Study protocol for safety and efficacy of all-oral shortened regimens for multidrug-resistant tuberculosis: a multicenter randomized withdrawal trial and a single-arm trial [SEAL-MDR]

Fu，Liang1; Xiong，Juan2; Wang，Haibo3; Zhang，Peize1; Yang，Qianting1; Cai，Yi4; Wang，Wenfei1,4; Sun，Feng5; Zhang，Xilin6; Wang，Zhaoqin1; Chen，Xinchun4; Zhang，Wenhong5; Deng，Guofang1

2023-12-01

10.1186/s12879-023-08644-8

BMC Infectious Diseases   影响因子和分区

1471-2334

Introduction: The urgent need for new treatments for multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is evident. However, the classic randomized controlled trial (RCT) approach faces ethical and practical constraints, making alternative research designs and treatment strategies necessary, such as single-arm trials and host-directed therapies (HDTs). Methods: Our study adopts a randomized withdrawal trial design for MDR-TB to maximize resource allocation and better mimic real-world conditions. Patients’ treatment regimens are initially based on drug resistance profiles and patient’s preference, and later, treatment-responsive cases are randomized to different treatment durations. Alongside, a single-arm trial is being conducted to evaluate the potential of sulfasalazine (SASP) as an HDT for pre-XDR-TB, as well as another short-course regimen without HDT for pre-XDR-TB. Both approaches account for the limitations in second-line anti-TB drug resistance testing in various regions. Discussion: Although our study designs may lack the internal validity commonly associated with RCTs, they offer advantages in external validity, feasibility, and ethical appropriateness. These designs align with real-world clinical settings and also open doors for exploring alternative treatments like SASP for tackling drug-resistant TB forms. Ultimately, our research aims to strike a balance between scientific rigor and practical utility, offering valuable insights into treating MDR-TB and pre-XDR-TB in a challenging global health landscape. In summary, our study employs innovative trial designs and treatment strategies to address the complexities of treating drug-resistant TB, fulfilling a critical gap between ideal clinical trials and the reality of constrained resources and ethical considerations. Trail registration: Chictr.org.cn, ChiCTR2100045930. Registered on April 29, 2021.

Efficacy Multidrug-resistant Safety Trial Tuberculosis

SCI

英语

第一 ; 通讯

WOS:001114809300002

IMMUNOLOGY

2-s2.0-85178052099

Scopus

1.Division Two of Pulmonary Diseases Department,Shenzhen Third People’s Hospital,Shenzhen Clinical Research Center for Tuberculosis,National Clinical Research Center for Infectious Disease (Shenzhen),Southern University of Science and Technology,Shenzhen,29 Bulan Rd, Longgang District,518112,China
2.Health Science Center,Shenzhen University,Shenzhen,3688 Nanhai Avenue, Nanshan District,518060,China
3.Peking University Clinical Research Institute,Peking University First Hospital,Beijing,Xueyuan Rd 38#, Haidian District,100000, 100191,China
4.Department of Pathogen Biology,Guangdong Key Laboratory of Regional Immunity and Diseases,Shenzhen University School of Medicine,Shenzhen,1066 Xueyuan Ave, Nanshan District,518060,China
5.Department of Infectious Diseases,Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response,National Medical Center for Infectious Diseases,Huashan Hospital,Fudan University,Shanghai,12 Urumqi Middle Road, Jing’an District,200040,China
6.Tuberculosis Prevention and Control Department,The Fourth People’s Hospital of Foshan,Foshan,106 Jinlannan Rd, Chancheng District,528000,China

Fu，Liang,Xiong，Juan,Wang，Haibo,et al. Study protocol for safety and efficacy of all-oral shortened regimens for multidrug-resistant tuberculosis: a multicenter randomized withdrawal trial and a single-arm trial [SEAL-MDR][J]. BMC Infectious Diseases,2023,23(1).

Fu，Liang.,Xiong，Juan.,Wang，Haibo.,Zhang，Peize.,Yang，Qianting.,...&Deng，Guofang.(2023).Study protocol for safety and efficacy of all-oral shortened regimens for multidrug-resistant tuberculosis: a multicenter randomized withdrawal trial and a single-arm trial [SEAL-MDR].BMC Infectious Diseases,23(1).

Fu，Liang,et al."Study protocol for safety and efficacy of all-oral shortened regimens for multidrug-resistant tuberculosis: a multicenter randomized withdrawal trial and a single-arm trial [SEAL-MDR]".BMC Infectious Diseases 23.1(2023).