Novel Biomarkers for Invasive Aspergillosis
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 226
- 试验地点
- 2
- 主要终点
- Diagnostic accuracy of serum bmGT
研究概览
简要总结
Diagnosis of invasive aspergillosis remains difficult, and is often based on a combination of patient characteristics, radiological and microbiological findings. To data, galactomannan (GM) is the only well-validated biomarker available. However, GM still has its shortcomings. There is therefore a need for new, complementary biomarkers. In this study, two of those tests, bis(methylthio)gliotoxin (bmGT) and a lateral flow device, will be validated in a hematological population, and compare it to GM.
详细描述
Diagnosis of invasive aspergillosis is often difficult to achieve with certainty, as this requires direct evidence of invasive growth on histopathological examination. A probable diagnosis can be suspected based on both clinical and mycological evidence of the disease, in presence of a susceptible patient. The EORTC-MSG guidelines offer a widely accepted basis for this diagnosis. Under these guidelines, mycological evidence can consist of a positive culture of aspergillus spp, or of detection of galactomannan (GM) in a relevant body sample. GM is a part of the Aspergillus mould and can be detected using a commercially available immunoenzymatic sandwich microplate assay. However, like most biomarkers, galactomannan is far from a perfect biomarker. Several beta-lactam antibiotics are known to cause false positives, and anti-mould therapy has been reported to significantly lower the sensitivity[1]. Additional biomarkers that could circumvent these problems would therefore be beneficial.
A potential new target is gliotoxin (GT), a secondary metabolite of several fungi, the most clinically important of which is Aspergillus[2]. GT is released during invasive growth, and can therefore be used as a biomarker of invasive fungal disease by GT-producing fungi. However, GT is quickly removed by red blood cells from circulation, making it an unreliable marker[3]. A degradation product of GT, bis(methylthio)gliotoxin (bmGT), appears to be more stable as it is not taken up by red blood cells. Serum bmGT or bmGT in bronchoalveolar lavage (BAL) fluid has already been shown in small studies to be a potential marker of invasive aspergillosis, especially when used in combination with GM[3-5].
Recently, another highly specific test has become available, based on detection of an extracellular glycoprotein secreted during the growth of Aspergillus species, using a monoclonal antibody (JF5) in an immunochromatographic lateral-flow device (LFD)[6,7]. This test allows fast (<15 minutes) testing using a commercially available device.
In this study, both the LFD and bmGT will be characterized and validated in a hematological population, and compared to GM.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 16y at start of study
- •One of the following diagnoses:
- •De novo, refractory or relapsed AML/MDS receiving intensive chemotherapy
- •De novo, refractory or relapsed ALL/T-lymphoblastic lymphoma receiving intensive chemotherapy
- •Aplastic anemia requiring ATG therapy
- •Any patient admitted for either autologous or allogeneic hematopoietic stem cell transplantation
- •Written informed consent obtained from the patient
排除标准
- •AML or ALL beyond the specified inclusion criteria
- •Directed treatment for possible, probable, or proven invasive aspergillosis, at moment of screening, or with end of treatment < 6 weeks at screening, or no complete response according to EORTC/MSG criteria, or complete response achieved < 6 weeks at time of screening.
结局指标
主要结局
Diagnostic accuracy of serum bmGT
时间窗: 2 weeks
Determine the diagnostic accuracy (specificity, sensitivity predictive values, accuracy and other key diagnostic values) of serum bmGT in the diagnosis of invasive aspergillosis, using the revised EORTC criteria as gold standard.
次要结局
- Diagnostic accuracy of a combination of serum bmGT and serum GM(2 weeks)
- Prognostic value of serum bmGT(6 weeks)
- Renal and hepatic influence on bmGT(2 weeks)
- Compare bmGT-HPTLC to bmGT-LC/MS(Same day)
- Diagnostic accuracy of LFD(2 weeks)
- Prognostic value of serum bmGT kinetics(6 weeks)
- Diagnostic accuracy of BAL bmGT(2 weeks)