FeverNCT04726826
Biomarkers of Mortality and Morbidity in Children Hospitalized With Fever
An observational study of Fever, run by University of Alberta at 1 site in Uganda.
Trial summary
The objective of this study is to identify clinically informative biomarkers of host defense pathways with potential utility as diagnostic and prognostic tools among children hospitalized with acute febrile illness in a resource-constrained sub-Saharan African setting. Read more about this study
- Who is it for?
- Ages 2 months to 5 years
- Conditions the study is for
- Fever
- What is being tested?
- Diagnostic and prognostic biomarkers
- How many people
- 2,500 participants
- Where
- 1 siteUganda
- Study dates
- 1 Feb 2012to 15 Sep 2013
- 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 2 months to 5 years
- All sexes
- Child
Study population: The choice of the age range for this study is as follows. Children under 5 represent a vulnerable group, in whom infectious diseases play a major role as contributors to overall mortality. Children under 2 months of age (the neonatal group) represent a unique population with different infectious risks and are therefore outside the scope of our current study. The reason for exclusion of isolated diarrheal illness is that dehydration, acidosis and electrolyte imbalances are the proximal causes of mortality, rather than activation of host defense pathways with excessive inflammation and endothelial activation. Host biomarkers are therefore not expected to predict mortality with the same accuracy in diarrhea syndromes.
Who may be able to join
- Age 2 months to 5 years
- History of fever within past 48 hours or axillary temperature >37.5°C
- Hospital admission warranted based on clinician judgment
- Consent to blood sampling and data collection
Who cannot join
- Outside eligible age range
- No history or objective evidence of fever
- Diarrheal illness without other symptoms
- Outpatient management
- Denial of consent to participate in study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Predictive Biomarkers of Mortality and Morbidity in Children Hospitalized for Acute Febrile Illness
The objective of this study is to identify clinically informative biomarkers of host defense pathways with potential utility as diagnostic and prognostic tools among children hospitalized with acute febrile illness in a resource-constrained sub-Saharan African setting.
The working hypothesis is that a panel of biomarkers, readily measurable from a peripheral blood sample, may serve as a clinically useful instrument to distinguish between common pediatric causes of fever, predict those children at greatest need of aggressive supportive care and/or adjunctive therapies, and identify those children at greatest risk of mortality. The use of objective and quantitative tools may facilitate the triage and clinical care of febrile children admitted to hospital in the sub-Saharan African context.
Read the detailed description
For pediatric patients presenting to Jinja Regional Referral Hospital in whom admission to hospital is deemed necessary by an attending physician, the parent or guardian will be approached for consent to participate in the study. If granted, a small volume (1mL) of blood will be withdrawn for processing and storage. A RDT for malaria and whole blood lactate level will be performed at the bedside. Basic demographic and clinical data will be collected from the case admission record, and patients will be followed during their hospital admission. Possible outcomes will include: death, discharge without disability, discharge with disability, abscondment, and loss to follow-up. The length of stay among survivors will be recorded (excluding patients leaving against medical advice).
Serum samples will be shipped to the collaborating laboratory in Canada for analysis for biomarkers. ELISA-based commercially-available assays for biomarker levels will be used to quantify biomarker levels. In order to measure levels of 13 biomarkers from a plasma sample of 500uL or less, highly co-ordinated procedures with experienced technicians are required to perform the ELISA. Our laboratory in Canada has established protocols, experienced staff able to perform the testing, as well as equipment and reagents allowing the testing to be done efficiently. While it would be desirable to augment Ugandan capacity for biomarker testing, this would require significant investment of time and resources for training and testing, and may not be feasible in the context of this early study. If biomarkers can be identified that have clinical utility, laboratory capacity for ELISA measurement of levels should be developed or a simplified platform (e.g., lateral flow immunochromatographic test) should be developed.
Pneumonia and meningitis will be diagnosed clinically. A combination of tachypnea, respiratory distress (nasal flaring, intercostal and/or subcostal indrawing, or cyanosis) and characteristic findings on chest auscultation (asymmetrical air entry, crackles, dullness to percussion) will be used to make a clinical diagnosis of pneumonia. In our setting, chest x-ray is not available on site and radiographic confirmation will not be routinely available. Neck stiffness, positive Kernig's or Brudzinsky's signs, convulsions and coma will be used to make a diagnosis of meningitis. Where a lumbar puncture is performed, according to clinical judgment, the results will be used to complement clinical diagnosis. CSF pleiocytosis or a positive CSF culture for recognized pathogens will be used to support the diagnosis of meningitis.
- Conditions
- Fever
- Being tested
- Diagnostic and prognostic biomarkers
- Keywords
- fever, child, biomarker
- Medical subject headings
- Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diagnostic and prognostic biomarkersDiagnostic test
Observational study of biomarkers predictive of morbidity and mortality in febrile children
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
in-hospital mortality
Measured: through study completion, an average of 1 week
Secondary outcomes (3)
Hospital length of stay
time from admission to discharge
Measured: through study completion, an average of 1 week
Lambarene organ dysfunction score (LODS), a composite clinical severity score
clinical severity score
Measured: evaluated at admission
Signs of Inflammation in Children that Kill (SICK), a composite clinical severity score
clinical severity score
Measured: evaluated at admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2021
- Study start1 Feb 2012
- Primary completion15 Sep 2013
- Study completion15 Sep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for FeverStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe 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
- 2,500 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- University of Toronto, Global Health Uganda LTD
- Responsible party
- Sponsor
- Investigators
- Michael T Hawkes, MD, PhD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04726826
- Sponsor's protocol ID
- Pro00106489
- Status last verified
- Jan 2021
- First submitted
- 19 Jan 2021
- Last updated
- 27 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be shared upon reasonable request to study prinicipal investigator.
Publications
McDonald CR, Leligdowicz A, Conroy AL, Weckman AM, Richard-Greenblatt M, Ngai M, Erice C, Zhong K, Namasopo S, Opoka RO, Hawkes MT, Kain KC. Immune and endothelial activation markers and risk stratification of childhood pneumonia in Uganda: A secondary analysis of a prospective cohort study. PLoS Med. 2022 Jul 13;19(7):e1004057. doi: 10.1371/journal.pmed.1004057. eCollection 2022 Jul.
PubMed 35830474
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predictive Biomarkers of Mortality and Morbidity in Children Hospitalized for Acute Febrile Illness
- ClinicalTrials.gov ID
- NCT04726826
- Acronym / sponsor ID
- Pro00106489
- Conditions
- Fever
- Keywords
- fever, child, biomarker
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,500 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Collaborators
- University of Toronto, Global Health Uganda LTD
- Study start
- 1 Feb 2012 (actual)
- Primary completion
- 15 Sep 2013 (actual)
- Study completion
- 15 Sep 2013 (actual)
- First posted
- 27 Jan 2021 (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.
The objective of this study is to identify clinically informative biomarkers of host defense pathways with potential utility as diagnostic and prognostic tools among children hospitalized with acute febrile illness in a resource-constrained sub-Saharan African setting.
The working hypothesis is that a panel of biomarkers, readily measurable from a peripheral blood sample, may serve as a clinically useful instrument to distinguish between common pediatric causes of fever, predict those children at greatest need of aggressive supportive care and/or adjunctive therapies, and identify those children at greatest risk of mortality. The use of objective and quantitative tools may facilitate the triage and clinical care of febrile children admitted to hospital in the sub-Saharan African context.
Detailed description
For pediatric patients presenting to Jinja Regional Referral Hospital in whom admission to hospital is deemed necessary by an attending physician, the parent or guardian will be approached for consent to participate in the study. If granted, a small volume (1mL) of blood will be withdrawn for processing and storage. A RDT for malaria and whole blood lactate level will be performed at the bedside. Basic demographic and clinical data will be collected from the case admission record, and patients will be followed during their hospital admission. Possible outcomes will include: death, discharge without disability, discharge with disability, abscondment, and loss to follow-up. The length of stay among survivors will be recorded (excluding patients leaving against medical advice).
Serum samples will be shipped to the collaborating laboratory in Canada for analysis for biomarkers. ELISA-based commercially-available assays for biomarker levels will be used to quantify biomarker levels. In order to measure levels of 13 biomarkers from a plasma sample of 500uL or less, highly co-ordinated procedures with experienced technicians are required to perform the ELISA. Our laboratory in Canada has established protocols, experienced staff able to perform the testing, as well as equipment and reagents allowing the testing to be done efficiently. While it would be desirable to augment Ugandan capacity for biomarker testing, this would require significant investment of time and resources for training and testing, and may not be feasible in the context of this early study. If biomarkers can be identified that have clinical utility, laboratory capacity for ELISA measurement of levels should be developed or a simplified platform (e.g., lateral flow immunochromatographic test) should be developed.
Pneumonia and meningitis will be diagnosed clinically. A combination of tachypnea, respiratory distress (nasal flaring, intercostal and/or subcostal indrawing, or cyanosis) and characteristic findings on chest auscultation (asymmetrical air entry, crackles, dullness to percussion) will be used to make a clinical diagnosis of pneumonia. In our setting, chest x-ray is not available on site and radiographic confirmation will not be routinely available. Neck stiffness, positive Kernig's or Brudzinsky's signs, convulsions and coma will be used to make a diagnosis of meningitis. Where a lumbar puncture is performed, according to clinical judgment, the results will be used to complement clinical diagnosis. CSF pleiocytosis or a positive CSF culture for recognized pathogens will be used to support the diagnosis of meningitis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 2 months to 5 years
- Sex
- All
- Age groups
- Child
- Study population
- The choice of the age range for this study is as follows. Children under 5 represent a vulnerable group, in whom infectious diseases play a major role as contributors to overall mortality. Children under 2 months of age (the neonatal group) represent a unique population with different infectious risks and are therefore outside the scope of our current study. The reason for exclusion of isolated diarrheal illness is that dehydration, acidosis and electrolyte imbalances are the proximal causes of mortality, rather than activation of host defense pathways with excessive inflammation and endothelial activation. Host biomarkers are therefore not expected to predict mortality with the same accuracy in diarrhea syndromes.
Key inclusion criteria (4 listed)
- Age 2 months to 5 years
- History of fever within past 48 hours or axillary temperature >37.5°C
- Hospital admission warranted based on clinician judgment
- Consent to blood sampling and data collection
Key exclusion criteria (5 listed)
- Outside eligible age range
- No history or objective evidence of fever
- Diarrheal illness without other symptoms
- Outpatient management
- Denial of consent to participate in study
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 |
|---|---|---|
| Diagnostic and prognostic biomarkersObservational study of biomarkers predictive of morbidity and mortality in febrile children | Diagnostic test | – |
Primary outcome
Mortality
Time frame: through study completion, an average of 1 week
in-hospital mortality
3 secondary outcomes
Hospital length of stay
Time frame: through study completion, an average of 1 week
Lambarene organ dysfunction score (LODS), a composite clinical severity score
Time frame: evaluated at admission
Signs of Inflammation in Children that Kill (SICK), a composite clinical severity score
Time frame: evaluated at admission
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 27 Jan 2021.
- Derived from this study: PubMed 35830474McDonald CR, Leligdowicz A, Conroy AL, Weckman AM, Richard-Greenblatt M, Ngai M, Erice C, Zhong K, Namasopo S, Opoka RO, Hawkes MT, Kain KC. Immune and endothelial activation markers and risk stratification of childhood pneumonia in Uganda: A secondary analysis of a prospective cohort study. PLoS Med. 2022 Jul 13;19(7):e1004057. doi: 10.1371/journal.pmed.1004057. eCollection 2022 Jul.
- Individual participant dataSharing planned: Yes. Data will be shared upon reasonable request to study prinicipal investigator.
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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.
Michael T Hawkes, MD, PhD principal investigator
University of Alberta
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 Fever, run by University of Alberta at 1 site in Uganda.
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 4 inclusion and 5 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 27 Jan 2021. 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 Uganda. 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?
Mortality (time frame: through study completion, an average of 1 week). 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 NCT04726826, which also lists 1 linked publication.
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 27 Jan 2021; AzTrials last refreshed its copy on 8 Nov 2026.