Adjunctive Fosfomycin for Treatment of Staphylococcus Aureus Bacteraemia: Protocol for a Pooled Post-hoc Analysis of Two Randomised Clinical Trials
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 369
- 试验地点
- 6
- 主要终点
- Treatment success at 8 weeks from the time of randomisation
研究概览
简要总结
Staphylococcus aureus bacteraemia is a frequent and life-threatening infection, despite current standard antibiotic monotherapy. This study aims to clarify the role of fosfomycin as an adjunctive therapy for improving outcomes in patients with this serious infection. Two clinical trials suggested that adjunctive fosfomycin therapy might offer a clinical benefit in certain cases, but the results are inconclusive. We aim to analyse pooled data from these trials in order to identify subgroups of patients that might benefit most from this therapy.
详细描述
Background. Improving outcomes in patients with methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus bacteraemia (SAB) is a critical healthcare goal. Two recent randomised clinical trials (RCTs), the BACSARM trial and the SAFO trial, assessed the efficacy of fosfomycin as an adjunctive therapy for MRSA and MSSA SAB respectively. Although neither trial demonstrated statistically significant differences in their primary endpoints of treatment success and reduced mortality respectively, both studies observed lower rates of persistent bacteraemia in the fosfomycin groups.
Methods. We will perform a post-hoc analysis of pooled individual patient data from the BACSARM and SAFO trials, which will be referred to as the BACSAFO study. The primary exposure of interest is fosfomycin adjunctive therapy, and the primary outcome will be treatment success at 8 weeks, defined as the patient being alive, without signs of relapse, and showing improvement in clinical signs and symptoms. We will use both Bayesian and frequentist methodologies: the Bayesian analysis will use a hierarchical Bayesian log-binomial model, while the frequentist analysis will apply a hierarchical log-binomial model. In addition, we will investigate whether adjunctive fosfomycin is particularly beneficial in specific patient subgroups (created according to age, methicillin resistance, place of acquisition, and complicated bacteraemia status).
Discussion. The BACSAFO study aims to clarify the role of fosfomycin as an adjunctive therapy for improving outcomes in SAB patients. Although previous trials have not demonstrated significant differences in the primary endpoints, the significant reductions in rates of persistent bacteraemia observed suggest that fosfomycin might offer a clinical benefit in certain cases. By analysing pooled data and attempting to identify subgroups that might benefit most, this study has the potential to refine treatment strategies and inform trial design and planning for future RCTs investigating combination antibiotic therapies for SAB.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Retrospective
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
- •All patients included in the BACSARM and SAFO clinical trials.
排除标准
- •For both trials: polymicrobial bacteraemia, severe clinical status with expected survival < 24 hours, severe liver disease with Child-Pugh score class C, diagnosis of prosthetic infective endocarditis, allergy or known resistance to study drugs, pregnancy at the time of inclusion, inclusion in another clinical trial.
- •For the BACSARM trial: diagnosis of MRSA pneumonia, prior history of eosinophilic pneumonia, use of additional antibiotic therapy with microbiological activity against MRSA.
- •For the SAFO trial: prior history of myasthenia gravis, acute SARS-CoV2 infection.
结局指标
主要结局
Treatment success at 8 weeks from the time of randomisation
时间窗: 8 weeks from the time of randomisation
A composite outcome available from the information collected in both trials and based on the fulfilment of all the following criteria: * Alive at week 8 from the time of randomisation. * Absence of relapse within 8 weeks after randomisation, defined as isolation of S. aureus in blood cultures after the index blood cultures were cleared. * Improvement of clinical signs and symptoms as assessed by investigators of the BACSARM and SAFO trials at week 8 from the time of randomisation.
次要结局
- Persistent bacteraemia(At days 3 and 7 from the time of randomisation)
- Mortality at days 14, 30 and 60 from the time of randomisation(Days 14, 30 and 60 from the time of randomisation)
- Adverse events leading to treatment discontinuation(During the time that adjunctive fosfomycin therapy was administered)
研究者
Francesc Escrihuela-Vidal
Medical Doctor
Hospital Universitari de Bellvitge