Efficacy & Safety of Fluoroquinolone-Based Brucellosis Regimens (BRUCE)

NCT07779629 | Not Yet Recruiting

• 1 other identifier: SHZUBRU20260809
• Study Type: interventional
• Target: 350
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Brucellosis; Osteoarthritis

Keywords

brucellosis; osteoarticular brucellosis; fluoroquinolones; antimicrobial treatment; prospective cohort study

Outcome Measures

Primary Outcomes (5)

• 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.

  End of treatment (Week 6)

• six - month recurrence rate

  The proportion of participants with disease recurrence within 6 months after treatment initiation.

  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%.

  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%.

  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.

  end of treatment (Month 6)

Secondary Outcomes (9)

• 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

Study Arms (6)

Group A without complications

ACTIVE COMPARATOR

Enrolled uncomplicated brucellosis patients, treated with the WHO-recommended dual regimen: oral doxycycline combined with rifampicin for an 8-week course.

Drug: Doxycycline + Rifampicin

Group B without complications

EXPERIMENTAL

Enrolled patients with uncomplicated brucellosis, treated with an 8-week oral dual regimen of doxycycline combined with levofloxacin

Drug: Doxycycline + Levofloxacin

Group C without complications

EXPERIMENTAL

Enrolled patients with uncomplicated brucellosis, treated with an 8-week oral dual regimen of doxycycline combined with moxifloxacin

Drug: Doxycycline + Moxifloxacin

Group A of Brucellosis complicated by osteoarticular complications

ACTIVE COMPARATOR

Enrolled brucellosis patients with osteoarthritic complications, treated with triple therapy combining oral doxycycline, rifampicin and 4-week intravenous ceftriaxone.

Drug: Doxycycline + Rifampicin + Ceftriaxone (intravenous therapy for 4 weeks)

Group B of Brucellosis complicated by osteoarticular complications

EXPERIMENTAL

Enrolled brucellosis patients with osteoarticular complications, treated with an 8-week oral triple regimen: doxycycline + rifampicin + levofloxacin.

Drug: Triple oral regimen (Doxycycline + Rifampicin + Levofloxacin)

Group C of Brucellosis complicated by osteoarticular complications

EXPERIMENTAL

Enrolled patients with uncomplicated brucellosis, treated with an 8-week oral dual regimen of doxycycline combined with moxifloxacin.

Drug: Triple oral regimen (Doxycycline + Rifampicin + Moxifloxacin)

Interventions

Doxycycline + Rifampicin DRUG

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.

Group A without complications

Doxycycline + Levofloxacin DRUG

Experimental dual oral regimen for uncomplicated brucellosis. Patients receive oral doxycycline combined with levofloxacin for a total of 8 weeks.

Group B without complications

Doxycycline + Moxifloxacin DRUG

Experimental dual oral regimen for uncomplicated brucellosis. Patients receive oral doxycycline combined with moxifloxacin for a total of 8 weeks.

Group C without complications

Doxycycline + Rifampicin + Ceftriaxone (intravenous therapy for 4 weeks) DRUG

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.

Group A of Brucellosis complicated by osteoarticular complications

Triple oral regimen (Doxycycline + Rifampicin + Levofloxacin) DRUG

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.

Group B of Brucellosis complicated by osteoarticular complications

Triple oral regimen (Doxycycline + Rifampicin + Moxifloxacin) DRUG

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.

Group C of Brucellosis complicated by osteoarticular complications

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• \. On the basis of the above - mentioned diagnosis of brucellosis, spondylitis and sacroiliitis are also present.

Sponsors & Collaborators

• Xinhua Hospital of Ili Kazakh Autonomous Prefecture, Xinjiang: collaborator
• The Second People's Hospital of Yining, Xinjiang Uyghur Autonomous Region: collaborator
• The First Affiliated Hospital of Shihezi University: lead
• Qitai Hospital of the Sixth Division, Xinjiang Production and Construction Corps: collaborator
• Yanqi Hospital of the Second Division, Xinjiang Production and Construction Corps: collaborator
• Sixth Division Hospital, Xinjiang Production and Construction Corps (Wujiaqu People's Hospital): collaborator

MeSH Terms

Conditions

Brucellosis; Osteoarthritis

Interventions

Doxycycline; Rifampin; Levofloxacin; Moxifloxacin; Ceftriaxone

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Thiazines; Sulfur Compounds

Central Study Contacts

Songsong Xie, MD

CONTACT

+8618999738895; xss2024@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2026
• First Posted: August 21, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 21, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share