Heart RateHRVNCT04103151
Heart Rate Variability in Febrile Young Infants
An observational study of Heart Rate and Variability, run by KK Women's and Children's Hospital at 1 site in Singapore.
Trial summary
Febrile infants younger than 3 months old present a diagnostic dilemma to the emergency physician. Tension remains between the need for early aggressive intervention among patients with suspected sepsis and the global phenomena of increasing antibiotic resistance. Read more about this study
- Who is it for?
- Ages 1 day to 3 months
- Conditions the study is for
- Heart Rate, Variability, Triage
- What is being tested?
- Single lead ECG
- Type of treatment
- Medical device
- How many people
- 330 participants
- Where
- 1 siteSingapore
- Study dates
- 11 Dec 2017to 31 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
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 1 day to 3 months
- All sexes
- No healthy volunteers
- Child
Study population: 330 infants < 3 months presenting with fever. Fever is defined as an axillary or rectal temperature ≥ 38oC. 75 infants < 3 months (clinically well) presenting without fever. These include young infants presenting for neonatal jaundice or other non-febrile conditions.
Who may be able to join
- Infants < 3 months presenting to the ED will be included (both febrile and non-febrile) Febrile infants are those with an axillary or rectal temperature ≥ 38oC at triage and/or outside of the hospital. OR Non-febrile infants include those presenting to the ED for serum bilirubin checks or otherwise
Who cannot join
- Infants who are in active resuscitation for septic shock. Infants of parents who refused to give informed consent. Premature infants delivered at a gestation of < 35 weeks.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Rapid Triage for Serious Infections in Infants Younger Than 3 Months Using A Novel Heart Rate Variability Tool
Febrile infants younger than 3 months old present a diagnostic dilemma to the emergency physician. Tension remains between the need for early aggressive intervention among patients with suspected sepsis and the global phenomena of increasing antibiotic resistance.
The investigators aim to: (1) To study the association between heart rate variability (HRV) and the presence of a serious infection (SI) among infants younger than 3 months old. The investigators hypothesize that a reduced HRV is associated with the presence of SI. (2) To compare HRV between febrile infants < 3 months with non-febrile infants. The investigators hypothesize that the variability will be reduced in febrile infants with SIs when compared to non-febrile well infants, but not among febrile infants without SIs when compared to non-febrile well infants. (3) To study if HRV will provide incremental diagnostic information over current triage tools.
Read the detailed description
Febrile young infants younger than 3 months old present a diagnostic dilemma to the pediatric emergency department (ED) physician. The potential for a missed serious infection (SI) poses the threat of premature death and long-term disability among these infants. Despite decreasing early-onset neonatal sepsis rates due to obstetric prevention strategies, high rates of hospitalization and administration of parenteral antibiotics occur in this age group. Continual tension remains between the need for early and aggressive intervention among patients suspected with sepsis and the global phenomena of increasing antibiotic resistance. Research networks have attempted to build diagnostic algorithms to guide the identification of these ill infants. These are often useful as adjuncts to the clinician's gestalt, but generalizability remains questionable.
Vital signs are of paramount importance in recognizing ill children and have been used in pediatric early warning system scores (PEWS) and various triage systems. Vital signs have resurfaced as the focus of research in recent years, with various groups purposing to update evidence-based normal heart rate ranges among children. Normative heart rate ranges are infamously difficult to define due to the hemodynamic lability in these young infants, multiple confounders for abnormal heart rate, and the variable physiological response during acute stress states.
Previous pilot data showed that the Advanced Paediatric Life Support (APLS) and Fleming (<10th or >90th centile) guidelines performed with the highest sensitivity (66.0% and 62.6%, respectively) and the highest Negative Predictive Value (NPV) (73.3% and 71.4%, respectively). No single guideline reached a sensitivity of greater than 70%.
Objectives and Hypothesis
- To study the association between heart rate variability (HRV) and the presence of a serious infection (SI) among infants younger than 3 months old. The investigators hypothesize that a reduced HRV is associated with the presence of SI.
- To compare HRV between febrile infants < 3 months with non-febrile infants. The investigators hypothesize that the variability will be reduced in febrile infants with SIs when compared to non-febrile well infants, but not among febrile infants without SIs when compared to non-febrile well infants.
- To study if HRV will provide incremental diagnostic information over current triage tools.
- Conditions
- Heart Rate, Variability, Triage, Decision Support Techniques
- Being tested
- Single lead ECG
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single lead ECGDevice
Heart Rate Variability will be monitored using a single lead electrocardiogram
| Study group | Role | What they receive |
|---|---|---|
| Febrile infants | Febrile Infants less than 3 months presenting to the emergency department with a temperature of ≥ 38oC. Receives: Device: Single lead ECG | |
| Afebrile infants | Afebrile Infants less than 3 months presenting to the emergency department Receives: Device: Single lead ECG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with Serious Infections
Serious infections are defined by: Sepsis, meningitis, lobar pneumonia, osteomyelitis, abscess, and urinary tract infection
Measured: Within 2 weeks of hospitalisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2019
- Study start11 Dec 2017
- Primary completion31 Dec 2021
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart RateStudies of the same condition, open and under way.
- More trials run by KK Women's and Children's HospitalThe sponsor's other registered studies.
- 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
- 330 participants (actual)
Sponsor and investigators
- Lead sponsor
- KK Women's and Children's Hospital
- Sponsor type
- Other government
- Collaborators
- National Medical Research Council (NMRC), Singapore
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04103151
- Sponsor's protocol ID
- HRV-INFANTS-2017
- Acronym
- HRV
- Status last verified
- Mar 2024
- First submitted
- 8 Sep 2019
- Last updated
- 6 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will be shared with current study team. Sharing of de-identified data with collaborators will be reviewed by the study team.
Publications
Choa ZX, Raveentheran G, Khoo ZX, Ong GY, Wong L, Piragasam R, Ganapathy S, Chong SL. Prevalence of serious bacterial infections and performance of inflammatory markers in febrile infants with and without proven viral illness. Emerg Med J. 2025 Oct 20;42(11):721-727. doi: 10.1136/emermed-2024-214435.
PubMed 40335269Chong SL, Ong GY, Allen JC, Lee JH, Piragasam R, Koh GZX, Mahajan P, Liu N, Ong MEH. Early prediction of serious infections in febrile infants incorporating heart rate variability in an emergency department: a pilot study. Emerg Med J. 2021 Aug;38(8):607-612. doi: 10.1136/emermed-2020-210675. Epub 2021 Apr 16.
PubMed 33863774
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rapid Triage for Serious Infections in Infants Younger Than 3 Months Using A Novel Heart Rate Variability Tool
- ClinicalTrials.gov ID
- NCT04103151
- Acronym / sponsor ID
- HRV / HRV-INFANTS-2017
- Conditions
- Heart Rate, Variability, Triage, Decision Support Techniques
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 330 participants (actual)
- Lead sponsor
- KK Women's and Children's HospitalOther government
- Collaborators
- National Medical Research Council (NMRC), Singapore
- Study start
- 11 Dec 2017 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 25 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Febrile infants younger than 3 months old present a diagnostic dilemma to the emergency physician. Tension remains between the need for early aggressive intervention among patients with suspected sepsis and the global phenomena of increasing antibiotic resistance.
The investigators aim to: (1) To study the association between heart rate variability (HRV) and the presence of a serious infection (SI) among infants younger than 3 months old. The investigators hypothesize that a reduced HRV is associated with the presence of SI. (2) To compare HRV between febrile infants < 3 months with non-febrile infants. The investigators hypothesize that the variability will be reduced in febrile infants with SIs when compared to non-febrile well infants, but not among febrile infants without SIs when compared to non-febrile well infants. (3) To study if HRV will provide incremental diagnostic information over current triage tools.
Detailed description
Febrile young infants younger than 3 months old present a diagnostic dilemma to the pediatric emergency department (ED) physician. The potential for a missed serious infection (SI) poses the threat of premature death and long-term disability among these infants. Despite decreasing early-onset neonatal sepsis rates due to obstetric prevention strategies, high rates of hospitalization and administration of parenteral antibiotics occur in this age group. Continual tension remains between the need for early and aggressive intervention among patients suspected with sepsis and the global phenomena of increasing antibiotic resistance. Research networks have attempted to build diagnostic algorithms to guide the identification of these ill infants. These are often useful as adjuncts to the clinician's gestalt, but generalizability remains questionable.
Vital signs are of paramount importance in recognizing ill children and have been used in pediatric early warning system scores (PEWS) and various triage systems. Vital signs have resurfaced as the focus of research in recent years, with various groups purposing to update evidence-based normal heart rate ranges among children. Normative heart rate ranges are infamously difficult to define due to the hemodynamic lability in these young infants, multiple confounders for abnormal heart rate, and the variable physiological response during acute stress states.
Previous pilot data showed that the Advanced Paediatric Life Support (APLS) and Fleming (<10th or >90th centile) guidelines performed with the highest sensitivity (66.0% and 62.6%, respectively) and the highest Negative Predictive Value (NPV) (73.3% and 71.4%, respectively). No single guideline reached a sensitivity of greater than 70%.
Objectives and Hypothesis
- To study the association between heart rate variability (HRV) and the presence of a serious infection (SI) among infants younger than 3 months old. The investigators hypothesize that a reduced HRV is associated with the presence of SI.
- To compare HRV between febrile infants < 3 months with non-febrile infants. The investigators hypothesize that the variability will be reduced in febrile infants with SIs when compared to non-febrile well infants, but not among febrile infants without SIs when compared to non-febrile well infants.
- To study if HRV will provide incremental diagnostic information over current triage tools.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Febrile infants | – | Device: Single lead ECGFebrile Infants less than 3 months presenting to the emergency department with a temperature of ≥ 38oC. |
| Afebrile infants | – | Device: Single lead ECGAfebrile Infants less than 3 months presenting to the emergency department |
Who may qualify
- Ages
- 1 day to 3 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- 330 infants < 3 months presenting with fever. Fever is defined as an axillary or rectal temperature ≥ 38oC. 75 infants < 3 months (clinically well) presenting without fever. These include young infants presenting for neonatal jaundice or other non-febrile conditions.
Key inclusion criteria (1 listed)
- Infants < 3 months presenting to the ED will be included (both febrile and non-febrile) Febrile infants are those with an axillary or rectal temperature ≥ 38oC at triage and/or outside of the hospital. OR Non-febrile infants include those presenting to the ED for serum bilirubin checks or otherwise
Key exclusion criteria (1 listed)
- Infants who are in active resuscitation for septic shock. Infants of parents who refused to give informed consent. Premature infants delivered at a gestation of < 35 weeks.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Single lead ECGHeart Rate Variability will be monitored using a single lead electrocardiogram | Device | Afebrile infants, Febrile infants |
Primary outcome
Number of patients with Serious Infections
Time frame: Within 2 weeks of hospitalisation
Serious infections are defined by: Sepsis, meningitis, lobar pneumonia, osteomyelitis, abscess, and urinary tract infection
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2024.
- Derived from this study: PubMed 40335269Choa ZX, Raveentheran G, Khoo ZX, Ong GY, Wong L, Piragasam R, Ganapathy S, Chong SL. Prevalence of serious bacterial infections and performance of inflammatory markers in febrile infants with and without proven viral illness. Emerg Med J. 2025 Oct 20;42(11):721-727. doi: 10.1136/emermed-2024-214435.
- Derived from this study: PubMed 33863774Chong SL, Ong GY, Allen JC, Lee JH, Piragasam R, Koh GZX, Mahajan P, Liu N, Ong MEH. Early prediction of serious infections in febrile infants incorporating heart rate variability in an emergency department: a pilot study. Emerg Med J. 2021 Aug;38(8):607-612. doi: 10.1136/emermed-2020-210675. Epub 2021 Apr 16.
- Individual participant dataSharing planned: No. Individual participant data will be shared with current study team. Sharing of de-identified data with collaborators will be reviewed by the study team.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Rate and Variability, run by KK Women's and Children's Hospital at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with Serious Infections (time frame: Within 2 weeks of hospitalisation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04103151, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2024.