Symptoms and General Pathology

Wounds and Injuries

All Conditions

Blood and Lymph Conditions

Rare Diseases

Hyperthermia

Neutropenia

Fever

Febrile Neutropenia

Agranulocytosis

Leukopenia

Cytopenia

Hematologic Diseases

Leukocyte Disorders

Granulocytopenia

The Everion® will be given to the participants for the duration of 2 weeks (fourteen days) with the instruction to wear it all the time, with exception of the time needed for battery charging and the patients' hygiene.

The Everion® device, by Biovotion, Zurich, is a on-skin wearable device measuring health data.

Everion

Eva Brack, MD-PhD

Christa Koenig, MD

In this pilot study the feasibility of continous monitoring of health data with a small, on-skin wearable device (the Everion®, by Biovotion, Zurich) in pediatric patients under chemotherapy for cancer, is studied. Feasibility is assessed by the number of patients wearing the device on seven consecutive days for at least 18h/day, what will be measured by monitored heart rate. Study duration for each participant is 14 days.

No study has proved feasibility of continuous monitoring of health data with a small wearable device such as the device Everion® in pediatric patients. It is not known if children tolerate the device and if data quality sustains with smaller arm circumferences or when worn on the upper leg. Neither is it known if parents and/or patients can and are willing to handle the device in ambulant setting. Therefore, this pilot study assesses the feasibility of continous monitoring of health data with a small, on-skin wearable device (the Everion®, by Biovotion, Zurich) in pediatric patients under chemotherapy for cancer.

Feasibility of Monitoring Health Data in Pediatric Patients Undergoing Chemotherapy

Continuous Monitoring of Health Data With a Wearable Device in Pediatric Patients Undergoing Chemotherapy for Cancer - a Feasibility Pilot Study

The coded study data (from the WD and clinical data) will be uploaded to figshare and made publically available for other researchers.

The primary outcome is defined as at least acceptable (≥50) quality score (worst quality 0, best quality 100) of heart rate during a cumulative duration of ≥18/24h per day (noon to noon), during ≥7 consecutive days within the 14 days of study duration (binary outcome, measured once).

At least acceptable (≥50) quality score (worst quality 0, best quality 100) of oxygen saturation during a cumulative duration of ≥18/24h per day (noon to noon), during ≥7 consecutive days within the 14 days of study duration (binary outcome, measured once).

At least acceptable(≥50) quality score (worst quality 0, best quality 100) of respiration rate during a cumulative duration of ≥18/24h per day (noon to noon), during ≥7 consecutive days within the 14 days of study duration (binary outcome, measured once).

At least acceptable(≥50) quality score (worst quality 0, best quality 100) of core temperature during a cumulative duration of ≥18/24h per day (noon to noon), during ≥7 consecutive days within the 14 days of study duration (binary outcome, measured once).

At least acceptable (≥50) quality score (worst quality 0, best quality 100) of heart rate variability during a cumulative duration of ≥18/24h per day (noon to noon), during ≥7 consecutive days within the 14 days of study duration (binary outcome, measured once).

At least acceptable (≥50) quality score (worst quality 0, best quality 100) of perfusion index during a cumulative duration of ≥18/24h per day (noon to noon), during ≥7 consecutive days within the 14 days of study duration (binary outcome, measured once).

Cumulative length of time with monitored heart rate with at least acceptable quality score (≥50, worst quality 0, best quality 100) per study day (continuous outcomes, measured daily).

Cumulative length of time with monitored oxygen saturation with at least acceptable quality score (≥50 worst quality 0, best quality 100) per study day (continuous outcomes, measured daily).

Cumulative length of time with monitored respiration rate with at least acceptable quality score (≥50, worst quality 0, best quality 100) per study day (continuous outcomes, measured daily).

Cumulative length of time with monitored core temperature with at least acceptable quality score (≥50, worst quality 0, best quality 100)) per study day (continuous outcomes, measured daily).

Cumulative length of time with monitored heart rate variability with at least acceptable quality score (≥50, worst quality 0, best quality 100) per study day (continuous outcomes, measured daily).

Cumulative length of time with monitored perfusion index with at least acceptable quality score (≥50, worst quality 0, best quality 100) per study day (continuous outcomes, measured daily).

Proportion of patients and parents indicating that continuous monitoring with the wearable device (WD) is acceptable per day and per entire study duration and reasons not to wear the device.

Number and description of side effects reported by parents and patients, if applicable. Assessed with questionnaires.

Effort (cumulative number of contacts) for the Investigators.

Effort (cumulative duration of contacts) for the Investigators.

Difference between discrete measurements performed for clinical routine cares of heart rate and the mean of continuously measured heart rate within +/-10min at times of the discrete measurement.

Exploration of potential changes in or specific patterns of all collected signals and their quality scores in combination (heart rate, oxygen saturation, respiration rate, core temperature, skin temperature, heart rate variability, perfusion index, health score (0-100, higher score means better health), galvanic skin response) , within 48 hours before and after clinical diagnosis of fever (ear temperature of ≥39.0°C, or ≥38.5°C if fever is declared for clinical reasons) with or without neutropenia and microbiologically or clinically defined infections, if applicable.

Insel Gruppe AG, University Hospital Bern

The Everion® will be given to the participants for the duration of 2 weeks (fourteen days) with the instruction to wear it all the time, with exception of the time needed for battery charging and the patients' hygiene.

Everion: The Everion® device, by Biovotion, Zurich, is a on-skin wearable device measuring health data.

Everion®

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Switzerland

Region of Enrollment

Acute lymphoblastic leukemia

Other hematologic malignancies

Central nervous system tumor

Solid tumor

Type of malignancy

(i) The WDs were studied for only 14 days and compliance might be different during long-term use.

(ii) The small number of patients precluded an analysis of patient factors (iii) The planned comparison of discrete measurements versus continuously was not feasible because the exact second-wise time point of discrete measurements was not available.

Dr. med. Christa König

Feasibility of Continous Monitoring of Heart Rate With the Wearable Device (WD)

Continous Monitoring of Oxygen Saturation With the WD

Continous Monitoring of Respiration Rate With the WD

Continous Monitoring of Core Temperature With the WD

Continous Monitoring of Heart Rate Variability With the WD

Continous Monitoring of Perfusion Index With the WD

Cumulative Time of Monitoring Heart Rate With the WD

Cumulative Time of Monitoring Oxygen Saturation With the WD

Cumulative Time of Monitoring Respiration Rate With the WD

Cumulative Time of Monitoring Core Temperature With the WD

Cumulative Time of Monitoring Heart Rate Variability With the WD

Cumulative Time of Monitoring Perfusion Index With the WD

Device Acceptance Assessed With Questionnaires

Superficial skin lesion

irritated skin

itching

sweating

Number and Description of Side Effects

Effort for Investigators Assessed by Number of Contacts

Effort for Investigators Assessed by Duration of Contacts

The analysis of differences between discrete measurements and continuously recorded aggregates of vital signs, as defined in the protocol, was found to yield massively distorted results because rapidly changing discretely measured vital signs were compared to aggregated means covering up to 20 min. We deliberately refrain from displaying these nonmeaningful results here.

Comparison

Episodes with fever

Episodes with Infection

The 4 episodes occured in 3 of these 20 patients. The other 17 patients had no episode with fever or infection.

Exploration of Patterns Within the Vital Signs Before Episodes With Fever or Infection

Overall Study

Body Temperature Changes

Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Anti-Bacterial Agents

Amoxicillin

Ciprofloxacin

Antibiotics, Antitubercular

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

ciprofloxacin and amoxicillin

Outpatient management

i.v. antibiotics

inpatient management

Roland A Ammann, MD

Christoph Aebi, MD

Maja Beck-Popovic, MD

Eveline SJM de Bont, MD

Thomas Kuehne, MD

David Nadal, MD

Felix Niggli, MD

Arne Simon, MD

Nicole Bodmer, MD

Hulya Ozsahin, MD

The purpose of this study is to determine whether, in children with cancer presenting with fever in severe chemotherapy-induced neutropenia at low risk for medical complications, oral antibiotics in an outpatient setting after an initial phase of intravenous antibiotics and in-hospital observation for 8 to 22 hours, is not inferior as to safety and efficacy compared to continued intravenous antibiotics given in-hospital.

Details on antimicrobial therapy

* At presentation with FN (fever and neutropenia) and during an initial inpatient observation period of 8 to 22 hours, empirical intravenous broad-spectrum antibiotics are given. Type and dosage are chosen by the treating physician.
* Patients randomized to continued intravenous antibiotics continue with these antibiotics.
* Patients randomized to oral antibiotics receive a combination of oral ciprofloxacin (25 to 30 mg/kg/day, top dose 1500 mg/day) plus oral amoxicillin (65 to 80 mg/kg/day, top dose 2250 mg/day), both given in two doses per day.
* In both groups, the study gives guidelines (for certain situations) and rules (for other situations) when to change and when to stop antibiotics.

Details on clinical and laboratory controls

* During antibiotic therapy, patients are seen daily, either as inpatients or as outpatients according to randomization. Complete blood counts are performed at least every second day.
* After stopping antibiotic therapy and until resolution of severe neutropenia (if applicable), patients are seen every other day, with a complete blood count.
* Patients randomized to outpatient management have the possibility to contact at any time of the day (and night) a pediatric oncologist in case of problems, in order to discuss necessity for emergency control and/or rehospitalization.

Low-risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting

A Prospective Multi-Center Study on Pediatric Patients With Fever in Severe Chemotherapy Induced Neutropenia, Including a Randomized Comparison of Outpatient Management and Oral Antimicrobial Therapy Versus Inpatient Management and Intravenous Antimicrobial Therapy in a Subgroup With Low Risk of Adverse Events (Low-Risk Subgroup Study)

Swiss Cancer League

Bayer

GlaxoSmithKline

Swiss Pediatric Oncology Group

Behaviors and Mental Disorders

Chemotherapy-Induced Febrile Neutropenia

Stress Disorders, Traumatic

Heat Stress Disorders

Cefepime

Cefixime

After randomization, participants assigned to receive outpatient treatment with oral cefixime at a dose of 8 mg/kg/day were discharged. Treatment was provided by the researchers. Subjects were evaluated daily at the outpatient clinic of the hospital. All patients underwent a blood count every 48 to 72 hours. FN event resolution was defined as when the patient remained afebrile and the ANC increased to above 500 per microliter. If fever resumed in the outpatient group, they were re-admitted to the hospital to receive intravenous antibiotics. Resolution of the FN event was defined as the end of participation of the subjects in the study, and they were followed up for an additional 72 hours.

After randomization, participants continued intravenous inpatient antibiotic with cefepime 150 mg/kg/day according to local standard of care guidelines. Subjects were evaluated daily. All patients underwent a blood count every 48 to 72 hours. FN event resolution was defined as when the patient remained afebrile and the ANC increased to above 500 per microliter. If fever resumed, treatment was changed according to clinical guidelines. Resolution of the FN event was defined as the end of participation of the subjects in the study, and they were followed up for an additional 72 hours.

Participants allocated in oral outpatient group were discharged home with oral antibiotic to continue management. Participants were given Cefixime oral suspension (100 mg/5 mL). Antibiotic was given to the caretakers with written instructions about dosage and time of administration. Dosage indicated was 8 mg/kg/day to be given orally as a single dose (max dose 400 mg/day). Oral antibiotic treatment was given until documented ANC \> 500, failure to treatment (restart of fever) or when 14 days of antibiotic were completed (whichever occurred first).

Outpatient oral treatment.

Participants allocated in the intravenous inpatient group continued receiving Cefepime 150 mg/kg/day every 8 hours (max dose 2 grams per dose or 6 grams per day) according to local standard of care guidelines. Intravenous antibiotic treatment was given until documented ANC \> 500, failure to treatment (restart of fever) or when 14 days of antibiotic were completed (whichever occurred first).

Inpatient intravenous treatment.

Martha J. Aviles Robles

Febrile neutropenia (FN) continues to be the infectious complication that most commonly requires hospitalization in pediatric cancer patients undergoing chemotherapy. In recent years, data have been published on the effectiveness of treatment of FN events with oral antibiotics, mainly in developed countries, but data from developing countries continue to be scarce.

Our hypothesis was that early change from initial in-patient intravenous antibiotic treatment to oral outpatient antibiotic treatment in children with cancer and FN is as safe and effective as in-patient intravenous antibiotic management.

The purpose of this clinical study was to determine whether early outpatient oral antibiotic treatment is not inferior in safety and efficacy to in-hospital intravenous antibiotic treatment in pediatric patients with cancer and low-risk FN events.

A multicenter, non-inferiority randomized clinical trial was conducted in three public hospitals in Mexico City. Low-risk FN events were identified in children aged 1 to 18 years. After 48 to 72 hours of receiving intravenous in-hospital antibiotics, children were randomly allocated to receive outpatient oral treatment (cefixime) or to continue in-hospital intravenous treatment (cefepime). Daily monitoring was performed until the resolution of neutropenia. Our outcome of interest was the presence of any unfavorable clinical outcome.

Introduction: Febrile neutropenia (FN) continues to be the infectious complication that most commonly requires hospitalization in pediatric cancer patients undergoing chemotherapy. Classically these patients have been managed as inpatient. In recent years, data have been published on the effectiveness of treatment of FN events with oral antibiotics, mainly in developed countries, but data from developing countries continue to be scarce.

Hypothesis: Our hypothesis was that early change from initial in-patient intravenous antibiotic treatment to oral outpatient antibiotic treatment in children with cancer and FN is as safe and effective as in-patient intravenous antibiotic management.

Objectives: The purpose of this clinical study was to determine whether early outpatient oral antibiotic treatment is not inferior in safety and efficacy to in-hospital intravenous antibiotic treatment in pediatric patients with cancer and low-risk FN events.

Methodology: A multicenter, non-inferiority randomized clinical trial was conducted in three public hospitals in Mexico City. Low-risk FN events were identified in children aged 1 to 18 years.

A complete medical history, physical examination and review of laboratory tests and cultures were performed on all subjects with FN events who were considered low risk. According to local guidelines for the treatment of FN, all subjects began receiving cefepime at a dose of 150 mg/kg/day. Subjects were followed-up daily, and those who met the inclusion/exclusion criteria after 48 to 72 hours of in-hospital intravenous treatment with cefepime were randomly assigned to receive outpatient treatment with oral cefixime at a dose of 8 mg/kg/day or to continue in-hospital intravenous treatment. The treatment was administered by the researchers.

Participants in both treatment groups were evaluated daily by a complete physical examination. Subjects in the outpatient group were evaluated at the outpatient clinic of the hospital. All patients underwent a blood count every 48 to 72 hours. FN event resolution was defined as when the patient remained afebrile and the absolute neutrophil count (ANC) increased to above 500 per microliter. If fever resumed, the antibiotic regimen was modified. If the subjects were in the outpatient group, they were re-admitted to the hospital to receive intravenous antibiotics. Resolution of the FN event was defined as the end of participation of the subjects in the study, and they were followed up for an additional 72 hours.

The occurrence of any of the following conditions was considered an unfavorable clinical outcome: 1) therapeutic failure, defined as the resumption of fever in a patient with persistent neutropenia. For all patients with resumption of fever, the antibiotic regimen was switched, and if the patients were in the outpatient treatment group, they were re-admitted to the hospital; 2) new focus of infection, documented both by the clinical condition and by laboratory and other diagnostic tests; 3) hemodynamic instability, defined as a decrease in blood pressure below the 5th percentile for the patient age that did not revert with the administration of crystalloid solutions; and 4) death.

Sample size: The sample size was calculated to reject a null hypothesis of inferiority, with a non-inferiority margin of presentation of unfavorable clinical outcomes of 15%. A formula including a statistical power of 80% and a one-tailed alpha value of 0.025 was used to calculate the sample size of 2 independent proportions. Based on previous reports of 10% of unfavorable clinical outcomes during the management of FN events, the calculation yielded a total of 63 FN events per group for a total of 126 events.

Randomization: A random sequence balanced by blocks of 4 FN events was generated using a computer program. A physician who did not participate in the subject selection assigned subjects to receive either outpatient oral treatment at home or to continue in-hospital intravenous treatment. If the subjects lived more than 1 hour away from the hospital, they were assigned to a care home to ensure that they could return to the hospital in case of any event. Because the study intervention involved outpatient treatment, the study was open. All patients were provided with the antibiotic free of charge.

Statistical analysis: The focus of analysis was intention-to-treat. For each comparison group, measures of central tendency and dispersion were estimated for continuous variables, and absolute and relative frequencies were determined for discrete and nominal variables. The statistical test performed to test the hypothesis of non-inferiority is very similar to the traditional test for comparison of proportions; the only difference is that the non-inferiority margin is added to the formula, and a p-value \< 0.05 confirms non-inferiority. The statistical program STATA version 14.2 was used for the analysis.

A multicenter, noninferiority randomized clinical trial was conducted in three public hospitals in Mexico City. A complete medical history, physical examination and review of laboratory tests and cultures were performed on all subjects with FN events who were considered low risk. All subjects began receiving intravenous inpatient treatment with cefepime. Subjects were followed-up daily, and those who met the inclusion/exclusion criteria after 48 to 72 hours of in-hospital intravenous treatment were randomly assigned to receive outpatient treatment with oral cefixime or to continue in-hospital intravenous treatment. The treatment was administered by the researchers.

Safety and Efficacy of Ambulatory Versus In-hospital Antibiotic Treatment in Children With Febrile Neutropenia

Safety and Efficacy of Ambulatory Versus In-hospital Antibiotic Treatment in Pediatric Patients With Cancer and Febrile Neutropenia: a Non-inferiority Multicenter Randomized Clinical Trial

Occurrence of therapeutic failure, defined as the resumption of fever in a patient with persistent neutropenia. For all patients with resumption of fever, the antibiotic regimen was switched, and if the patients were in the outpatient treatment group, they were re-admitted to the hospital.

Presence of a new focus of infection, documented both by the clinical condition and by laboratory and other diagnostic tests.

Presence of hemodynamic instability, defined as a decrease in blood pressure below the 5th percentile for the patient age that did not revert with the administration of crystalloid solutions.

Moderate and severe adverse reaction to antibiotics given, described as an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product, which predicts hazard from future administration and warrants prevention or specific treatment, or alteration of the dosage regimen, or withdrawal of the product.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Feasibility of Monitoring Health Data in Pediatric Patients Undergoing Chemotherapy	NCT04134429	Pediatric Cance... Febrile Neutrop... Chemotherapy-in... Oncology	Everion	1 Month - 17 Years	Insel Gruppe AG, University Hospital Bern
Low-risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting	NCT00107081	Fever Neutropenia Cancer	ciprofloxacin a... Outpatient mana... i.v. antibiotic... inpatient manag...	1 Year - 18 Years	Swiss Pediatric Oncology Group
Feasibility of Monitoring Health Data in Pediatric Patients Undergoing Chemotherapy	NCT04134429	Pediatric Cance... Febrile Neutrop... Chemotherapy-in... Oncology	Everion	1 Month - 17 Years	Insel Gruppe AG, University Hospital Bern
Low-risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting	NCT00107081	Fever Neutropenia Cancer	ciprofloxacin a... Outpatient mana... i.v. antibiotic... inpatient manag...	1 Year - 18 Years	Swiss Pediatric Oncology Group
Safety and Efficacy of Ambulatory Versus In-hospital Antibiotic Treatment in Children With Febrile Neutropenia	NCT04000711	Chemotherapy-In...	Outpatient oral... Inpatient intra...	1 Year - 18 Years	Hospital Infantil de Mexico Federico Gomez

Spots Global Cancer Trial Database for fever and neutropenia