Author:
Feng Zhen,Miao Yan,Peng Ying,Sun Feng,Zhang Yilin,Li Rong,Ge Shijia,Chen Xinchang,Song Lingyun,Li Yang,Wang Xiaomeng,Zhang Wenhong
Abstract
Abstract
Background
Standard treatment for drug-susceptible tuberculosis (DS-TB) includes a multidrug regimen requiring at least 6 months of treatment, and this lengthy treatment easily leads to poor adherence. There is an urgent need to simplify and shorten treatment regimens to reduce interruption and adverse event rates, improve compliance, and reduce costs.
Methods
ORIENT is a multicenter, randomized controlled, open-label, phase II/III, non-inferiority trial involving DS-TB patients to evaluate the safety and efficacy of short-term regimens compared with the standardized six-month treatment regimen. In stage 1, corresponding to a phase II trial, a total of 400 patients are randomly divided into four arms, stratified by site and the presence of lung cavitation. Investigational arms include 3 short-term regimens with rifapentine 10 mg/kg, 15 mg/kg, and 20 mg/kg, while the control arm uses the standardized six-month treatment regimen. A combination of rifapentine, isoniazid, pyrazinamide, and moxifloxacin is administered for 17 or 26 weeks in rifapentine arms, while a 26-week regimen containing rifampicin, isoniazid, pyrazinamide, and ethambutol is applied in the control arm. After the safety and preliminary effectiveness analysis of patients in stage 1, the control arm and the investigational arm meeting the conditions will enter into stage 2, which is equivalent to a phase III trial and will be expanded to recruit DS-TB patients. If all investigational arms do not meet the safety conditions, stage 2 will be canceled. In stage 1, the primary safety endpoint is permanent regimen discontinuation at 8 weeks after the first dose. The primary efficacy endpoint is the proportion of favorable outcomes at 78 weeks after the first dose for both two stages.
Discussion
This trial will contribute to the optimal dose of rifapentine in the Chinese population and suggest the feasibility of the short-course treatment regimen containing high-dose rifapentine and moxifloxacin for DS-TB.
Trial registration
The trial has been registered on ClinicalTrials.gov on 28 May 2022 with the identifier NCT05401071.
Funder
National Natural Science Foundation of China
Shanghai Municipal Science and Technology Major Project
Shanghai Science and Technology Committee
Publisher
Springer Science and Business Media LLC
Reference38 articles.
1. WHO. Global Tuberculosis Report 2022. Geneva: World Health Organization; 2022 https://www.who.int/publications/i/item/9789240061729. Accessed 13 Mar 2023.
2. WHO. WHO Operational Handbook on Tuberculosis, Module 4: Treatment - Drug-Susceptible Tuberculosis Treatment. Geneva: World Health Organization; 2020. https://apps.who.int/iris/rest/bitstreams/1421257/retrieve. Accessed 13 Mar 2023.
3. Imperial MZ, Nahid P, Phillips PPJ, Davies GR, Fielding K, Hanna D, et al. A patient-level pooled analysis of treatment-shortening regimens for drug-susceptible pulmonary tuberculosis. Nat Med. 2018;24(11):1708–15.
4. Alipanah N, Jarlsberg L, Miller C, Linh NN, Falzon D, Jaramillo E, et al. Adherence interventions and outcomes of tuberculosis treatment: A systematic review and meta-analysis of trials and observational studies. PLoS Med. 2018;15(7):e1002595.
5. Fox W, Ellard GA, Mitchison DA. Studies on the treatment of tuberculosis undertaken by the British Medical Research Council tuberculosis units, 1946–1986, with relevant subsequent publications. Int J Tuberc Lung Dis. 1999;3(10 Suppl 2):S231–79.