PACTR202203645724919 . Registered on 15 March 2022.
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.Trial registrationPan African Clinical Trial Register PACTR202203645724919. Registered on 15 March 2022.
Rifampicin-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. A 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. To 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.
ArticleNumber 1011
Audience Academic
Author Decroo, Tom
Gagara-Issoufou, Assiatou
Van Deun, Armand
Halidou-Moussa, Souleymane
Mamadou, Saïdou
Piubello, Alberto
Ortuño-Gutiérrez, Nimer
Adehossi, Eric
Souleymane, Mahamadou Bassirou
Maman Lawan, Ibrahim
Soumana, Alphazazi
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/36514153$$D View this record in MEDLINE/PubMed
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CitedBy_id crossref_primary_10_1093_ofid_ofaf020
crossref_primary_10_1016_j_cegh_2024_101604
crossref_primary_10_5588_ijtldopen_25_0151
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Issue 1
Keywords New anti-tuberculosis drugs
All oral treatment
Niger
Rifampicin resistance tuberculosis
Language English
License 2022. The Author(s).
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PublicationDate 2022-12-13
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PublicationTitle Current controlled trials in cardiovascular medicine
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References 6912_CR7
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S Horter (6912_CR18) 2014; 14
NA Ismail (6912_CR13) 2022; 22
6912_CR11
A Piubello (6912_CR5) 2014; 18
PPJ Phillips (6912_CR21) 2019; 16
6912_CR15
A Van Deun (6912_CR4) 2010; 182
World Health Organization (6912_CR12) 2020
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Snippet Background Rifampicin-resistant tuberculosis (RR-TB) treatment requires combination treatment, which frequently causes serious adverse events and globally...
Rifampicin-resistant tuberculosis (RR-TB) treatment requires combination treatment, which frequently causes serious adverse events and globally results in not...
Background Rifampicin-resistant tuberculosis (RR-TB) treatment requires combination treatment, which frequently causes serious adverse events and globally...
BackgroundRifampicin-resistant tuberculosis (RR-TB) treatment requires combination treatment, which frequently causes serious adverse events and globally...
Abstract Background Rifampicin-resistant tuberculosis (RR-TB) treatment requires combination treatment, which frequently causes serious adverse events and...
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SubjectTerms All oral treatment
Antitubercular agents
Antitubercular Agents - adverse effects
Audiometry
Biomedicine
Care and treatment
Clinical trials
Contraindications
Corporate sponsorship
Diagnosis
Dosage and administration
Drugs
Evaluation
Health Sciences
Hearing loss
Humans
Informed consent
Laboratories
Linezolid - adverse effects
Medicine
Medicine & Public Health
New anti-tuberculosis drugs
Niger
Patient compliance
Patient outcomes
Patients
Randomized Controlled Trials as Topic
Rifampicin resistance tuberculosis
Rifampin - adverse effects
Statistics for Life Sciences
Study Protocol
Success
Testing
Tuberculosis
Tuberculosis, Multidrug-Resistant - diagnosis
Tuberculosis, Multidrug-Resistant - drug therapy
Tuberculosis, Pulmonary - diagnosis
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Title 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
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