Nurse-Led Sepsis Scoring System for Adult Febrile Neutropenia: Protocol for a Two-Phase Clinical Prediction Model Study With Remote Patient Monitoring

Background: Adults with hematological malignancies who develop febrile neutropenia (FN) face elevated risks of sepsis, intensive care admission, and treatment interruptions. Early sepsis detection is challenging, as classical clinical signs are often attenuated or delayed in this population. Current risk stratification tools demonstrate limitations when applied to adults with FN. A tailored, nurse-led scoring system integrating clinical, laboratory, and physiological predictors may enhance early sepsis identification. Objective: This 2-phase study aims to develop and internally validate a nurse-led sepsis risk score for adults with FN in phase I and to temporally validate its performance in phase II. The new score will be compared to the MASCC risk index, CISNE, NEWS2_ and qSOFA at FN onset . The secondary objectives include evaluating associations between risk groups and remote patient monitoring alerts within 24 hours of FN onset, interrater agreement, and bedside feasibility. Methods: The study is being conducted in the hematology and bone marrow transplantation department of a tertiary care hospital in Bengaluru, India. Phase I uses a nested matched case-control design within a retrospective cohort of approximately 140 patients with FN. We will analyze clinical, laboratory, and physiological predictors measured at FN onset using multivariable conditional logistic regression, with internal validation via bootstrapping. In Phase II, which utilizes a prospective temporal validation cohort, bedside nurses will calculate the proposed score at FN onset alongside the MASCC, CISNE, NEWS2, and qSOFA scores A substudy will include additional nurses scoring independently to assess interrater agreement and feasibility. Two blinded reviewers will adjudicate phase I outcomes within 14 days of FN onset, while assessors blinded to all scores will adjudicate phase II outcomes within the same time frame. The primary outcome is sepsis within 14 days of FN onset. Phase II evaluates discrimination, calibration, and comparative diagnostic performance. Results: We obtained ethics approval in April 2025, and the study was registered in June 2025 (CTRI/2025/06/088290). The initial phase I derivation was completed in November 2025, using sepsis within 14 days of FN onset as the primary outcome. A protocol amendment in September 2026 harmonized the outcome window to 14 days, prompting rederivation of the model and superseding the initial analysis. Phase II commenced in December 2025. As of September 2026, enrollment and data collection were ongoing, with study completion anticipated in December 2026. Main results are expected in 2027. Conclusions: This protocol evaluates an FN-specific, nurse-led sepsis score integrating clinical and laboratory predictors with contactless physiological measurements. We will examine remote patient monitoring alerts as secondary markers of clinical instability. Validation findings will establish the score's predictive performance and inform future implementation studies.