Trials Data Summary

Standard Treatment Regimen of Anti-tuberculosis Drugs for Patients With MDR-TB (STREAM stage 1 and 2)

N Observations: 424 and 588

Acknowledgement: STREAM Stage 1 was funded by the United States Agency for International Development (USAID) through the Cooperative Agreement GHN-A-00-08-0004-00. Stage 2 of STREAM was jointly funded by USAID and Janssen Research & Development, LLC. Additional funding for STREAM was provided by the Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement which is also part of the EDCTP2 programme supported by the European Union. The MRC Clinical Trials Unit at University College London was supported by the MRC (MC_UU_00004/04). We thank all the participants and collaborators without whom the STREAM study would not have been possible.

Reference:

• Nunn AJ, Phillips PP, Meredith SK, et al. A trial of a shorter regimen for rifampin-resistant tuberculosis. N Engl J Med. 2019;380(13):1201-1213.

• Goodall RL, Meredith SK, Nunn AJ, et al. Evaluation of two short standardised regimens for the treatment of rifampicin-resistant tuberculosis (STREAM stage 2): an open-label, multicentre, randomised, non-inferiority trial. The Lancet. 2022;400(10366):1858-1868.

   

A randomised, controlled, open-label, phase II–III trial to evaluate the safety and efficacy of regimens containing bedaquiline and pretomanid for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis (TB-PRACTECAL)

N Observations: 552

Acknowledgement: Médecins Sans Frontiers, all TB-PRACTECAL partners and all the patients who gave their data

Reference:

• Nyang’wa B-T, Berry C, Kazounis E et al. Short oral regimens for pulmonary rifampicin-resistant tuberculosis (TB-PRACTECAL): an open-label, randomised, controlled, phase 2B-3, multi-arm, multicentre, non-inferiority trial. Lancet Respir Med 2023. https://doi.org/10.1016/S2213-2600(23)00389-2

• Nyang’wa B-T, Berry C, Kazounis E, et al. A 24-week, all-oralregimen for rifampin-resistant tuberculosis. N Engl J Med 2022; 387: 2331–43. https://doi.org/10.1056/NEJMoa2117166

   

9 months of delamanid, linezolid, levofloxacin, and pyrazinamide versus conventional therapy for treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-END)

N Observations: 214

Acknowledgement: Jae-Joon Yim, M.D., Jeongha Mok, M.D., and Young Ran Kim, RN

Reference:

• Mok J, Lee M, Kim DK, Kim JS, Jhun BW, et al; MDR-END investigators. 9 months of delamanid, linezolid, levofloxacin, and pyrazinamide versus conventional therapy for treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-END): a multicentre, randomised, open-label phase 2/3 non-inferiority trial in South Korea. Lancet. 2022 Oct 29;400(10362):1522-1530. doi: 10.1016/S0140-6736(22)01883-9. PMID: 36522208.

• Lee M, Mok J, Kim DK, Shim TS, Koh WJ, et al. Delamanid, linezolid, levofloxacin, and pyrazinamide for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (Treatment Shortening of MDR-TB Using Existing and New Drugs, MDR-END): study protocol for a phase II/III, multicenter, randomized, open-label clinical trial. Trials. 2019 Jan 16;20(1):57. doi: 10.1186/s13063-018-3053-1. PMID: 30651149; PMCID: PMC6335682.

   

Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis (RIFASHORT)

N Observations: 672

Acknowledgement: Amina Jindani, Daniel Atwine, Daniel Grint, Boubacar Bah, Jack Adams, Eduardo Rómulo Ticona, Bhabana Shrestha, Tefera Agizew, Saeed Hamid, Bushra Jamil, Adolf Byamukama, Keneth Kananura, Ivan Mugisha Taremwa, Maryline Bonnet, Lansana Mady Camara, Oumou Younoussa Bah-Sow, Kindy Sadjo Bah Nene Mamata Bah, Maimouna Sow, César Eduardo Ticona Huaroto, Raquel Mugruza Pineda, Bijesh Tandukar, Bijendra Bhakta Raya, Neko Shrestha, Anikie Mathoma, Unami P. Mathebula- Modongo , Joyce Basotli, Muhammad Irfan, Dilshad Begum, Ammara Muzammil, Marcos V Burgos, Faisal Sultan, Mariam Hassan, Iqra Masood, Claire Robb, Jonathan Decker, Sisa Grubnic, Philip D. Butcher, Adam Whitney, Jasvir Dhillon, Tulika Munshi, Katherine Fielding, and Thomas S Harrison, on behalf of The Rifashort Study Group. Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis. Medical Research Council/Wellcome Trust/DFID Global Health Trials Scheme

Reference: Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis NEJM Evidence 2023. DOI: 10.1056.

A randomised Phase II trial to evaluate the toxicity of high-dose rifampicin to treat pulmonary tuberculosis (RIFATOX)

N Observations: 300

Acknowledgement: St. George’s, University of London. A. Jindani, G. Borgulya, I. Westermann de Patiño, T. Gonzales, R. A. de Fernandes, B. Shrestha, D. Atwine, M. Bonnet, M. Burgos, F. Dubash, N. Patel, A. M. Checkley, T. S. Harrison, D. Mitchison, International Consortium for Trials of Chemotherapeutic Agents in Tuberculosis, St George’s, University of London. A randomised Phase II trial to evaluate the toxicity of high-dose rifampicin to treat pulmonary tuberculosis(The RIFATOX Trial).

Reference: A randomised Phase II trial to evaluate the toxicity of high-dose rifampicin to treat pulmonary tuberculosis. Int J Tuberc Lung Dis . 2016 Jun;20(6):832-8. doi: 10.5588/ijtld.15.0577

A multicentre randomised controlled clinical trial to evaluate high dose rifapentine and a quinolone in the treatment of pulmonary tuberculosis (RIFAQUIN)

N Observations: 827

Acknowledgement: Amina Jindani, Tom S. Harison, Andrew J. Nunn, Patrick P J Phillips, Philip Butcher, Denny Mitchison. European and Developing Countries Clinical Trials Partnership

Reference: High-Dose Rifapentine with Moxifloxacin for Pulmonary Tuberculosis. New England Journal of Medicine:.2014, 371(17):1599-1608

Shorter Treatment for Nonsevere Tuberculosis in African and Indian Children (SHINE)

N Observations: 1204

Acknowledgement: SHINE trial team and SHINE study participants. Trial supported by a grant (MR/L004445/1) from the U.K. Medical Research Council (MRC) and the Department for International Development (DFID) Wellcome NIHR Joint Global Health Trials, by a U.K. Research and Innovation Covid-19 Grant Extension Allocation Award, by a U.K. Research and Innovation MRC grant (MC_UU_00004/04), and by a Clinician Scientist Fellowship, jointly funded by the MRC and the Department for International Development under an MRC–DFID Concordat agreement (MR/R007942/1). TB Alliance provided support for drug purchase.

Reference: Turkova A, Wills GH, Wobudeya E, Chabala C, Palmer M, Kinikar A, Hissar S, Choo L, Musoke P, Mulenga V, Mave V. Shorter treatment for nonsevere tuberculosis in African and Indian children. New England Journal of Medicine. 2022 Mar 10;386(10):911-22.

BEAT-TB

N Observations: 402

Acknowledgement: Dr Francesca Conradie, USAID

Reference: Manuscript in preparation