Diagnostic and Prognostic Biomarkers for Childhood Bacterial Pneumonia
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03996967|
Recruitment Status : Recruiting
First Posted : June 25, 2019
Last Update Posted : June 25, 2019
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.
|Condition or disease|
|Pneumonia, Bacterial Viral Infection Clinical Pneumonia Plasmodium Falciparum Malaria Malaria Infections, Respiratory|
|Study Type :||Observational|
|Estimated Enrollment :||900 participants|
|Official Title:||Diagnostic and Prognostic Biomarkers for Childhood Bacterial Pneumonia in Sub-Saharan Africa|
|Actual Study Start Date :||February 11, 2019|
|Estimated Primary Completion Date :||May 2020|
|Estimated Study Completion Date :||May 2020|
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)
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.
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
- 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.
- Probable bacterial pneumonia (versus viral pneumonia or severe malaria) [ Time Frame: At admission ]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.
- Oxygen saturation curve [ Time Frame: Within the first 5 days of admission ]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
- Need to switch antibiotic therapy [ Time Frame: Within the first 3 days of admission ]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
- Duration of hospital admission [ Time Frame: Within 3 days of hospital discharge ]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.
- Time to start feeding well [ Time Frame: Within the first 5 days of admission ]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
Biospecimen Retention: Samples Without DNA
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03996967
|Contact: Clarissa Valim, MD ScDemail@example.com|
|Contact: Patricia Hibberd, MD PhDfirstname.lastname@example.org|
|United States, Massachusetts|
|Boston University School of Public Health||Active, not recruiting|
|Boston, Massachusetts, United States, 02118|
|Basse Field Station, Medical Research Council Gambia Unit||Recruiting|
|Basse Santa Su, URR, Gambia|
|Contact: Grant Mackenzie 220 5669255/7207826 email@example.com|
|Principal Investigator: Grant Mackenzie, M.D., Ph.D.|
|Sub-Investigator: Umberto D'Alessandro, M.D., Ph.D.|
|Laboratory of Transnational Immunology, UMC Utrecht||Active, not recruiting|
|Utrecht, Netherlands, 3584|
|Principal Investigator:||Clarissa Valim, MD ScD||Boston University|
|Principal Investigator:||Patricia Hibberd, MD PhD||Boston University|