Unitat de Tuberculosi Experimental, Germans Trias I Pujol Research Institute (IGTP), Badalona, Catalonia, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
Trials. 2023 Jun 28;24(1):435. doi: 10.1186/s13063-023-07448-0.
The duration and regimen of tuberculosis (TB) treatment is currently based predominantly on whether the M. tuberculosis (Mtb) strain is drug-sensitive (DS) or multidrug-resistant (MDR) with doses adjusted by patients' weight only. The systematic stratification of patients for personalized treatment does not exist for TB. As each TB case is different, individualized treatment regimens should be applied to obtain better outcomes. In this scenario, novel therapeutic approaches are urgently needed to (1) improve outcomes and (2) shorten treatment duration, and host-directed therapies (HDT) might be the best solution. Within HDT, repurposed drugs represent a shortcut in drug development and can be implemented at the short term. As hyperinflammation is associated with worse outcomes, HDT with an anti-inflammatory effect might improve outcomes by reducing tissue damage and thus the risk of permanent sequelae.
SMA-TB is a multicentre randomized, phase IIB, placebo-controlled, three-arm, double-blinded clinical trial (CT) that has been designed in the context of the EC-funded SMA-TB Project ( www.smatb.eu ) in which we propose to use 2 common non-steroidal anti-inflammatory drugs (NSAID), acetylsalicylic acid (ASA) and ibuprofen (Ibu), as an HDT for use as adjunct therapy added to, and compared with, the standard of care (SoC) World Health Organization (WHO)-recommended TB regimen in TB patients. A total of 354 South African and Georgian adults diagnosed with confirmed pulmonary TB will be randomized into SoC TB treatment + placebo, SoC + acetylsalicylic acid or SoC + ibuprofen.
SMA-TB will provide proof of concept of the HDT as a co-adjuvant treatment and identify the suitability of the intervention for different population groups (different epidemiological settings and drug susceptibility) in the reduction of tissue damage and risk of bad outcomes for TB patients. This regimen potentially will be more effective and targeted: organ saving, reducing tissue damage and thereby decreasing the length of treatment and sequelae, increasing cure rates and pathogen clearance and decreasing transmission rates. It will result in better clinical practice, care management and increased well-being of TB patients.
Clinicaltrials.gov NCT04575519. Registered on October 5, 2020.
目前结核病（TB）的治疗持续时间和方案主要取决于结核分枝杆菌（Mtb）菌株是药敏（DS）还是耐多药（MDR），剂量仅根据患者体重调整。针对 TB 患者的系统性分层治疗尚未实现。由于每个 TB 病例都不同，因此应应用个体化治疗方案以获得更好的结果。在这种情况下，迫切需要新的治疗方法来：（1）改善结果，（2）缩短治疗时间，而宿主导向治疗（HDT）可能是最佳解决方案。在 HDT 中，重新定位的药物代表了药物开发的捷径，可以在短期内实施。由于过度炎症与更差的结果相关，因此具有抗炎作用的 HDT 可能通过减少组织损伤从而降低永久性后遗症的风险来改善结果。
SMA-TB 是一项多中心随机、IIb 期、安慰剂对照、三臂、双盲临床试验（CT），是在欧盟资助的 SMA-TB 项目（www.smatb.eu）的背景下设计的，我们建议在这项研究中使用两种常见的非甾体抗炎药（NSAID），即乙酰水杨酸（ASA）和布洛芬（Ibu），作为 HDT，作为附加治疗，与世卫组织推荐的结核病标准治疗（SoC）方案进行比较，治疗结核病患者。共有 354 名南非和格鲁吉亚成年人被诊断为确诊的肺结核，将随机分为 SoC 结核病治疗+安慰剂、SoC+乙酰水杨酸或 SoC+布洛芬。
SMA-TB 将提供宿主导向治疗作为辅助治疗的概念验证，并确定干预措施在减少组织损伤和结核病患者不良结局风险方面对不同人群（不同的流行病学环境和药物敏感性）的适用性。这种方案可能更有效和有针对性：保存器官，减少组织损伤，从而缩短治疗时间和后遗症，提高治愈率和病原体清除率，降低传播率。它将带来更好的临床实践、护理管理和增加结核病患者的幸福感。
Clinicaltrials.gov NCT04575519。于 2020 年 10 月 5 日注册。
