Two-month Regimens Using Novel Combinations to Augment Treatment Effectiveness for Drug-sensitive Tuberculosis

Summary

The current standard management strategy for drug-sensitive pulmonary tuberculosis (TB) is to treat with multiple drugs for 6 months, although patients often fail to adhere to the long treatment, leading to poor clinical outcomes including drug resistance, which is expensive and difficult to treat. The TRUNCATE-TB trial evaluates an alternative strategy (the TRUNCATE-TB Management Strategy) comprising treatment for 2 months (8 weeks, extended to 12 weeks if inadequate clinical response) with a regimen predicted to have enhanced sterilising activity ("boosted regimen") and monitoring closely after treatment cessation. Those who relapse (predicted to be always drug sensitive and likely to occur early) will be retreated with a standard 6 month regimen. The trial is a randomized, open-label, multi-arm, multi-stage (MAMS) trial to test the hypothesis that the TRUNCATE-TB Management Strategy is non-inferior to the standard management strategy in terms of longer-term outcomes (clinical status at 96 weeks). If non-inferiority is demonstrated then the advantages/disadvantages of implementing the strategy will be explored in secondary outcomes (from patient and programme perspective). The trial will evaluate the TRUNCATE-TB Management Strategy with 4 potential boosted regimens (180 per arm, total 900 with the standard TB management strategy arm). The boosted regimens include new drugs (licensed drugs, repurposed from other indications) and optimized doses of standard drugs, selected based on consideration of maximal sterilising effect, absence of drug-drug interactions, as well as safety and tolerability over a period of 2 months

Timeline

Start

2018-03-21

Primary completion

2022-01-20

Completion

2022-01-20

Publications

• Paton NI, Cousins C, Sari IP, Burhan E, Ng NK, Dalay VB, Suresh C, Kusmiati T, Chew KL, Balanag VM, Lu Q, Ruslami R, Djaharuddin I, Sugiri JJR, Veto RS, Sekaggya-Wiltshire C, Avihingsanon A, Saini JK, Papineni P, Nunn AJ, Crook AM; TRUNCATE-TB Trial Team. Efficacy and safety of 8-week regimens for the treatment of rifampicin-susceptible pulmonary tuberculosis (TRUNCATE-TB): a prespecified exploratory analysis of a multi-arm, multi-stage, open-label, randomised controlled trial. Lancet Infect Dis. 2025 Oct;25(10):1084-1096. doi: 10.1016/S1473-3099(25)00151-3. Epub 2025 May 22.
• Paton NI, Cousins C, Suresh C, Burhan E, Chew KL, Dalay VB, Lu Q, Kusmiati T, Balanag VM, Lee SL, Ruslami R, Pokharkar Y, Djaharuddin I, Sugiri JJR, Veto RS, Sekaggya-Wiltshire C, Avihingsanon A, Sarin R, Papineni P, Nunn AJ, Crook AM; TRUNCATE-TB Trial Team. Treatment Strategy for Rifampin-Susceptible Tuberculosis. N Engl J Med. 2023 Mar 9;388(10):873-887. doi: 10.1056/NEJMoa2212537. Epub 2023 Feb 20.
• Converse PJ, Almeida DV, Tasneen R, Saini V, Tyagi S, Ammerman NC, Li SY, Anders NM, Rudek MA, Grosset JH, Nuermberger EL. Shorter-course treatment for Mycobacterium ulcerans disease with high-dose rifamycins and clofazimine in a mouse model of Buruli ulcer. PLoS Negl Trop Dis. 2018 Aug 13;12(8):e0006728. doi: 10.1371/journal.pntd.0006728. eCollection 2018 Aug.

Drugs

Indications