A Multicenter, Randomized, Controlled Trial Evaluating the Efficacy and Safety of Adding Fluoroquinolone (Levofloxacin or Moxifloxacin) to Standard Triple Therapy in Disseminated Mycobacterium Avium Complex Infection
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 124
研究概览
简要总结
Background:
Disseminated Mycobacterium avium complex (MAC) infection remains a serious opportunistic infection in patients with advanced HIV infection, particularly among those with severe immunosuppression. Despite the widespread use of antiretroviral therapy (ART), disseminated MAC (DMAC) continues to be associated with significant morbidity and mortality. The current standard treatment consists of a macrolide-based triple regimen, including a macrolide, ethambutol, and rifamycin. However, in patients with high mycobacterial burden or profound immunodeficiency, early microbiological response and clinical improvement are often suboptimal, and treatment is complicated by drug interactions and tolerability issues.
Objective:
This study aims to evaluate whether adding a fluoroquinolone (levofloxacin or moxifloxacin) to the standard triple therapy improves early clinical outcomes in HIV-infected patients with disseminated MAC infection.
Methods:
This is a prospective, multicenter, randomized, open-label, controlled trial. A total of 124 adult HIV-infected patients with confirmed disseminated MAC infection will be randomly assigned in a 1:1 ratio to receive either standard triple therapy (macrolide, ethambutol, and rifamycin) or an intensified four-drug regimen with the addition of a fluoroquinolone during the initial 8-week intensive phase. Participants will be followed for at least 24 weeks.
Outcomes:
The primary endpoint is the clinical symptom resolution rate at Day 28. Secondary endpoints include microbiological outcomes (culture or molecular conversion at Days 28, 56, and 84), time to culture conversion, mortality, relapse, and safety outcomes including adverse events and QT interval prolongation.
Significance:
This study will provide prospective evidence on whether an intensified treatment strategy can improve early clinical response and microbiological clearance in disseminated MAC infection, while maintaining an acceptable safety profile. The findings may help optimize treatment strategies for HIV-associated disseminated MAC infection.
详细描述
Background and Rationale:
Disseminated Mycobacterium avium complex (MAC) infection remains a major opportunistic infection in patients with advanced HIV infection, particularly among those with severe immunosuppression (e.g., CD4 <50 cells/μL). Although the incidence of disseminated MAC (DMAC) has declined in the era of antiretroviral therapy (ART), it continues to pose a substantial clinical burden due to delayed diagnosis, high mycobacterial load, and frequent co-infections. Clinically, DMAC often presents with systemic symptoms such as fever, weight loss, anemia, and multi-organ involvement, including bone marrow, liver, spleen, and lymph nodes.
Current guidelines recommend a macrolide-based triple therapy consisting of a macrolide (azithromycin or clarithromycin), ethambutol, and a rifamycin (typically rifabutin). This regimen has demonstrated efficacy in reducing mortality and preventing macrolide resistance. However, in real-world clinical practice, early microbiological clearance and symptom improvement remain suboptimal, particularly in patients with high disease burden or delayed immune reconstitution. In addition, drug-drug interactions, especially with ART, and tolerability issues may limit treatment effectiveness.
Fluoroquinolones have demonstrated in vitro activity against mycobacteria and possess favorable pharmacokinetic properties, including good tissue penetration. Retrospective studies suggest that the addition of a fluoroquinolone to standard regimens may improve outcomes in disseminated MAC infection, but high-quality prospective evidence is lacking. Therefore, an intensified treatment strategy incorporating a fluoroquinolone during the early phase of therapy may enhance bacterial clearance and improve clinical outcomes.
Study Objectives:
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •HIV infection confirmed
- •Disseminated Mycobacterium avium complex (MAC) infection confirmed by positive culture from a sterile site or positive molecular/sequencing-based detection from a sterile site specimen considered clinically significant
- •Systemic manifestations consistent with disseminated infection
- •Planned initiation of standard antimycobacterial therapy
- •Able and willing to provide written informed consent
排除标准
- •Prior effective antimycobacterial treatment for >14 days before enrollment
- •Known macrolide resistance, if susceptibility data are available
- •Hypersensitivity to macrolides, ethambutol, rifamycins, or fluoroquinolones
- •Baseline QTc >500 ms or history of significant cardiac arrhythmia
- •Uncorrected hypokalemia or hypomagnesemia
- •History of severe adverse reaction to fluoroquinolones, such as tendon rupture or severe neuropathy
- •Severe hepatic impairment or severe renal dysfunction precluding study treatment
- •Concomitant medications that significantly prolong QT interval and cannot be safely discontinued
- •Pregnancy or breastfeeding
- •Coexisting infection requiring non-protocol antimycobacterial therapy, such as active tuberculosis
- •Any condition that, in the investigator's judgment, would interfere with study participation or interpretation of results
研究者
Li Liu
M.D
Shanghai Public Health Clinical Center