Febrile NeutropeniaNCT07277387
Plasma Host-Microbe Proteomics to Predict Complications in High-risk Febrile Neutropenia
An observational study of Febrile Neutropenia, run by Instituto de Investigación Biomédica de Salamanca at 3 sites in Spain.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Febrile Neutropenia
- What is being tested?
- Plasma and DNA sample collection for proteomic and genomic analysis
- How many people
- 350 participants
- Where
- 3 sitesSpain
- Study dates
- 9 Jun 2026to Jan 2029
- How long will I take part?
- 30 Days
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Oncohematologic Patients With Febrile Neutropenia
Who may be able to join
- 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.
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- ´- 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.
Who cannot join
- 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).
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Spain3 sites, 3 recruiting
- Not yet recruiting
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona
- Recruiting
Complejo Asistencial Universitario de Salamanca
Salamanca, Salamanca, 37007
Jesús Francisco Bermejo Martín, PhD, +34923 29 45 41, jfbermejo@usal.es
- Not yet recruiting
Hospital Universitario Virgen Macarena
Seville, Sevilla
About this study
Official title: 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
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.
Read the detailed description
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.
This study is expected to establish a new decision-support tool for early identification of high-risk FN patients, facilitating personalized antimicrobial strategies and improved prognosis.
- Conditions
- Febrile Neutropenia
- Being tested
- Plasma and DNA sample collection for proteomic and genomic analysis
- Keywords
- febrile neutropenia, hematologic malignancy, proteomics, sepsis, biomarkers, septic shock, mass spectrometry
- Medical subject headings
- Febrile Neutropenia, Hematologic Neoplasms, Sepsis, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasma and DNA sample collection for proteomic and genomic analysisBiological
Collection of 10 mL of peripheral blood in EDTA tubes at fever onset (before antibiotic initiation) and 48 hours later for proteomic and genomic analysis. Samples are processed to obtain plasma and DNA, which will be used for mass spectrometry-based proteomics and potential metagenomic studies.
| Study group | Role | What they receive |
|---|---|---|
| High-risk FN cohort | Adult onco-hematologic inpatients meeting inclusion criteria; two plasma draws at fever onset and 48 h. Receives: Biological: Plasma and DNA sample collection for proteomic and genomic analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of plasma host-microbial proteomic signatures (combitypes) associated with major complications in febrile neutropenia.
Evaluation of proteomic profiles (human and microbial) associated with hemodynamic instability, sepsis, septic shock, or death.
Measured: Within 7 days from fever onset.
Secondary outcomes (5)
Dynamic changes in plasma proteome over 48 hours
Assessment of longitudinal variations in host and microbial protein levels between baseline and 48 hours.
Measured: 0-48 hours
Predictive performance of identified combitypes versus conventional biomarkers (CRP, PCT)
Comparison of ROC-AUC for new proteomic models against current inflammatory markers.
Measured: Up to 7 days.
Correlation between microbial proteomic profiles and microbiologically documented infections
Association between detected microbial peptides and confirmed pathogens.
Measured: During hospitalization (up to 30 days).
Development of a predictive model for complications
A predictive risk model for complications will be developed using machine-learning algorithms (XGBoost) based on the integration of plasma proteomic data and relevant clinical parameters collected at fever onset and during follow-up. The model will be trained and internally validated within the full study cohort using cross-validation techniques to optimize predictive performance and minimize overfitting.
Measured: Study duration (36 months).
Validation of selected protein biomarkers by targeted mass spectrometry
Selected protein biomarkers previously identified through discovery-phase proteomic profiling will be validated using targeted LC-MS/MS mass spectrometry in plasma samples from 200 patients within the study cohort. This validation phase will assess the analytical performance (including reproducibility, accuracy, and sensitivity) of the selected biomarkers, as well as their clinical relevance in predicting complications such as hemodynamic instability, sepsis, septic shock, or death. This outcome cannot be divided into sepparate ones, as biomarker expression will be analyzed as a whole, given the fact that until the trial begins, the biomarkers associated with complications in oncohematologic patients with febrile neutropenia will be unkown. This outcome will determine the feasibility of implementing the identified biomarkers as prognostic tools in routine clinical practice for the early risk stratification of patients
Measured: By end of study (month 36).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2025
- Study start9 Jun 2026
- Primary completionDec 2028 (estimated)
- Study completionJan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Febrile NeutropeniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 350 participants (estimated)
- Target duration
- 30 Days
Sponsor and investigators
- Lead sponsor
- Instituto de Investigación Biomédica de Salamanca
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jesús Francisco Bermejo Martín, MD PhD, Principal investigator, Centro Asistencial Universitario de Salamanca (CAUSA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07277387
- Sponsor's protocol ID
- COMBITYPES-FN
- Status last verified
- Apr 2026
- First submitted
- 18 Nov 2025
- Last updated
- 15 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Following anonymization, individual participant-level data supporting the publications will be made available. These data include demographic and clinical variables collected in REDCap. A data dictionary, eCRF, and-when possible-analysis scripts (R/Python) and FAIR-compliant metadata will also be provided. Data will be hosted within the controlled infrastructure of the project (XNAT/Core-lab) and, for controlled dissemination, within the Zenodo community of IBSAL, with DOI assignment and regulated access, in accordance with the GDPR/LOPDGDD and the study protocol as approved by the Research Ethics Committee.