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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
350
Standard first-line dual oral regimen recommended by WHO for brucellosis. Eligible patients with uncomplicated brucellosis take oral doxycycline combined with rifampicin continuously for an 8-week course.
Experimental dual oral regimen for uncomplicated brucellosis. Patients receive oral doxycycline combined with levofloxacin for a total of 8 weeks.
Experimental dual oral regimen for uncomplicated brucellosis. Patients receive oral doxycycline combined with moxifloxacin for a total of 8 weeks.
Triple combined regimen for moderate-severe osteoarticular brucellosis. Patients take oral doxycycline and rifampicin continuously, plus 4 weeks of intravenous ceftriaxone infusion. The scheme targets complicated joint and bone lesions to strengthen antibacterial efficacy for severe cases.
Full-course oral triple regimen for brucellosis treatment. Patients continuously take oral doxycycline, rifampicin and levofloxacin for 8 weeks. This regimen boosts antibacterial potency against bone-joint brucellosis lesions and lowers rifampicin resistance risks compared with dual-drug schemes.
Full-course oral triple regimen for brucellosis therapy. Patients take oral doxycycline, rifampicin and moxifloxacin daily for an 8-week treatment cycle. Moxifloxacin delivers outstanding bone-joint tissue penetration, enhancing curative effects for osteoarticular brucellosis and reducing rifampicin resistance risks relative to dual-drug regimens.
clinical cure rate in 6 weeks(body temperature returns to normal, symptoms are relieved)
The proportion of participants achieving clinical cure at 6-week treatment completion, defined as body temperature returning to normal and relief of clinical symptoms.
Time frame: End of treatment (Week 6)
six - month recurrence rate
The proportion of participants with disease recurrence within 6 months after treatment initiation.
Time frame: 6 months after treatment initiation
The time required for the VAS score of joint pain to decrease by ≥50%
The number of days from treatment initiation until the VAS score of joint pain decreases by at least 50%.
Time frame: Baseline (Week0) \During the treatment period (the 3rd month),\end of treatment (Month 6)
Treatment completion rate (compliance rate > 90%)
The proportion of participants who complete the full treatment course with drug compliance greater than 90%.
Time frame: end of treatment (Month 6)
6-month rate of radiological improvement
The proportion of participants with radiological imaging improvement at 6-month end-of-treatment visit.
Time frame: end of treatment (Month 6)
incidence rate of adverse events
The proportion of participants experiencing any adverse event during the observation period.
Time frame: Baseline (Week 0), end of treatment (Week 6), 6 months and 12 months after treatment initiation
incidence rate of serious adverse events (SAE)
The proportion of participants experiencing any serious adverse event (SAE) during the observation period.
Time frame: 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)
The proportion of participants with ALT or AST exceeding 3 times the upper limit of normal.
Time frame: Baseline (Week 0), end of treatment (Week 6), 6 months and 12 months after treatment initiation
Time for body temperature to return to normal
The number of days required for body temperature to return to normal after starting treatment.
Time frame: During treatment (Week 0 to Week 6)
Abnormal renal function (serum creatinine increased by >50%)
The proportion of participants with serum creatinine increased by more than 50% compared with baseline value.
Time frame: Baseline (Week 0), end of treatment (Week 6), 6 months and 12 months after treatment initiation
symptom relief time
The number of days from treatment initiation until clinical symptoms are relieved.
Time frame: During treatment (Week 0 to Week 6)
Quality of life score (SF - 36 scale)
36-Item Short Form Health Survey (SF-36). Scores range from 0 to 100. Higher scores indicate better quality of life.
Time frame: Baseline (Week 0), end of treatment (Week 6), 6 months and 12 months after treatment initiation
Function recovery score (BASDAI score)
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score for assessing joint function recovery.
Time frame: Baseline (Week 0), end of treatment (Week 6), 12 months after treatment initiation
Microbiological cure (Negative conversion of Brucella OMP22 expression)
Microbiological cure defined as negative conversion of Brucella OMP22 expression test.
Time frame: Baseline (Week 0), end of treatment (Week 6), 6 months and 12 months after treatment initiation
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