Triage test for all-oral drug-resistant tuberculosis (DR-TB) regimen: a phase IV study to assess effectiveness, feasibility, acceptability and cost-effectiveness of the Xpert MTB/XDR assay for rapid triage and treatment of DR-TB
Introduction The TriAD study will assess the Xpert MTB/XDR (Xpert XDR; Cepheid) assay to detect tuberculosis (TB) drug resistance in sputum testing positive for TB to rapidly triage and treat patients with a short all-oral treatment regimen.Methods and analysis In this study, approximately 4800 Xper...
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2024-11-01
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| author | Kogieleum Naidoo Derek J Sloan Wilber Sabiiti Bariki Mtafya Stephen H Gillespie Aderonke Agbaje Nyanda Elias Ntinginya Morten Ruhwald Agnes Gebhard Anushka Naidoo Rubeshan Perumal Getachew Tollera Evaezi Okpokoro Alash'le G Abimiku Everdina W Tiemersma Sabine M Hermans Sophia B Georghiou Kalkidan Yae Shewki Moga Hannelise Feyt Takondwa Kachoka Marothi P Letsoalo Andrea M Cabibbe Letitia Shunmugam Daniela M Cirillo Salah Foraida |
| author_facet | Kogieleum Naidoo Derek J Sloan Wilber Sabiiti Bariki Mtafya Stephen H Gillespie Aderonke Agbaje Nyanda Elias Ntinginya Morten Ruhwald Agnes Gebhard Anushka Naidoo Rubeshan Perumal Getachew Tollera Evaezi Okpokoro Alash'le G Abimiku Everdina W Tiemersma Sabine M Hermans Sophia B Georghiou Kalkidan Yae Shewki Moga Hannelise Feyt Takondwa Kachoka Marothi P Letsoalo Andrea M Cabibbe Letitia Shunmugam Daniela M Cirillo Salah Foraida |
| author_sort | Kogieleum Naidoo |
| collection | DOAJ |
| description | Introduction The TriAD study will assess the Xpert MTB/XDR (Xpert XDR; Cepheid) assay to detect tuberculosis (TB) drug resistance in sputum testing positive for TB to rapidly triage and treat patients with a short all-oral treatment regimen.Methods and analysis In this study, approximately 4800 Xpert MTB/RIF or Ultra MTB-positive patients (irrespective of rifampicin (RIF) resistance (RR) status) from several clinical sites across South Africa, Nigeria and Ethiopia will be enrolled over 18–24 months and followed-up for approximately 6 months post-TB treatment completion. Participants will be enrolled into one of two cohorts based on Xpert MTB/RIF and Xpert XDR results: Mycobacterium tuberculosis (M.tb) positive participants with RR in Cohort 1 (n=880) and M.tb positive RIF susceptible TB patients with isoniazid mono-resistance irrespective of presence of resistance to fluoroquinolones, second-line injectable drugs or ethionamide in Cohort 2 (n=400). Cohort 1 will be compared with historical cohorts from each implementing sites. The primary study outcomes include time to initiation of an appropriate treatment regimen by resistance profile and the proportion of patients with favourable treatment outcomes compared with historical cohorts from each of the implementing sites. Secondary outcomes include feasibility, acceptability and cost-effectiveness of this approach to inform policies and guidelines for programmatic implementation of this triage and treat model for drug-resistant tuberculosis management. Utility of the tuberculosis molecular bacterial load assay (TB-MBLA) for real-time treatment response assessment will also be evaluated.Ethics and dissemination The University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC) and local research committees have provided ethical review and approval (BREC/00002654/2021, HREC 210805, NHREC/01/01/2007 and EPHI-IRB-459–2022). The South African Health Products Regulatory Authority (SAHPRA) have granted regulatory approval for the TRiAD Study (SAHPRA MD20211001). Trial results will be disseminated through conference presentations, peer-reviewed publications and the clinical trial registry.Trial registration number Clinicaltrials.gov; Trial registration number: NCT05175794; South African National Clinical Trials Register (SANCTR DOH-27-012022-4720) |
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| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj-art-60b790803fe740e38bf35d2caac7d34f2024-12-13T14:00:09ZengBMJ Publishing GroupBMJ Open2044-60552024-11-01141110.1136/bmjopen-2024-084722Triage test for all-oral drug-resistant tuberculosis (DR-TB) regimen: a phase IV study to assess effectiveness, feasibility, acceptability and cost-effectiveness of the Xpert MTB/XDR assay for rapid triage and treatment of DR-TBKogieleum Naidoo0Derek J Sloan1Wilber Sabiiti2Bariki Mtafya3Stephen H Gillespie4Aderonke Agbaje5Nyanda Elias Ntinginya6Morten Ruhwald7Agnes Gebhard8Anushka Naidoo9Rubeshan Perumal10Getachew Tollera11Evaezi Okpokoro12Alash'le G Abimiku13Everdina W Tiemersma14Sabine M Hermans15Sophia B Georghiou16Kalkidan Yae17Shewki Moga18Hannelise Feyt19Takondwa Kachoka20Marothi P Letsoalo21Andrea M Cabibbe22Letitia Shunmugam23Daniela M Cirillo24Salah Foraida252 SAMRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa7 University of St Andrews, St Andrews, UK7 University of St Andrews, St Andrews, UK14 National Institute for Medical Research, Dar es Salaam, United Republic of Tanzania7 University of St Andrews, St Andrews, UK3 International Research Center of Excellence, Institute of Human Virology Nigeria, Abuja, Nigeria14 National Institute for Medical Research, Dar es Salaam, United Republic of Tanzania8 Foundation for Innovative New Diagnostics, Geneva, Switzerland5 Koninklijke Nederlandse Centrale Vereniging tot Bestrijding der Tuberculose, The Hague, The Netherlands1 Centre for the Aids Programme of Research in South Africa, Durban, KwaZulu-Natal, South Africa1 Centre for the Aids Programme of Research in South Africa, Durban, KwaZulu-Natal, South Africa10 Ethiopian Public Health Institute, Addis Ababa, Ethiopia3 International Research Center of Excellence, Institute of Human Virology Nigeria, Abuja, Nigeria3 International Research Center of Excellence, Institute of Human Virology Nigeria, Abuja, Nigeria5 Koninklijke Nederlandse Centrale Vereniging tot Bestrijding der Tuberculose, The Hague, The Netherlands6 Amsterdam UMC location University of Amsterdam, Department of Global Health, Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands8 Foundation for Innovative New Diagnostics, Geneva, Switzerland9 Koninklijke Nederlandse Centrale Vereniging tot Bestrijding der Tuberculose, Addis Ababa, Ethiopia10 Ethiopian Public Health Institute, Addis Ababa, Ethiopia11 Clinical HIV Research Unit (CHRU), Jose Pearson TB Hospital, Wits Health Consortium Pty Ltd, Port Elizabeth, South Africa11 Clinical HIV Research Unit (CHRU), Jose Pearson TB Hospital, Wits Health Consortium Pty Ltd, Port Elizabeth, South Africa1 Centre for the Aids Programme of Research in South Africa, Durban, KwaZulu-Natal, South Africa12 Emerging bacterial pathogens, Ospedale San Raffaele, Milano, Italy1 Centre for the Aids Programme of Research in South Africa, Durban, KwaZulu-Natal, South Africa12 Emerging bacterial pathogens, Ospedale San Raffaele, Milano, Italy13 Global Alliance for TB Drug Development, New York, New York, USAIntroduction The TriAD study will assess the Xpert MTB/XDR (Xpert XDR; Cepheid) assay to detect tuberculosis (TB) drug resistance in sputum testing positive for TB to rapidly triage and treat patients with a short all-oral treatment regimen.Methods and analysis In this study, approximately 4800 Xpert MTB/RIF or Ultra MTB-positive patients (irrespective of rifampicin (RIF) resistance (RR) status) from several clinical sites across South Africa, Nigeria and Ethiopia will be enrolled over 18–24 months and followed-up for approximately 6 months post-TB treatment completion. Participants will be enrolled into one of two cohorts based on Xpert MTB/RIF and Xpert XDR results: Mycobacterium tuberculosis (M.tb) positive participants with RR in Cohort 1 (n=880) and M.tb positive RIF susceptible TB patients with isoniazid mono-resistance irrespective of presence of resistance to fluoroquinolones, second-line injectable drugs or ethionamide in Cohort 2 (n=400). Cohort 1 will be compared with historical cohorts from each implementing sites. The primary study outcomes include time to initiation of an appropriate treatment regimen by resistance profile and the proportion of patients with favourable treatment outcomes compared with historical cohorts from each of the implementing sites. Secondary outcomes include feasibility, acceptability and cost-effectiveness of this approach to inform policies and guidelines for programmatic implementation of this triage and treat model for drug-resistant tuberculosis management. Utility of the tuberculosis molecular bacterial load assay (TB-MBLA) for real-time treatment response assessment will also be evaluated.Ethics and dissemination The University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC) and local research committees have provided ethical review and approval (BREC/00002654/2021, HREC 210805, NHREC/01/01/2007 and EPHI-IRB-459–2022). The South African Health Products Regulatory Authority (SAHPRA) have granted regulatory approval for the TRiAD Study (SAHPRA MD20211001). Trial results will be disseminated through conference presentations, peer-reviewed publications and the clinical trial registry.Trial registration number Clinicaltrials.gov; Trial registration number: NCT05175794; South African National Clinical Trials Register (SANCTR DOH-27-012022-4720)https://bmjopen.bmj.com/content/14/11/e084722.full |
| spellingShingle | Kogieleum Naidoo Derek J Sloan Wilber Sabiiti Bariki Mtafya Stephen H Gillespie Aderonke Agbaje Nyanda Elias Ntinginya Morten Ruhwald Agnes Gebhard Anushka Naidoo Rubeshan Perumal Getachew Tollera Evaezi Okpokoro Alash'le G Abimiku Everdina W Tiemersma Sabine M Hermans Sophia B Georghiou Kalkidan Yae Shewki Moga Hannelise Feyt Takondwa Kachoka Marothi P Letsoalo Andrea M Cabibbe Letitia Shunmugam Daniela M Cirillo Salah Foraida Triage test for all-oral drug-resistant tuberculosis (DR-TB) regimen: a phase IV study to assess effectiveness, feasibility, acceptability and cost-effectiveness of the Xpert MTB/XDR assay for rapid triage and treatment of DR-TB BMJ Open |
| title | Triage test for all-oral drug-resistant tuberculosis (DR-TB) regimen: a phase IV study to assess effectiveness, feasibility, acceptability and cost-effectiveness of the Xpert MTB/XDR assay for rapid triage and treatment of DR-TB |
| title_full | Triage test for all-oral drug-resistant tuberculosis (DR-TB) regimen: a phase IV study to assess effectiveness, feasibility, acceptability and cost-effectiveness of the Xpert MTB/XDR assay for rapid triage and treatment of DR-TB |
| title_fullStr | Triage test for all-oral drug-resistant tuberculosis (DR-TB) regimen: a phase IV study to assess effectiveness, feasibility, acceptability and cost-effectiveness of the Xpert MTB/XDR assay for rapid triage and treatment of DR-TB |
| title_full_unstemmed | Triage test for all-oral drug-resistant tuberculosis (DR-TB) regimen: a phase IV study to assess effectiveness, feasibility, acceptability and cost-effectiveness of the Xpert MTB/XDR assay for rapid triage and treatment of DR-TB |
| title_short | Triage test for all-oral drug-resistant tuberculosis (DR-TB) regimen: a phase IV study to assess effectiveness, feasibility, acceptability and cost-effectiveness of the Xpert MTB/XDR assay for rapid triage and treatment of DR-TB |
| title_sort | triage test for all oral drug resistant tuberculosis dr tb regimen a phase iv study to assess effectiveness feasibility acceptability and cost effectiveness of the xpert mtb xdr assay for rapid triage and treatment of dr tb |
| url | https://bmjopen.bmj.com/content/14/11/e084722.full |
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