Plasma Host-Microbe Proteomics to Predict Complications in High-risk Febrile Neutropenia

NCT07277387 | Not Yet Recruiting

• 1 other identifier: COMBITYPES-FN
• Study Type: observational
• Target: 350
• Locations: 1 country
• Sites: 3

Brief 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. 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.

Conditions

Febrile Neutropenia

Keywords

febrile neutropenia; hematologic malignancy; proteomics; sepsis; biomarkers; septic shock; mass spectrometry

Outcome Measures

Primary Outcomes (1)

• 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.

  Within 7 days from fever onset.

Secondary Outcomes (5)

• 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).

Study Arms (1)

High-risk FN cohort

Adult onco-hematologic inpatients meeting inclusion criteria; two plasma draws at fever onset and 48 h.

Biological: Plasma and DNA sample collection for proteomic and genomic analysis

Interventions

Plasma and DNA sample collection for proteomic and genomic analysis BIOLOGICAL

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.

High-risk FN cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Oncohematologic Patients With Febrile Neutropenia

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Instituto de Investigación Biomédica de Salamanca: lead

Study Sites (3)

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona, Spain

Location

Complejo Asistencial Universitario de Salamanca

Salamanca, Salamanca, 37007, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Sevilla, Spain

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood (10 mL) will be collected in EDTA tubes at two time points: (1) at fever onset before the initiation of empirical antibiotic therapy and (2) 48 hours later. Plasma will be separated by centrifugation, aliquoted, and stored at -80°C until proteomic analysis. In addition to plasma, residual buffy coat fractions will be retained for DNA extraction to enable future genomic or metagenomic studies related to host or microbial signatures. All biospecimens will be pseudonymized and stored at the BioSepsis Laboratory (IBSAL) and subsequently transferred to the CAUSA Biobank for long-term storage and controlled access. Samples will be registered in the Spanish National Biobank Registry, and their use in future studies will require approval by the relevant Research Ethics Committee.

MeSH Terms

Conditions

Febrile Neutropenia; Hematologic Neoplasms; Sepsis; Shock, Septic

Condition Hierarchy (Ancestors)

Neutropenia; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Neoplasms by Site; Neoplasms; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Jesús Francisco Bermejo Martín, MD PhD

  Centro Asistencial Universitario de Salamanca (CAUSA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jesús Francisco Bermejo Martín, MD PhD

CONTACT

+34923 29 45 41; jfbermejo@usal.es

Nadia García Mateo, PhD

CONTACT

+34923 29 45 41; nadiagarciamateo@ibsal.es

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 30 Days
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: December 11, 2025
• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Data will be available starting 12 months after publication of the primary results and will remain accessible for at least 5 years thereafter.
• Access Criteria: Qualified researchers with a methodologically sound proposal may request access. Requests will be reviewed by the study's Data Committee/Steering Committee. Applications should be addressed to the Principal Investigator (Jesús Francisco Bermejo Martín). A Data Use Agreement (DUA) will be required, including commitments to non-reidentification, appropriate data security, and mandatory citation of both the source and dataset DOI. Applicants may also be required to share their analytical code and a publication plan prior to authorization.

Locations

ES (3)