Rifapentine-and moxifloxacin-containing short-course regimens for mild spinal tuberculosis: study protocol for a multicenter, randomized, non-inferiority phase II clinical trial

Yue-E Wu¹Jing Cao¹Li Wang²Ying-Ji Wei³Hui-Xin Liu¹Lei Qi⁴Wen Zhang⁵Feng Liu⁶Zhong-Jiao Zhu⁷Xu-Tao Fan⁸Sheng Wang⁹Cong Chen¹⁰Xiang-Ze Liu¹¹Ying Li¹²Zhong-Zheng Sun¹³Jing-Bo Pan¹⁴Chao-Qun Yang¹⁵Johannes Nicolaas Van Den Anker¹Qiang Zhang^2*Wei Zhao^1*

• ¹Shandong University, Jinan, China
• ²Shandong Public Health Clinical Center, Jinan, China
• ³Linyi Mental Health Center, Linyi, China
• ⁴Qilu Hospital of Shandong University, Jinan, China
• ⁵Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
• ⁶Taian City Central Hospital, Tai'an, China
• ⁷Tengzhou Central People's Hospital, Shandong, China
• ⁸Affiliated Hospital of Jining Medical University, Jining, China
• ⁹Affiliated Hospital of Shandong Second Medical University, Weifang, China
• ¹⁰Weihai Municipal Hospital, Weihai, China
• ¹¹Weifang NO.2 People's Hospital, Weifang, China
• ¹²Zibo Infectious Diseases Hospital, Zibo, China
• ¹³PKUCare Luzhong Hospital, Zibo, China
• ¹⁴Yantaishan Hospital Affiliated to Binzhou Medical University, Yantai, China
• ¹⁵Jinan Third People's Hospital, Jinan, China

Background Spinal tuberculosis is the most common form of osteoarticular infection, with recommended anti-tuberculosis treatment durations typically being long (9-18 months), even for mild cases, increasing the risks of drug resistance, toxicity, and poor patient adherence. This study aims to explore, in patients with mild spinal tuberculosis, whether a new combination of anti-tuberculosis drugs (containing rifapentine and moxifloxacin) could shorten the treatment duration. Methods and Analysis This trial is an open-label, randomized, controlled, non-inferiority trial comparing the efficacy and safety of a short-course regimen [6-month anti-TB regimen] containing rifapentine and moxifloxacin with empirical long-course regimen [12-month anti-TB regimen] in the treatment of patients with mild spinal tuberculosis. Patients diagnosed with mild spinal tuberculosis who meet the inclusion and exclusion criteria will be recruited and randomized in a 1:1 ratio to either of the two arms. Empirical long-course regimen includes rifampin, isoniazid, pyrazinamide and ethambutol (2RHZE/10RH), while short-course regimen includes rifapentine, moxifloxacin, isoniazid and pyrazinamide (2HRtZM/4HRtM). The primary endpoint is TB-recurrence rate at 24 months after completion of treatment and proportion of participants with grade 3 or higher adverse events during treatment with study medications. Discussion This trial will provide evidence whether a short-course regimen of anti-TB drugs (2HRtZM/4HRtM) is non-inferior to the empirical long-course regimen (2RHZE/10RH) in patients with mild spinal tuberculosis. If non-inferiority is established, it will contribute to a more optimized treatment for spinal tuberculosis. Trials Registration NCT06917495. Registered on 7 April 2025. https://clinicaltrials.gov/ct2/show/NCT06917495.