A Prospective, Multicenter, Randomized, Open-Label, Parallel-Group Clinical Trial: Efficacy and Safety of Fluoroquinolone-Based Regimens for Uncomplicated and Osteoarticular Brucellosis (the BRUCE Study)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 350
- 主要终点
- clinical cure rate in 6 weeks(body temperature returns to normal, symptoms are relieved)
研究概览
简要总结
Brucellosis is a globally distributed zoonosis with persistent clinical management challenges. The World Health Organization(WHO)-recommended doxycycline-rifampin (DOX-RIF) dual regimen may drive rifampin-associated antimicrobial resistance across all brucellosis-endemic regions. Patients with osteoarticular brucellosis require long-term intravenous ceftriaxone triple therapy, which is linked to poor treatment adherence due to repeated hospital visits and outpatient care demands. Fluoroquinolones (levofloxacin [LVX], moxifloxacin [MXF]) exert excellent anti-Brucella activity and superior bone-joint penetration, yet high-quality multicenter prospective data comparing rifampin-sparing LVX-DOX/MXF-DOX dual regimens against standard RIF-DOX remain rarely reported. Existing comparative studies are limited to small single-center retrospective cohorts or trials pairing rifampin with fluoroquinolones rather than rifampin-free dual oral therapy. This multicenter prospective parallel-cohort protocol includes Module I (non-inferiority design) : 200 patients with uncomplicated acute brucellosis receiving 6-week dual oral therapy; and Module II (non-inferiority design) : 150 patients with imaging-confirmed osteoarticular brucellosis receiving 12-week triple therapy. Clinical data of standardized clinical, laboratory, radiologic, and subsequent longitudinal follow-up data will be collected via centralized electronic data capture. Primary endpoints include clinical and microbiological cure rates at 6 weeks (Module I) and 12 weeks (Module II). Secondary endpoints measure 24-week post treatment recurrence, 24- and 48-week radiologic improvement for osteoarticular disease, and adverse events during treatment. Multivariate regression and Cox models will identify independent prognostic factors and construct a generalizable recurrence risk prediction model. This clinical trial fills a critical evidence gap for oral fluoroquinolone-based regimens, with findings intended to supply supplementary brucellosis treatment approach, reduce rifampin resistance pressure, and eliminate reliance on prolonged parenteral therapy for complicated brucellosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The diagnostic basis for confirmed cases of brucellosis is the "Expert Consensus on the Diagnosis and Treatment of Brucellosis" published by the Editorial Board of the Chinese Journal of Infectious Diseases in 2017 and the "Diagnosis and Treatment Protocol for Brucellosis (2023 Edition)".
- •There is an epidemiological history, such as a history of contact with suspected or confirmed animals, patients, contaminated animal products, or cultures; living in an endemic area of brucellosis; or having a close relationship with the production, use, and research of vaccines.
- •At the same time, there are the following relevant clinical manifestations: fever, hyperhidrosis, joint pain, headache, fatigue, anorexia, myalgia, weight loss, arthritis, spondylitis, meningitis, or focal organ involvement such as endocarditis, hepatosplenomegaly, orchitis, or epididymitis.
- •In the serological screening, the Rose Bengal plate agglutination test is positive. For the tube agglutination test (SAT), the titer is 1:100 or higher with significant agglutination, or if the course of the disease is more than one year, the titer is 1:50 with significant agglutination or higher; or if there is a history of brucellosis vaccination within half a year, the titer reaches 1:100 with significant agglutination or higher. Accompanied by (or) positive culture of Brucella in the patient's blood, body fluids, or tissues. Or positive NGS detection of Brucella.
- •2. On the basis of the above - mentioned diagnosis of brucellosis, spondylitis and sacroiliitis are also present.
排除标准
- •Those with comorbid tuberculosis, severe cardiopulmonary dysfunction, advanced tumors, central nervous system diseases (such as a history of epilepsy), or other systemic diseases;
- •Those with comorbid neurological or mental disorders who are unable or unwilling to cooperate;
- •Pregnant or lactating women, or those with a recent plan to have children;
- •Patients with a history of using glucocorticoids, immunomodulators, anti - tuberculosis drugs, etc. within the past 3 months;
- •Patients with missing important information or abnormal mental states.
研究组 & 干预措施
Group A without complications
Enrolled uncomplicated brucellosis patients, treated with the WHO-recommended dual regimen: oral doxycycline combined with rifampicin for an 8-week course.
干预措施: Doxycycline + Rifampicin (Drug)
Group B without complications
Enrolled patients with uncomplicated brucellosis, treated with an 8-week oral dual regimen of doxycycline combined with levofloxacin
干预措施: Doxycycline + Levofloxacin (Drug)
Group C without complications
Enrolled patients with uncomplicated brucellosis, treated with an 8-week oral dual regimen of doxycycline combined with moxifloxacin
干预措施: Doxycycline + Moxifloxacin (Drug)
Group A of Brucellosis complicated by osteoarticular complications
Enrolled brucellosis patients with osteoarthritic complications, treated with triple therapy combining oral doxycycline, rifampicin and 4-week intravenous ceftriaxone.
干预措施: Doxycycline + Rifampicin + Ceftriaxone (intravenous therapy for 4 weeks) (Drug)
Group B of Brucellosis complicated by osteoarticular complications
Enrolled brucellosis patients with osteoarticular complications, treated with an 8-week oral triple regimen: doxycycline + rifampicin + levofloxacin.
干预措施: Triple oral regimen (Doxycycline + Rifampicin + Levofloxacin) (Drug)
Group C of Brucellosis complicated by osteoarticular complications
Enrolled patients with uncomplicated brucellosis, treated with an 8-week oral dual regimen of doxycycline combined with moxifloxacin.
干预措施: Triple oral regimen (Doxycycline + Rifampicin + Moxifloxacin) (Drug)
结局指标
主要结局
clinical cure rate in 6 weeks(body temperature returns to normal, symptoms are relieved)
时间窗: End of treatment (Week 6)
The proportion of participants achieving clinical cure at 6-week treatment completion, defined as body temperature returning to normal and relief of clinical symptoms.
six - month recurrence rate
时间窗: 6 months after treatment initiation
The proportion of participants with disease recurrence within 6 months after treatment initiation.
The time required for the VAS score of joint pain to decrease by ≥50%
时间窗: Baseline (Week0) \During the treatment period (the 3rd month),\end of treatment (Month 6)
The number of days from treatment initiation until the VAS score of joint pain decreases by at least 50%.
Treatment completion rate (compliance rate > 90%)
时间窗: end of treatment (Month 6)
The proportion of participants who complete the full treatment course with drug compliance greater than 90%.
6-month rate of radiological improvement
时间窗: end of treatment (Month 6)
The proportion of participants with radiological imaging improvement at 6-month end-of-treatment visit.
次要结局
- incidence rate of adverse events(Baseline (Week 0), end of treatment (Week 6), 6 months and 12 months after treatment initiation)
- incidence rate of serious adverse events (SAE)(Baseline (Week 0), end of treatment (Week 6), 6 months and 12 months after treatment initiation)
- abnormal liver function (ALT/AST >3 times the normal value)(Baseline (Week 0), end of treatment (Week 6), 6 months and 12 months after treatment initiation)
- Time for body temperature to return to normal(During treatment (Week 0 to Week 6))
- Abnormal renal function (serum creatinine increased by >50%)(Baseline (Week 0), end of treatment (Week 6), 6 months and 12 months after treatment initiation)
- symptom relief time(During treatment (Week 0 to Week 6))
- Quality of life score (SF - 36 scale)(Baseline (Week 0), end of treatment (Week 6), 6 months and 12 months after treatment initiation)
- Function recovery score (BASDAI score)(Baseline (Week 0), end of treatment (Week 6), 12 months after treatment initiation)
- Microbiological cure (Negative conversion of Brucella OMP22 expression)(Baseline (Week 0), end of treatment (Week 6), 6 months and 12 months after treatment initiation)