Pneumonia, BacterialNCT03996967
Diagnostic and Prognostic Biomarkers for Childhood Bacterial Pneumonia
An observational study of Pneumonia, Bacterial and Viral Infection, run by Boston University at 3 sites in 3 countries.
Trial summary
Clinical pneumonia is a leading cause of pediatric hospitalization. The etiology is generally bacterial or viral. Prompt and optimal treatment of pneumonia is critical to reduce mortality. Read more about this study
- Who is it for?
- Ages 2 months to 5 years
- Conditions the study is for
- Pneumonia, Bacterial, Viral Infection, Clinical Pneumonia
- How many people
- 837 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 11 Feb 2019to 10 Apr 2021
- 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
- No healthy volunteers
- Child
Study population: This study will be enrolling children 2 month-5 years of age who seek treatment for clinical pneumonia at two hospitals in rural Gambia: Basse and Bansang hospitals
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Pediatric patients aged between 2 months and 5 years presenting at the screening sites with respiratory symptoms, i.e. cough or difficulty breathing AND
- One of the following: Increased respiratory rate for age OR indrawing OR SaO2 < 93% OR grunting OR MUAC < 11.5 if child is greater or equal than 6 months of age OR visible wasting AND
- Referred to clinician review for probable admission
- Definition of increased respiratory rate (rr) for age based on the WHO criteria: respiratory rate (rr) > > 50 for 2-11 month old; rr > 40 for 1-5 years old.
- No symptoms or signs of any disease
- No malaria infection as detected by microscopy or RDT
- No history of clinical pneumonia or hospital admission
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Suspected tuberculosis based on history of cough lasting > 2 weeks
- Hospital admission in the previous 2 weeks.
- Children that show any evidence of other conditions that could be worsened by blood collection will be further excluded from this study.
- Having received a vaccine within the prior 4 weeks
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
United States1 site
Boston University School of Public Health
Boston, Massachusetts, 02118
Netherlands1 site
Laboratory of Transnational Immunology, UMC Utrecht
Utrecht, 3584
The Gambia1 site
Basse Field Station, Medical Research Council Gambia Unit
Basse Santa Su, URR
About this study
Official title: Diagnostic and Prognostic Biomarkers for Childhood Bacterial Pneumonia in Sub-Saharan Africa
Clinical pneumonia is a leading cause of pediatric hospitalization. The etiology is generally bacterial or viral. Prompt and optimal treatment of pneumonia is critical to reduce mortality. However, adequate pneumonia management is hampered by: a) the lack of a diagnostic tool that can be used at point-of-care (POC) and promptly and accurately allow the diagnosis of bacterial disease and b) lack of a prognostic POC test to help triage children in need of intensive assistance. Antibiotic therapy is frequently overprescribed as a result of suspected bacterial infections resulting in development of antibiotic resistance. Conversely, in malaria-endemic areas, antibiotics may also be "underprescribed" and children with bacterial pneumonia sent home without antibiotic therapy, when the clinical pneumonia is mistakenly attributed to a co-existing malaria infection.
The investigators previously identified combinations of protein with 96% sensitivity and 86% specificity for detecting bacterial disease in Mozambican children with clinical pneumonia. The investigators' prior work showed that it is possible to identify biosignatures for diagnosis and prognosis using few proteins. Recently, other authors also identified different accurate biosignatures (e.g., IP-10, TRAIL and CRP).
Read more
In this study, the investigators propose to validate and improve upon previous biosignatures by testing prior combinations and seeking novel combinations of markers in 900 pediatric inpatients aged 2 months to 5 years with clinical pneumonia in The Gambia. The investigators will also use alternative case criteria and seek diagnostic and prognostic combination of markers. This study will be conducted in Basse, rural Gambia, in two hospitals associated with the Medical Research Council Unity The Gambia (MRCG). Approximately 900 pediatric patients with clinical pneumonia aged 2 months to 5 years of age will be enrolled. Patients will undergo standard of care test and will have blood proteins measured through Luminex®-based immunoassays.
Results of this study may ultimately support future development of an accurate point-of-care test for bacterial disease to guide clinicians in choices of treatment and to assist in the prioritization of intensive care in resource-limited settings.
- Conditions
- Pneumonia, Bacterial, Viral Infection, Clinical Pneumonia, Plasmodium Falciparum Malaria, Malaria, Infections, Respiratory
- Keywords
- Biosignature proteins, Luminex®-based immunoassays, Point-of-care test, Children, Sub-Saharan Africa, Diagnostic Biomarkers, Prognostic Biomarkers, Mediators of Inflammation
- Medical subject headings
- Pneumonia, Bacterial, Virus Diseases, Malaria, Falciparum, Malaria, Respiratory Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| BA Group | The bacterial group: Patients will be assorted to this group if he/she has a bacterial pathogen culture of fluid from a normally sterile site (e.g. blood, pleural fluid) | |
| VI Group | The viral group: Patients will be assigned to this group if they have negative bacteria microbiological tests, negative malaria blood slides, X-rays without "endpoint pneumonia", no evidence of fungal infection, and positive PCR for a viral pathogen from nasopharyngeal swabs. | |
| MA Group | The malarial group: Patients will be assigned to this group if they have normal X-rays, no bacterial infection and >0 asexual P. falciparum parasites if they are aged < 1 year, or > 2,500 asexual parasites/µl of blood if they are aged > 1 year |
What is being measured
The primary outcome is the main question the study is designed to answer.
Definitive diagnosis of an invasive bacterial disease (versus viral and malarial infection)
A patient will be assigned to the bacterial (BA) group if he/she has a bacterial pathogen culture of fluid from a normally sterile site (e.g. blood, pleural fluid). Patients will be assigned to the viral (VI) group if they have negative bacteria microbiological tests, negative malaria blood slides, X-ray without "endpoint pneumonia" (consolidation or pleural effusion50), no evidence of fungal infection, and positive PCR for a viral pathogen from nasopharyngeal swabs. Patients will be assigned to the malarial (MA) group if they have normal X-ray (with neither infiltrates nor endpoint pneumonia), no bacterial infection and > 0 asexual P. falciparum parasites if they are aged < 1 year, or > 2,500 asexual parasites/µl of blood if they are aged > 1 year. Patients who are admitted with viral infections but who develop bacterial pneumonia during hospitalization will be excluded from VI
Measured: At admission
Poor prognosis of clinical pneumonia
Patients will be categorized in the following three groups based on a review of clinical records: a) children who die during or within the first 30 days from admission (all children that meet this criteria), b) children with prolonged hospital stay or who need to have antibiotic therapy changed within 48 hours of admission or who were re-admitted within 30 days from the first admission; and c) children discharged well within 3 days of admission and without the need for a change in antibiotic therapy after admission.
Measured: 30 days from admission
Secondary outcomes (5)
Probable bacterial pneumonia (versus viral pneumonia or severe malaria)
Based on the review of data by an expert panel, patients will be assigned to either: a) the probable bacterial group (BA) or the b) non bacterial group. Data to be reviewed by the panel will include chest X-ray, complete blood cell counts, other laboratory results, the clinical course during admission and following discharge. Children will be assigned to the non bacterial group (i.e, VI or MA) if they have X-ray without endpoint pneumonia, pleural effusion or infiltrates, do not have bacterial infection as per the algorithm for definitive diagnosis and are not classified as bacterial infection by the expert panel.
Measured: At admission
Oxygen saturation curve
Area under the first five days of the oxygen saturation curve. Oxygen saturation will be recorded daily in the morning in a follow-up form
Measured: Within the first 5 days of admission
Need to switch antibiotic therapy
All patients will be classified as either needing or not needing to switch within the first three days of hospitalization their antibiotic therapy prescribed at admission based on a follow-up form
Measured: Within the first 3 days of admission
Duration of hospital admission
The total length of hospital admission will be calculated in days for each patient based on the difference between the dates of discharge and admission.
Measured: Within 3 days of hospital discharge
Time to start feeding well
Time to feed well will be defined based on the child examination in the morning within the first 5 days of follow-up that will be recorded in a follow-up form
Measured: Within the first 5 days of admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2019
- Study start11 Feb 2019
- Primary completion10 Apr 2021
- Study completion10 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pneumonia, BacterialStudies of the same condition, open and under way.
- More trials run by Boston UniversityThe 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 837 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Medical Research Council Unit, The Gambia, Laboratory of Transnational Immunology, UMC Utrecht
- Responsible party
- Sponsor
- Investigators
- Clarissa Valim, MD ScD, Principal investigator, Boston UniversityPatricia Hibberd, MD PhD, Principal investigator, Boston University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03996967
- Sponsor's protocol ID
- H-38462
- Other IDs
- R21AI140258-01
- Status last verified
- May 2022
- First submitted
- 20 Jun 2019
- Last updated
- 31 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diagnostic and Prognostic Biomarkers for Childhood Bacterial Pneumonia in Sub-Saharan Africa
- ClinicalTrials.gov ID
- NCT03996967
- Acronym / sponsor ID
- H-38462
- Conditions
- Pneumonia, Bacterial, Viral Infection, Clinical Pneumonia, Plasmodium Falciparum Malaria, Malaria, Infections, Respiratory
- Keywords
- Biosignature proteins, Luminex®-based immunoassays, Point-of-care test, Children, Sub-Saharan Africa, Diagnostic Biomarkers, Prognostic Biomarkers, Mediators of Inflammation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 837 participants (actual)
- Lead sponsor
- Boston UniversityUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Medical Research Council Unit, The Gambia, Laboratory of Transnational Immunology, UMC Utrecht
- Study start
- 11 Feb 2019 (actual)
- Primary completion
- 10 Apr 2021 (actual)
- Study completion
- 10 Apr 2021 (actual)
- First posted
- 25 Jun 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.
Clinical pneumonia is a leading cause of pediatric hospitalization. The etiology is generally bacterial or viral. Prompt and optimal treatment of pneumonia is critical to reduce mortality. However, adequate pneumonia management is hampered by: a) the lack of a diagnostic tool that can be used at point-of-care (POC) and promptly and accurately allow the diagnosis of bacterial disease and b) lack of a prognostic POC test to help triage children in need of intensive assistance. Antibiotic therapy is frequently overprescribed as a result of suspected bacterial infections resulting in development of antibiotic resistance. Conversely, in malaria-endemic areas, antibiotics may also be "underprescribed" and children with bacterial pneumonia sent home without antibiotic therapy, when the clinical pneumonia is mistakenly attributed to a co-existing malaria infection.
The investigators previously identified combinations of protein with 96% sensitivity and 86% specificity for detecting bacterial disease in Mozambican children with clinical pneumonia. The investigators' prior work showed that it is possible to identify biosignatures for diagnosis and prognosis using few proteins. Recently, other authors also identified different accurate biosignatures (e.g., IP-10, TRAIL and CRP).
In this study, the investigators propose to validate and improve upon previous biosignatures by testing prior combinations and seeking novel combinations of markers in 900 pediatric inpatients aged 2 months to 5 years with clinical pneumonia in The Gambia. The investigators will also use alternative case criteria and seek diagnostic and prognostic combination of markers. This study will be conducted in Basse, rural Gambia, in two hospitals associated with the Medical Research Council Unity The Gambia (MRCG). Approximately 900 pediatric patients with clinical pneumonia aged 2 months to 5 years of age will be enrolled. Patients will undergo standard of care test and will have blood proteins measured through Luminex®-based immunoassays.
Results of this study may ultimately support future development of an accurate point-of-care test for bacterial disease to guide clinicians in choices of treatment and to assist in the prioritization of intensive care in resource-limited settings.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| BA Group | – | –The bacterial group: Patients will be assorted to this group if he/she has a bacterial pathogen culture of fluid from a normally sterile site (e.g. blood, pleural fluid) |
| VI Group | – | –The viral group: Patients will be assigned to this group if they have negative bacteria microbiological tests, negative malaria blood slides, X-rays without "endpoint pneumonia", no evidence of fungal infection, and positive PCR for a viral pathogen from nasopharyngeal swabs. |
| MA Group | – | –The malarial group: Patients will be assigned to this group if they have normal X-rays, no bacterial infection and >0 asexual P. falciparum parasites if they are aged < 1 year, or > 2,500 asexual parasites/µl of blood if they are aged > 1 year |
Who may qualify
- Ages
- 2 months to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- This study will be enrolling children 2 month-5 years of age who seek treatment for clinical pneumonia at two hospitals in rural Gambia: Basse and Bansang hospitals
Key inclusion criteria (8 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Pediatric patients aged between 2 months and 5 years presenting at the screening sites with respiratory symptoms, i.e. cough or difficulty breathing AND
- One of the following: Increased respiratory rate for age OR indrawing OR SaO2 < 93% OR grunting OR MUAC < 11.5 if child is greater or equal than 6 months of age OR visible wasting AND
- Referred to clinician review for probable admission
- Definition of increased respiratory rate (rr) for age based on the WHO criteria: respiratory rate (rr) > > 50 for 2-11 month old; rr > 40 for 1-5 years old.
Key exclusion criteria (5 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Suspected tuberculosis based on history of cough lasting > 2 weeks
- Hospital admission in the previous 2 weeks.
- Children that show any evidence of other conditions that could be worsened by blood collection will be further excluded from this study.
- Having received a vaccine within the prior 4 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Definitive diagnosis of an invasive bacterial disease (versus viral and malarial infection)
Time frame: At admission
A patient will be assigned to the bacterial (BA) group if he/she has a bacterial pathogen culture of fluid from a normally sterile site (e.g. blood, pleural fluid). Patients will be assigned to the viral (VI) group if they have negative bacteria microbiological tests, negative malaria blood slides, X-ray without "endpoint pneumonia" (consolidation or pleural effusion50), no evidence of fungal infection, and positive PCR for a viral pathogen from nasopharyngeal swabs. Patients will be assigned to the malarial (MA) group if they have normal X-ray (with neither infiltrates nor endpoint pneumonia), no bacterial infection and > 0 asexual P. falciparum parasites if they are aged < 1 year, or > 2,500 asexual parasites/µl of blood if they are aged > 1 year. Patients who are admitted with viral infections but who develop bacterial pneumonia during hospitalization will be excluded from VI
Poor prognosis of clinical pneumonia
Time frame: 30 days from admission
Patients will be categorized in the following three groups based on a review of clinical records: a) children who die during or within the first 30 days from admission (all children that meet this criteria), b) children with prolonged hospital stay or who need to have antibiotic therapy changed within 48 hours of admission or who were re-admitted within 30 days from the first admission; and c) children discharged well within 3 days of admission and without the need for a change in antibiotic therapy after admission.
5 secondary outcomes
Probable bacterial pneumonia (versus viral pneumonia or severe malaria)
Time frame: At admission
Oxygen saturation curve
Time frame: Within the first 5 days of admission
Need to switch antibiotic therapy
Time frame: Within the first 3 days of admission
Duration of hospital admission
Time frame: Within 3 days of hospital discharge
Time to start feeding well
Time frame: Within the first 5 days of 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 31 May 2022.
- Individual participant dataSharing planned: No
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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.
Clarissa Valim, MD ScD principal investigator
Boston University
Patricia Hibberd, MD PhD principal investigator
Boston University
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pneumonia, Bacterial and Viral Infection, run by Boston University at 3 sites in 3 countries.
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 8 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 31 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Netherlands, The Gambia. 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?
Definitive diagnosis of an invasive bacterial disease (versus viral and malarial infection) (time frame: At admission). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 May 2022.