Swiss 2024 Continous Fever Monitoring in Pediatric Oncology Patients

Swiss 2024 Fever Monitoring Study: An Double-blinded, Randomized Controlled Multiple Crossover Superiority Trial on Continuous Fever Monitoring in Paediatric Patients With Cancer at Risk for Fever in Neutropenia

In children and adolescents undergoing chemotherapy for cancer, fever in neutropenia (FN) is the most frequent potentially lethal complication of chemotherapy for cancer. Emergency hospitalization and empirical treatment with i.v. broad-spectrum antibiotics have reduced lethality from >50% in certain high risk situations to <1%. Fever without neutropenia is a further complication requiring emergency evaluation and often emergency treatment.

Continuous monitoring of fever leads to earlier fever detection compared to the usual discrete fever measurements performed only for clinical reasons. Earlier detection of fever leads to earlier assessment and treatment and thus can reduce the risk of complications.

This study primarily aims to assess, in pediatric patients undergoing chemotherapy for cancer, the efficacy of automated fever alerts resulting from continuous fever monitoring (CFM) using a wearable device (WD), measured by the duration of intravenous antibiotics (i.v. AB) given for any cause.

Study Overview

• Status: Not yet recruiting
• Conditions: Pediatric Oncology Patients With Risk for Infections
• Intervention / Treatment: Other: Automated fever alerts

Detailed Description

Primary objective

The primary objective of this study is to determine if CFM fever alerts (CFM-FA) automatically sent by a WD reduce the duration of i.v. antibiotics application in children and adolescents treated with myelosuppressive chemotherapy for cancer.

Secondary objectives

Regarding safety

A. Number of fever episodes (FE) with safety relevant events (SREs)

B. Number of false alerts

C. Number of missed alarms

Regarding efficacy

D. Delay of chemotherapy application

E. Duration of antimicrobial application except i.v. antibiotics

F. Number of FEs diagnosed below or at temperature limit (TL) versus above TL

G. FEs according to chemotherapy intensity

H. WD measured core temperature at time of fever detection by ear thermometer

I. FEs reported outside TARs

J. Quality of life Questionnaire

K. Assessment of the side-effects of the WD

Tertiary objective

L. Comparison of continuously recorded core temperature of the WD with results of discrete measurements of tympanic temperature

M. Pattern search using data mining

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eva K Brack, MD, PhD; Phone Number: +41316641943; Email: eva.brack@insel.ch
• Study Contact Backup: Name: Roland Ammann, MD, Prof.; Email: info@statconsultammann.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 2010
    • Childrens' Clinc Bern, Inselspital Bern
    • Contact: Eva K Brack, MD, MD-PhD; Email: eva.brack@insel.ch
    • Contact: Roland Ammann, MD, Prof; Email: info@statconsultammann.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Chemotherapy treatment because of any malignancy expected to last ≥2 months at time of recruitment for myelosuppressive therapy, or at least 1 cycle of myeloablative chemotherapy followed by hematopoietic stem cell transplantation
• Age ≥1 month and <18 years at time of recruitment
• Written informed consent from patients and/or parents

Exclusion Criteria:

• Neonates <1 months
• Local skin disease prohibiting wearing of the WD
• Denied written informed consent from patients and/or parents
• Inclusion of vulnerable participants mandatory as vital signs and FN episodes differ significantly in children and adults

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention "With CFM alerts" arm; Routine clinical care, which includes, among others, discrete fever measurements using ear thermometers in case of clinical deterioration or suspected fever, at the discretion of patients where applicable, parents and the treating team; Plus CFM with a CORE® WD running, with alerts being sent automatically to participants if the CFM detects an estimated core body temperature fulfilling the fever criterion of the respective study site (≥38.5°C or 39.0°C).	Other: Automated fever alerts; Fever alerts are automated sent to participants if fever is detected
No Intervention: Control "Without CFM alerts" arm; Routine clinical care as in "With CFM alerts"; Plus CFM with a CORE® WD running as in "With CFM alerts", but with alerts being sent only if a clinically dangerous temperature of ≥40.0°C is detected, which will very rarely be the case before fever is detected by routine clinical care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary objective of this study is to determine if CFM fever alerts (CFM-FA) automatically sent by a WD reduce the duration of i.v. antibiotics application in children and adolescents treated with myelosuppressive chemotherapy for cancer.	The cumulative duration of i.v. antibiotics applied	3 to 9 month per patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of fever episodes (FE) with safety relevant events (SREs)	Number of FE with SREs	3 to 9 month per patient
Number of false alerts	Number of false alerts	3 to 9 month per patient
Number of missed alarms	Number of missed alarms	3 to 9 month per patient
Delay of chemotherapy application	Duration of delay of chemotherapy application in days	3 to 9 month per patient
Duration of antimicrobial application except i.v. antibiotics	Duration of antimicrobial application except i.v. antibiotics	3 to 9 month per patient
Number of fever episodes (FE) diagnosed below or at temperature limit (TL) versus above TL	Number of FEs diagnosed below or at TL versus above TL	3 to 9 month per patient
FEs according to chemotherapy intensity	Amount of fever episodes according to chemotherapy intensity	3 to 9 month per patient
Wearable Device (WD) measured core temperature at time of fever detection by ear thermometer	WD measured core temperature at time of fever detection by ear thermometer	3 to 9 month per patient
FEs reported outside times of risk (TARs)	Amount of fever episodes reported outside TARs	3 to 9 month per patient
Quality of life Questionnaire	Proportion of participants indicating that wearing a WDs is acceptable/unacceptable, not increasing anxiety/increasing anxiety, providing/not providing security, increase burden/effort or not	Month 1, 6 and at study completion, an average of 1 year
Assessment of the side-effects of the WD	Side effects reported by participants, if applicable	Through study completion, an average of 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of continuously recorded core temperature of the WD with results of discrete measurements of tympanic temperature	Difference between discrete measurements of core temperature	Through study completion, an average of 1 year
Vital sign pattern search in monitored core temperature using data mining	Exploration of potential changes in or specific patterns of all measured temperature signals within 48 hours before clinical diagnosis of fever	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Collaborators: ETH Zurich
• Investigators: Principal Investigator: Eva K Brack, MD, PhD, Childrens' Clinic Bern, Inselspital, Bern

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: June 8, 2023
• First Submitted That Met QC Criteria: July 3, 2023
• First Posted (Actual): July 11, 2023

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: July 3, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Fever; Neutropenia; Pediatric oncology; Wearable device; Continous monitoring; Core temperature; Automated alerts
• Additional Relevant MeSH Terms: Body Temperature Changes; Neoplasms; Fever
• Other Study ID Numbers: Swiss 2024 Fever Monitoring

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Publication in international journal of study protocol and results
• IPD Sharing Time Frame: End of study
• IPD Sharing Access Criteria: All study information will be made publically available as long as the patient as signed the informed consent for data sharing
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No