A pragmatic trial with an optimized dose of rifampicin and moxifloxacin for the treatment of drug-susceptible pulmonary tuberculosis: a study protocol for open-label, randomized phase III trial (OptiRiMoxTB)

Hamu J Mlyuka; Alphonce Liyoyo; Belinda Nyaulingo; Emmanuel Mpolya; Oscar L Kaswaga; Hadija Semvua; Samwel Lwambura; Tim D McHugh; Leticia Wildner; Wilber Sabiiti; Bayode R Adegbite; Marriot Nliwasa; Celso Khosa; Peter Mbelele; Benno Mbeya; Kidola Jeremiah; Martin J Boeree; Stephen H Gillespie; Derek J Sloan; Stellah G Mpagama; SimpliciTB Consortium

doi:10.1186/s13063-026-09466-0

A pragmatic trial with an optimized dose of rifampicin and moxifloxacin for the treatment of drug-susceptible pulmonary tuberculosis: a study protocol for open-label, randomized phase III trial (OptiRiMoxTB)

Hamu J Mlyuka, Alphonce Liyoyo, Belinda Nyaulingo, Emmanuel Mpolya, Oscar L Kaswaga, Hadija Semvua, Samwel Lwambura, Tim D McHugh, Leticia Wildner, Wilber Sabiiti, Bayode R Adegbite, Marriot Nliwasa, Celso Khosa, Peter Mbelele, Benno Mbeya, Kidola Jeremiah, Martin J Boeree, Stephen H Gillespie, Derek J Sloan, Stellah G Mpagama^*SimpliciTB Consortium

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Current combination antibiotic treatment for drug-susceptible tuberculosis (DS-TB) usually takes 6 months to complete. This long duration can compromise clinical outcomes. Although a 4-month regimen including an optimized dose of rifapentine plus moxifloxacin is non-inferior to standard therapy, rifapentine is hard to source globally and adoption of this regimen has been slow. This trial investigates the efficacy and safety of a 4-month DS-TB treatment including the more readily available rifamycin, rifampicin 35 mg/kg, with or without moxifloxacin 400 mg.

Methods: This multi-centre phase III randomized open-label clinical trial will be conducted across four African countries (Gabon, Malawi, Mozambique and Tanzania). A total of 414 newly diagnosed consenting adult participants will be block randomized, after stratification by chest radiograph cavitation, to two experimental and one control arm at a ratio of 1:1:1. The first experimental group will receive optimized dose rifampicin (35 mg/kg) with routine weight-banded doses of isoniazid, pyrazinamide, and ethambutol once daily for 4 months. The second experimental group will receive optimized dose rifampicin (35 mg/kg) and moxifloxacin 400 mg once daily alongside routine doses of isoniazid and pyrazinamide. The control group will receive 6-month standard of care therapy: rifampicin (10 mg/kg) plus weight-banded dose of isoniazid, pyrazinamide, and ethambutol for 2 months, followed by the same doses of rifampicin and isoniazid for 4 months. Participants will be followed until the allocation of efficacy (TB-free survival) and safety (proportion of severe adverse events) outcomes. Secondary outcomes will also include the evaluation of the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) for microbiological treatment monitoring.

Discussion: This study will evaluate whether 4-month duration multi-drug treatment including an optimized dose of rifampicin with or without moxifloxacin has non-inferior efficacy and safety outcomes compared to standard of care DS-TB therapy in Africa.

Original language	English
Article number	182
Pages (from-to)	1-14
Number of pages	14
Journal	Trials
Volume	27
Early online date	30 Jan 2026
DOIs	https://doi.org/10.1186/s13063-026-09466-0
Publication status	Published - 25 Feb 2026

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Optimized dose rifampicin
Moxifloxacin
Drug susceptible TB
TB-MBLA

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SimpliciTB - S Gillespie: EDCTP SimpliciTB 2018
Gillespie, S. (PI)
European and Developing Countries
1/01/19 → 31/12/22
Project: Standard

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Mlyuka, H. J., Liyoyo, A., Nyaulingo, B., Mpolya, E., Kaswaga, O. L., Semvua, H., Lwambura, S., McHugh, T. D., Wildner, L., Sabiiti, W., Adegbite, B. R., Nliwasa, M., Khosa, C., Mbelele, P., Mbeya, B., Jeremiah, K., Boeree, M. J., Gillespie, S. H., Sloan, D. J., ... SimpliciTB Consortium (2026). A pragmatic trial with an optimized dose of rifampicin and moxifloxacin for the treatment of drug-susceptible pulmonary tuberculosis: a study protocol for open-label, randomized phase III trial (OptiRiMoxTB). Trials, 27, 1-14. Article 182. https://doi.org/10.1186/s13063-026-09466-0

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title = "A pragmatic trial with an optimized dose of rifampicin and moxifloxacin for the treatment of drug-susceptible pulmonary tuberculosis: a study protocol for open-label, randomized phase III trial (OptiRiMoxTB)",

abstract = "Background: Current combination antibiotic treatment for drug-susceptible tuberculosis (DS-TB) usually takes 6 months to complete. This long duration can compromise clinical outcomes. Although a 4-month regimen including an optimized dose of rifapentine plus moxifloxacin is non-inferior to standard therapy, rifapentine is hard to source globally and adoption of this regimen has been slow. This trial investigates the efficacy and safety of a 4-month DS-TB treatment including the more readily available rifamycin, rifampicin 35 mg/kg, with or without moxifloxacin 400 mg.Methods: This multi-centre phase III randomized open-label clinical trial will be conducted across four African countries (Gabon, Malawi, Mozambique and Tanzania). A total of 414 newly diagnosed consenting adult participants will be block randomized, after stratification by chest radiograph cavitation, to two experimental and one control arm at a ratio of 1:1:1. The first experimental group will receive optimized dose rifampicin (35 mg/kg) with routine weight-banded doses of isoniazid, pyrazinamide, and ethambutol once daily for 4 months. The second experimental group will receive optimized dose rifampicin (35 mg/kg) and moxifloxacin 400 mg once daily alongside routine doses of isoniazid and pyrazinamide. The control group will receive 6-month standard of care therapy: rifampicin (10 mg/kg) plus weight-banded dose of isoniazid, pyrazinamide, and ethambutol for 2 months, followed by the same doses of rifampicin and isoniazid for 4 months. Participants will be followed until the allocation of efficacy (TB-free survival) and safety (proportion of severe adverse events) outcomes. Secondary outcomes will also include the evaluation of the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) for microbiological treatment monitoring.Discussion: This study will evaluate whether 4-month duration multi-drug treatment including an optimized dose of rifampicin with or without moxifloxacin has non-inferior efficacy and safety outcomes compared to standard of care DS-TB therapy in Africa.",

keywords = "Optimized dose rifampicin, Moxifloxacin, Drug susceptible TB, TB-MBLA",

author = "Mlyuka, \{Hamu J\} and Alphonce Liyoyo and Belinda Nyaulingo and Emmanuel Mpolya and Kaswaga, \{Oscar L\} and Hadija Semvua and Samwel Lwambura and McHugh, \{Tim D\} and Leticia Wildner and Wilber Sabiiti and Adegbite, \{Bayode R\} and Marriot Nliwasa and Celso Khosa and Peter Mbelele and Benno Mbeya and Kidola Jeremiah and Boeree, \{Martin J\} and Gillespie, \{Stephen H\} and Sloan, \{Derek J\} and Mpagama, \{Stellah G\} and \{SimpliciTB Consortium\}",

note = "Funding: The trial is funded by the Europe and Developing Countries Clinical Trials-2 (EDCTP2). Simplified short treatment for tuberculosis grant RIA2017S-2012.",

year = "2026",

month = feb,

day = "25",

doi = "10.1186/s13063-026-09466-0",

language = "English",

volume = "27",

pages = "1--14",

journal = "Trials",

issn = "1745-6215",

publisher = "BioMed Central",

}

Mlyuka, HJ, Liyoyo, A, Nyaulingo, B, Mpolya, E, Kaswaga, OL, Semvua, H, Lwambura, S, McHugh, TD, Wildner, L, Sabiiti, W, Adegbite, BR, Nliwasa, M, Khosa, C, Mbelele, P, Mbeya, B, Jeremiah, K, Boeree, MJ, Gillespie, SH , Sloan, DJ , Mpagama, SG & SimpliciTB Consortium 2026, 'A pragmatic trial with an optimized dose of rifampicin and moxifloxacin for the treatment of drug-susceptible pulmonary tuberculosis: a study protocol for open-label, randomized phase III trial (OptiRiMoxTB)', Trials, vol. 27, 182, pp. 1-14. https://doi.org/10.1186/s13063-026-09466-0

A pragmatic trial with an optimized dose of rifampicin and moxifloxacin for the treatment of drug-susceptible pulmonary tuberculosis: a study protocol for open-label, randomized phase III trial (OptiRiMoxTB). / Mlyuka, Hamu J; Liyoyo, Alphonce; Nyaulingo, Belinda et al.
In: Trials, Vol. 27, 182, 25.02.2026, p. 1-14.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - A pragmatic trial with an optimized dose of rifampicin and moxifloxacin for the treatment of drug-susceptible pulmonary tuberculosis

T2 - a study protocol for open-label, randomized phase III trial (OptiRiMoxTB)

AU - Mlyuka, Hamu J

AU - Liyoyo, Alphonce

AU - Nyaulingo, Belinda

AU - Mpolya, Emmanuel

AU - Kaswaga, Oscar L

AU - Semvua, Hadija

AU - Lwambura, Samwel

AU - McHugh, Tim D

AU - Wildner, Leticia

AU - Sabiiti, Wilber

AU - Adegbite, Bayode R

AU - Nliwasa, Marriot

AU - Khosa, Celso

AU - Mbelele, Peter

AU - Mbeya, Benno

AU - Jeremiah, Kidola

AU - Boeree, Martin J

AU - Gillespie, Stephen H

AU - Sloan, Derek J

AU - Mpagama, Stellah G

AU - SimpliciTB Consortium

N1 - Funding: The trial is funded by the Europe and Developing Countries Clinical Trials-2 (EDCTP2). Simplified short treatment for tuberculosis grant RIA2017S-2012.

PY - 2026/2/25

Y1 - 2026/2/25

N2 - Background: Current combination antibiotic treatment for drug-susceptible tuberculosis (DS-TB) usually takes 6 months to complete. This long duration can compromise clinical outcomes. Although a 4-month regimen including an optimized dose of rifapentine plus moxifloxacin is non-inferior to standard therapy, rifapentine is hard to source globally and adoption of this regimen has been slow. This trial investigates the efficacy and safety of a 4-month DS-TB treatment including the more readily available rifamycin, rifampicin 35 mg/kg, with or without moxifloxacin 400 mg.Methods: This multi-centre phase III randomized open-label clinical trial will be conducted across four African countries (Gabon, Malawi, Mozambique and Tanzania). A total of 414 newly diagnosed consenting adult participants will be block randomized, after stratification by chest radiograph cavitation, to two experimental and one control arm at a ratio of 1:1:1. The first experimental group will receive optimized dose rifampicin (35 mg/kg) with routine weight-banded doses of isoniazid, pyrazinamide, and ethambutol once daily for 4 months. The second experimental group will receive optimized dose rifampicin (35 mg/kg) and moxifloxacin 400 mg once daily alongside routine doses of isoniazid and pyrazinamide. The control group will receive 6-month standard of care therapy: rifampicin (10 mg/kg) plus weight-banded dose of isoniazid, pyrazinamide, and ethambutol for 2 months, followed by the same doses of rifampicin and isoniazid for 4 months. Participants will be followed until the allocation of efficacy (TB-free survival) and safety (proportion of severe adverse events) outcomes. Secondary outcomes will also include the evaluation of the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) for microbiological treatment monitoring.Discussion: This study will evaluate whether 4-month duration multi-drug treatment including an optimized dose of rifampicin with or without moxifloxacin has non-inferior efficacy and safety outcomes compared to standard of care DS-TB therapy in Africa.

AB - Background: Current combination antibiotic treatment for drug-susceptible tuberculosis (DS-TB) usually takes 6 months to complete. This long duration can compromise clinical outcomes. Although a 4-month regimen including an optimized dose of rifapentine plus moxifloxacin is non-inferior to standard therapy, rifapentine is hard to source globally and adoption of this regimen has been slow. This trial investigates the efficacy and safety of a 4-month DS-TB treatment including the more readily available rifamycin, rifampicin 35 mg/kg, with or without moxifloxacin 400 mg.Methods: This multi-centre phase III randomized open-label clinical trial will be conducted across four African countries (Gabon, Malawi, Mozambique and Tanzania). A total of 414 newly diagnosed consenting adult participants will be block randomized, after stratification by chest radiograph cavitation, to two experimental and one control arm at a ratio of 1:1:1. The first experimental group will receive optimized dose rifampicin (35 mg/kg) with routine weight-banded doses of isoniazid, pyrazinamide, and ethambutol once daily for 4 months. The second experimental group will receive optimized dose rifampicin (35 mg/kg) and moxifloxacin 400 mg once daily alongside routine doses of isoniazid and pyrazinamide. The control group will receive 6-month standard of care therapy: rifampicin (10 mg/kg) plus weight-banded dose of isoniazid, pyrazinamide, and ethambutol for 2 months, followed by the same doses of rifampicin and isoniazid for 4 months. Participants will be followed until the allocation of efficacy (TB-free survival) and safety (proportion of severe adverse events) outcomes. Secondary outcomes will also include the evaluation of the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) for microbiological treatment monitoring.Discussion: This study will evaluate whether 4-month duration multi-drug treatment including an optimized dose of rifampicin with or without moxifloxacin has non-inferior efficacy and safety outcomes compared to standard of care DS-TB therapy in Africa.

KW - Optimized dose rifampicin

KW - Moxifloxacin

KW - Drug susceptible TB

KW - TB-MBLA

U2 - 10.1186/s13063-026-09466-0

DO - 10.1186/s13063-026-09466-0

M3 - Article

C2 - 41612490

SN - 1745-6215

VL - 27

SP - 1

EP - 14

JO - Trials

JF - Trials

M1 - 182

ER -

A pragmatic trial with an optimized dose of rifampicin and moxifloxacin for the treatment of drug-susceptible pulmonary tuberculosis: a study protocol for open-label, randomized phase III trial (OptiRiMoxTB)

Abstract

UN SDGs

Keywords

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SimpliciTB - S Gillespie: EDCTP SimpliciTB 2018

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