A Multicenter Prospective Observational Study on the Plasma Proteomic Profiling of Human and Microbial Proteins for the Early Identification of Biomarker Combinations (Combitypes) Associated With Complications in Oncohematologic Patients With Febrile Neutropenia
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 350
- 试验地点
- 3
- 主要终点
- Identification of plasma host-microbial proteomic signatures (combitypes) associated with major complications in febrile neutropenia.
研究概览
简要总结
Febrile neutropenia (FN) is a common oncologic emergency in patients with hematologic malignancies, associated with high morbidity and mortality. Early identification of patients at higher risk of complications such as sepsis or septic shock is critical to optimize antimicrobial management.
This study aims to characterize the human and microbial plasma proteome using high-resolution mass spectrometry to identify biomarker combinations ("combitypes") capable of predicting complications in oncohematologic patients with FN.
A cohort of 350 adult patients with high-risk FN and initially uncomplicated clinical presentation will be enrolled across three tertiary hospitals. Plasma samples will be collected at fever onset (before antibiotic initiation) and after 48 hours. Proteomic data will be integrated with clinical information using multivariate and machine learning models to develop a predictive model for complications.
详细描述
This multicenter, prospective, observational study will evaluate whether combined proteomic profiles of host and microbial origin can predict complications in patients with hematologic malignancies presenting with high-risk febrile neutropenia (FN).
FN is defined as an oral temperature ≥38.3 °C once or ≥38.0 °C for ≥1 hour in patients with an absolute neutrophil count (ANC) <500 cells/mm³ or expected to decrease below that threshold within 48 hours. Despite empirical broad-spectrum antibiotics, up to 50% of these patients develop sepsis, and 10% progress to septic shock.
Current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) have limited specificity in this immunocompromised population. This study proposes a novel integrative proteomic approach based on mass spectrometry to simultaneously quantify host and microbial proteins in plasma, identifying molecular patterns associated with poor outcomes.
Plasma samples (10 mL, EDTA) will be obtained at two time points: the first febrile episode (prior to antibiotic administration) and 48 hours later. Proteins will be processed using PreOmics® ENRICHplus technology and analyzed via LC-MS/MS on an Evosep One-timsTOF Pro2 platform. Differentially expressed proteins will be identified using a data-independent acquisition (DIA-PASEF) workflow and validated in a subset of 200 patients through targeted mass spectrometry.
Clinical, analytical, and microbiological data will be collected via the REDCap platform. Machine learning models (XGBoost, SHAP interpretability) will be used to generate a predictive risk model for complications, integrating proteomic and clinical data.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Adults (≥18 years).
- •Written informed consent provided by patient or legal representative.
- •Diagnosis of hematologic malignancy under induction chemotherapy, post-allogeneic hematopoietic stem cell transplantation, or CAR-T therapy.
- •High-risk febrile neutropenia (ANC ≤ 100 cells/mm³, expected duration ≥ 7 days, or significant comorbidities).
- •Fever defined as oral temperature ≥38.3 °C once or ≥38.0 °C for ≥1 hour.
- •Hospitalized or requiring immediate admission at the time of FN diagnosis.
- •´- Initial uncomplicated clinical presentation, with no previous infection or colonization by multidrug-resistant bacteria.
- •Eligible for initial monotherapy with broad-spectrum empirical antibiotic.
- •Availability for serial plasma sampling and clinical follow-up.
排除标准
- •Age <18 years.
- •Low-risk FN according to MASCC/CISNE criteria.
- •Initial sample collected after antibiotic administration.
- •Decline or inability to provide informed consent.
- •Any condition preventing safe participation or reliable sample collection.
- •Fever induced by noninfectious causes (considered as adjustment factor, not exclusion).
研究组 & 干预措施
High-risk FN cohort
Adult onco-hematologic inpatients meeting inclusion criteria; two plasma draws at fever onset and 48 h.
干预措施: Plasma and DNA sample collection for proteomic and genomic analysis (Biological)
结局指标
主要结局
Identification of plasma host-microbial proteomic signatures (combitypes) associated with major complications in febrile neutropenia.
时间窗: Within 7 days from fever onset.
Evaluation of proteomic profiles (human and microbial) associated with hemodynamic instability, sepsis, septic shock, or death.
次要结局
- Dynamic changes in plasma proteome over 48 hours(0-48 hours)
- Predictive performance of identified combitypes versus conventional biomarkers (CRP, PCT)(Up to 7 days.)
- Correlation between microbial proteomic profiles and microbiologically documented infections(During hospitalization (up to 30 days).)
- Development of a predictive model for complications(Study duration (36 months).)
- Validation of selected protein biomarkers by targeted mass spectrometry(By end of study (month 36).)