drugset / Trial / NCT04062201
Building Evidence for Advancing New Treatment for Rifampicin Resistant Tuberculosis (RR-TB) Comparing a Short Course of Treatment (Containing Bedaquiline, Delamanid and Linezolid) With the Current South African Standard of Care
Phase 3
Completed
402 enrolled
Wits Health Consortium (Pty) Ltd
Perinatal HIV Research Unit of the University of the Witswatersrand · collabRegents of the University of California · collabUniversity of Cape Town · collab
RandomizedParallel-groupOpen-labelTreatment
Summary
BEAT Tuberculosis is a phase 3, open label, multi-centre, randomized controlled trial. The purpose of this trial is to compare the efficacy and safety of a Study Strategy consisting of 6 months of bedaquiline (BDQ), delamanid (DLM), and linezolid (LNZ), with levofloxacin (LVX) and clofazimine (CFZ) compared to the current South African Standard of Care (Control Strategy) for 9 months for the treatment of rifampicin resistant (RR-TB) Tuberculosis.
Timeline
- Start
- 2019-08-22
- Primary completion
- 2024-04-15
- Completion
- 2024-04-15
Publications
- Background Diacon AH, Pym A, Grobusch MP, de los Rios JM, Gotuzzo E, Vasilyeva I, Leimane V, Andries K, Bakare N, De Marez T, Haxaire-Theeuwes M, Lounis N, Meyvisch P, De Paepe E, van Heeswijk RP, Dannemann B; TMC207-C208 Study Group. Multidrug-resistant tuberculosis and culture conversion with bedaquiline. N Engl J Med. 2014 Aug 21;371(8):723-32. doi: 10.1056/NEJMoa1313865.
- Background Schnippel K, Ndjeka N, Maartens G, Meintjes G, Master I, Ismail N, Hughes J, Ferreira H, Padanilam X, Romero R, Te Riele J, Conradie F. Effect of bedaquiline on mortality in South African patients with drug-resistant tuberculosis: a retrospective cohort study. Lancet Respir Med. 2018 Sep;6(9):699-706. doi: 10.1016/S2213-2600(18)30235-2. Epub 2018 Jul 11.
- Background Sotgiu G, Centis R, D'Ambrosio L, Alffenaar JW, Anger HA, Caminero JA, Castiglia P, De Lorenzo S, Ferrara G, Koh WJ, Schecter GF, Shim TS, Singla R, Skrahina A, Spanevello A, Udwadia ZF, Villar M, Zampogna E, Zellweger JP, Zumla A, Migliori GB. Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: systematic review and meta-analysis. Eur Respir J. 2012 Dec;40(6):1430-42. doi: 10.1183/09031936.00022912. Epub 2012 Apr 10.
- Background Pym AS, Diacon AH, Tang SJ, Conradie F, Danilovits M, Chuchottaworn C, Vasilyeva I, Andries K, Bakare N, De Marez T, Haxaire-Theeuwes M, Lounis N, Meyvisch P, Van Baelen B, van Heeswijk RP, Dannemann B; TMC207-C209 Study Group. Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis. Eur Respir J. 2016 Feb;47(2):564-74. doi: 10.1183/13993003.00724-2015. Epub 2015 Dec 2.
- Background Drusano GL, Neely M, Van Guilder M, Schumitzky A, Brown D, Fikes S, Peloquin C, Louie A. Analysis of combination drug therapy to develop regimens with shortened duration of treatment for tuberculosis. PLoS One. 2014 Jul 8;9(7):e101311. doi: 10.1371/journal.pone.0101311. eCollection 2014.
- Background Cox H, Ford N. Linezolid for the treatment of complicated drug-resistant tuberculosis: a systematic review and meta-analysis. Int J Tuberc Lung Dis. 2012 Apr;16(4):447-54. doi: 10.5588/ijtld.11.0451.
- Background Briasoulis A, Agarwal V, Pierce WJ. QT prolongation and torsade de pointes induced by fluoroquinolones: infrequent side effects from commonly used medications. Cardiology. 2011;120(2):103-10. doi: 10.1159/000334441. Epub 2011 Dec 13.
- Background Noel GJ, Goodman DB, Chien S, Solanki B, Padmanabhan M, Natarajan J. Measuring the effects of supratherapeutic doses of levofloxacin on healthy volunteers using four methods of QT correction and periodic and continuous ECG recordings. J Clin Pharmacol. 2004 May;44(5):464-73. doi: 10.1177/0091270004264643.
- Background Diacon AH, Dawson R, von Groote-Bidlingmaier F, Symons G, Venter A, Donald PR, van Niekerk C, Everitt D, Hutchings J, Burger DA, Schall R, Mendel CM. Bactericidal activity of pyrazinamide and clofazimine alone and in combinations with pretomanid and bedaquiline. Am J Respir Crit Care Med. 2015 Apr 15;191(8):943-53. doi: 10.1164/rccm.201410-1801OC.
- Background Denti P, Garcia-Prats AJ, Draper HR, Wiesner L, Winckler J, Thee S, Dooley KE, Savic RM, McIlleron HM, Schaaf HS, Hesseling AC. Levofloxacin Population Pharmacokinetics in South African Children Treated for Multidrug-Resistant Tuberculosis. Antimicrob Agents Chemother. 2018 Jan 25;62(2):e01521-17. doi: 10.1128/AAC.01521-17. Print 2018 Feb.
- Background Svensson EM, Dosne AG, Karlsson MO. Population Pharmacokinetics of Bedaquiline and Metabolite M2 in Patients With Drug-Resistant Tuberculosis: The Effect of Time-Varying Weight and Albumin. CPT Pharmacometrics Syst Pharmacol. 2016 Dec;5(12):682-691. doi: 10.1002/psp4.12147. Epub 2016 Nov 8.
- Background Svensson EM, Karlsson MO. Modelling of mycobacterial load reveals bedaquiline's exposure-response relationship in patients with drug-resistant TB. J Antimicrob Chemother. 2017 Dec 1;72(12):3398-3405. doi: 10.1093/jac/dkx317.
- Background Gumbo T, Pasipanodya JG, Wash P, Burger A, McIlleron H. Redefining multidrug-resistant tuberculosis based on clinical response to combination therapy. Antimicrob Agents Chemother. 2014 Oct;58(10):6111-5. doi: 10.1128/AAC.03549-14. Epub 2014 Aug 4.
- Background Chigutsa E, Pasipanodya JG, Visser ME, van Helden PD, Smith PJ, Sirgel FA, Gumbo T, McIlleron H. Impact of nonlinear interactions of pharmacokinetics and MICs on sputum bacillary kill rates as a marker of sterilizing effect in tuberculosis. Antimicrob Agents Chemother. 2015 Jan;59(1):38-45. doi: 10.1128/AAC.03931-14. Epub 2014 Oct 13.
- Conradie F, Badat T, Poswa A, Rajaram S, Kooverjee S, Maartens G, Meintjes G, Hughes J, Schaaf HS, Howell P, Ndjeka N, Phillips PPJ. A Pragmatic Trial of a 6-Month Strategy for Rifampicin-Resistant Tuberculosis. N Engl J Med. 2026 Jun 25;394(24):2429-2439. doi: 10.1056/NEJMoa2503687.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Bedaquiline | Small molecule | 100 mg | Oral |
| Subject | Bedaquiline | Small molecule | 200 mg | Oral |
| Comparator | Clofazimine | Small molecule | 50 mg | Oral |
| Comparator | Clofazimine | Small molecule | 100 mg | Oral |
| Subject | Delamanid | Small molecule | 25 mg | Oral |
| Subject | Delamanid | Small molecule | 50 mg | Oral |
| Subject | Delamanid | Small molecule | 200 mg | Oral |
| Comparator | Ethambutol | Small molecule | 400 mg | Oral |
| Comparator | Ethambutol | Small molecule | 600 mg | Oral |
| Comparator | Ethambutol | Small molecule | 800 mg | Oral |
| Comparator | Ethambutol | Small molecule | 1200 mg | Oral |
| Comparator | Isoniazid | Small molecule | 300 mg | Oral |
| Comparator | Isoniazid | Small molecule | 400 mg | Oral |
| Comparator | Isoniazid | Small molecule | 600 mg | Oral |
| Comparator | Levofloxacin | Small molecule | 375 mg | Oral |
| Comparator | Levofloxacin | Small molecule | 500 mg | Oral |
| Comparator | Levofloxacin | Small molecule | 750 mg | Oral |
| Comparator | Levofloxacin | Small molecule | 1000 mg | Oral |
| Comparator | Linezolid | Other / unclassified | 180 mg | Oral |
| Comparator | Linezolid | Other / unclassified | 210 mg | Oral |
| Comparator | Linezolid | Other / unclassified | 300 mg | Oral |
| Comparator | Linezolid | Other / unclassified | 450 mg | Oral |
| Comparator | Linezolid | Other / unclassified | 600 mg | Oral |
| Comparator | Pyrazinamide | Small molecule | 750 mg | Oral |
| Comparator | Pyrazinamide | Small molecule | 1000 mg | Oral |
| Comparator | Pyrazinamide | Small molecule | 1250 mg | Oral |
| Comparator | Pyrazinamide | Small molecule | 1500 mg | Oral |
| Comparator | Pyrazinamide | Small molecule | 2000 mg | Oral |