Ignite Creation Date:
2024-05-06 @ 4:18 PM
Last Modification Date:
2024-10-26 @ 2:08 PM
Study NCT ID:
NCT04944719
Status:
UNKNOWN
Last Update Posted:
2021-06-30
First Post:
2021-06-10
Brief Title:
Pneumococcal Nasopharyngeal Colonization as Predictor of Community-Acquired Pneumonia CAP in Adults With Chronic Diseases
Sponsor:
Universidad de la Sabana
Organization:
Universidad de la Sabana
Study Overview
Official Title:
Pneumococcal Nasopharyngeal Colonization as Predictor of Community-Acquired Pneumonia in Adults With Chronic Diseases A Real-word Evidence Prospective Observational Multicenter Cohort Study
Status:
UNKNOWN
Status Verified Date:
2021-06
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CAP
Brief Summary:
Streptococcus pneumoniae pneumococcus is a commensal bacterium often isolated in the nasopharynx of preschool children and older adults with weakened immune systems a pathogen that remains the leading cause of Community-Acquired Pneumonia CAP and invasive pneumococcal disease IPD such as Sepsis and Meningitis
CAP is the sixth leading cause of overall mortality and the first cause of infectious disease in Colombia and the world Montúfar et al 2013 GBD 2016 WHO 2018 and both its incidence and prevalence have remained stable over the past 3 decades Likewise CAP due to S pnemoniae is the most common cause of lower respiratory tract infections in humans worldwide and is associated with high morbidity and mortality in patients who suffer from it
Pneumococcus frequently colonizes the nasopharynx of children and adults and therefore this condition has been postulated as a risk factor for the development of CAP There are reports of the effect of nasopharyngeal colonization in infants but the implications of this colonization in adults especially adults with chronic comorbidities are not known
Additionally several studies point to a relationship between pathogenicity colonization capacity and disease severity according to the infecting pneumococcal serotype Therefore it is not known which pneumococcal serotypes are most frequently colonized by adults with chronic diseases cardiovascular disease CVD chronic obstructive pulmonary disease COPD renal disease RHD rheumatological disease MDR Diabetes Mellitus DM among others and the potential clinical implications of this colonization
For these reasons this research aims to study the phenomenon of colonization by pneumococcus in patients with chronic diseases for the development of CAP and the relationship between the virulence genes of different serotypes and the outcome in invasive pneumococcal disease IPD
This study is based on real evidence from clinical practice and translational medicine is prospective-observational multicenter and cohort type in consecutive patients Thus in a first phase the clinical observation of the subjects will be carried out a second phase of follow-up and sampling in the patients and a third phase of molecular analysis
CAP is the sixth leading cause of overall mortality and the first cause of infectious disease in Colombia and the world Montúfar et al 2013 GBD 2016 WHO 2018 and both its incidence and prevalence have remained stable over the past 3 decades Likewise CAP due to S pnemoniae is the most common cause of lower respiratory tract infections in humans worldwide and is associated with high morbidity and mortality in patients who suffer from it
Pneumococcus frequently colonizes the nasopharynx of children and adults and therefore this condition has been postulated as a risk factor for the development of CAP There are reports of the effect of nasopharyngeal colonization in infants but the implications of this colonization in adults especially adults with chronic comorbidities are not known
Additionally several studies point to a relationship between pathogenicity colonization capacity and disease severity according to the infecting pneumococcal serotype Therefore it is not known which pneumococcal serotypes are most frequently colonized by adults with chronic diseases cardiovascular disease CVD chronic obstructive pulmonary disease COPD renal disease RHD rheumatological disease MDR Diabetes Mellitus DM among others and the potential clinical implications of this colonization
For these reasons this research aims to study the phenomenon of colonization by pneumococcus in patients with chronic diseases for the development of CAP and the relationship between the virulence genes of different serotypes and the outcome in invasive pneumococcal disease IPD
This study is based on real evidence from clinical practice and translational medicine is prospective-observational multicenter and cohort type in consecutive patients Thus in a first phase the clinical observation of the subjects will be carried out a second phase of follow-up and sampling in the patients and a third phase of molecular analysis
Detailed Description:
Streptococcus pneumoniae the pneumococcus is responsible for more than 5 million deaths a year globally Aliberti et al 2016 Reyes et al 2017 This opportunistic Gram-positive bacterium is the most frequently identified bacteria in patients with CAP acute meningitis and otitis in children and adults Paterson et al 2010 Hinojosa et al 2014
The pneumococcal disease has changed during the last decade due to universal pneumococcal vaccination programs especially in children patients with chronic pulmonary diseases and patients older than 65 years old Now serotypes thought to be not clinically significant are frequently identified in patients with pneumococcal diseases Imohl et al 2015 Vlachopoulos et al 2015 Cilloniz et al 2016 Diao et al 2016 Suzuki et al 2017
However mortality and morbidity associated with pneumococcal infection in adults have remained relatively steady during the last decades Jain et al 2015 Bellew et al 2018 Wunderink et al 2018 Several hypotheses have been generated to explain this phenomenon Among the most studied researchers have documentedthat circulating pneumococcal serotypes are different now and thus currently available vaccines may not be as useful to prevent invasive pneumococcal diseases now Aliberti et al 2013 Cilloniz et al 2016
Moreover adults are not frequently vaccinated with the pneumococcal vaccine and only a very restrictive group of patients receive the vaccine In Colombia it is not known whether even that restrictive group of adults with an indication for a pneumococcal vaccine have been vaccinated following national and international guidelines More importantly it is unknown whether other groups of patients with chronic medical diseases might benefit from receiving this vaccine
Importantly it is also unknown which are the most prevalent serotypes causing colonization and invasive infections in adults with chronic diseases in Colombia
We have recently carried out a multicenter multinational worldwide study designed to characterize better the etiology of CAP the most frequent infection caused by the pneumococcus Aliberti et al 2016 Carugati et al 2016 Gramegna et al 2018 Restrepo et al 2018 Radovanovic et al 2019
In this study we enrolled more than 3700 patients in six continents finding that S pneumoniae continues to be the most frequent bacterial pathogen identified in patients with CAP worldwide However in this study we also documented that the pneumococcal vaccination rate is meager data not yet published Thus we firmly believe that identifying whether pneumococcal vaccination is adequate in our country Colombia and more importantly which are the most prevalent pneumococcal serotypes colonizing the nasopharyngeal epithelium of patients with chronic medical conditions might help us to identify new indications for pneumococcal vaccination and to help decrease the burden of pneumococcal diseases
Therefore here we will attempt to provide new information to characterize better pneumococcal nasopharyngeal colonization of patients with chronic medical diseases its implications its overtime dynamics and how this colonization might be associated with CPA development Moreover here we will be able to characterize vaccination compliance and how this previous vaccination might modify the natural course of pneumococcal disease ie nasopharyngeal colonization precedes pneumococcal pneumonia Finally here we will carry out real-world evidence prospective study evidence that will provide generalizable data for clinicians around the globe
This is real-world evidence prospective observational multicenter a cohort study of consecutive patients
Inclusion Criteria
All consecutive ambulatory patients that assist to 5 outpatient clinics with chronic diseases such as heart failure HBP chronic cardiac arrhythmias rheumatic diseases non-cystic-fibrosis bronchiectasis COPD among others with the following inclusion criteria will be included in the study
Older than 18 years old
Patients assisting to cardiology pulmonology endocrinology or rheumatology clinic in participating centers
Patients in whom vaccination information is available and confirmed in the medical records this information will also be confirmed during the patients interview
Patients that sign informed consent form
Exclusion Criteria
Patients diagnosed with CAP during the past 90 days
Patients admitted to the hospital during the last 7 days
Patients with limitation to provide biological samples
Baseline procedures
After identifying potential study subjects informed consent will be obtained for interested patients and a unique identification number will be assigned for each study participant Under any circumstance patients will receive more than one identification number Then demographic data past medical history comorbid conditions recent hospitalization and biological samples will be gathered
We will perform a nasopharyngeal swap to identify which patients are colonized with S pneumoniae and to identify which are the most prevalent pneumococcal serotypes We will draw 20cc of blood to identify inflammatory biomarkers and 30cc urine samples will be collected for laboratory analyses
Biological samples processing
After collecting samples in ambulatory clinics during study visits these will be referred to our centralized research laboratory localized in the Universidad de La Sabana to carry out laboratory experiments All nasopharyngeal swaps will be culture for pneumococcal identification if S pneumoniae is identified we will characterize in our laboratory pneumococcal serotypes Moreover we will perform rtPCR to better identify and quantify pneumococcal colonization in the nasopharyngeal swabs
We will also quantify serum biomarkers of inflammation using commercially available ELISA kits Importantly all laboratory personnel will be blinded to patients characteristics and clinical outcomes to ensure data quality and avoid observer bias
Follow-ups and outcome determination
As the primary aim of this study is to determine the role of nasopharyngeal colonization in the development of CAP or IPD after identifying patients colonized by S pneumoniae during baseline experiments patients will be followed every month by phone and every 6 months in our outpatient clinics to identify patients that develop CAP or IPD
Patients will be asked to report any hospital visit ER visit hospital admission and ICU admission to the study coordinator and to bring discharge summaries provided by hospitals Patients will be a follow-up for 2 consecutive years During follow-ups sample collection will be performed to determine whether patients develop nasopharyngeal colonization or change its systemic inflammatory profile Samples will be collected and analyzed as baseline procedures
The pneumococcal disease has changed during the last decade due to universal pneumococcal vaccination programs especially in children patients with chronic pulmonary diseases and patients older than 65 years old Now serotypes thought to be not clinically significant are frequently identified in patients with pneumococcal diseases Imohl et al 2015 Vlachopoulos et al 2015 Cilloniz et al 2016 Diao et al 2016 Suzuki et al 2017
However mortality and morbidity associated with pneumococcal infection in adults have remained relatively steady during the last decades Jain et al 2015 Bellew et al 2018 Wunderink et al 2018 Several hypotheses have been generated to explain this phenomenon Among the most studied researchers have documentedthat circulating pneumococcal serotypes are different now and thus currently available vaccines may not be as useful to prevent invasive pneumococcal diseases now Aliberti et al 2013 Cilloniz et al 2016
Moreover adults are not frequently vaccinated with the pneumococcal vaccine and only a very restrictive group of patients receive the vaccine In Colombia it is not known whether even that restrictive group of adults with an indication for a pneumococcal vaccine have been vaccinated following national and international guidelines More importantly it is unknown whether other groups of patients with chronic medical diseases might benefit from receiving this vaccine
Importantly it is also unknown which are the most prevalent serotypes causing colonization and invasive infections in adults with chronic diseases in Colombia
We have recently carried out a multicenter multinational worldwide study designed to characterize better the etiology of CAP the most frequent infection caused by the pneumococcus Aliberti et al 2016 Carugati et al 2016 Gramegna et al 2018 Restrepo et al 2018 Radovanovic et al 2019
In this study we enrolled more than 3700 patients in six continents finding that S pneumoniae continues to be the most frequent bacterial pathogen identified in patients with CAP worldwide However in this study we also documented that the pneumococcal vaccination rate is meager data not yet published Thus we firmly believe that identifying whether pneumococcal vaccination is adequate in our country Colombia and more importantly which are the most prevalent pneumococcal serotypes colonizing the nasopharyngeal epithelium of patients with chronic medical conditions might help us to identify new indications for pneumococcal vaccination and to help decrease the burden of pneumococcal diseases
Therefore here we will attempt to provide new information to characterize better pneumococcal nasopharyngeal colonization of patients with chronic medical diseases its implications its overtime dynamics and how this colonization might be associated with CPA development Moreover here we will be able to characterize vaccination compliance and how this previous vaccination might modify the natural course of pneumococcal disease ie nasopharyngeal colonization precedes pneumococcal pneumonia Finally here we will carry out real-world evidence prospective study evidence that will provide generalizable data for clinicians around the globe
This is real-world evidence prospective observational multicenter a cohort study of consecutive patients
Inclusion Criteria
All consecutive ambulatory patients that assist to 5 outpatient clinics with chronic diseases such as heart failure HBP chronic cardiac arrhythmias rheumatic diseases non-cystic-fibrosis bronchiectasis COPD among others with the following inclusion criteria will be included in the study
Older than 18 years old
Patients assisting to cardiology pulmonology endocrinology or rheumatology clinic in participating centers
Patients in whom vaccination information is available and confirmed in the medical records this information will also be confirmed during the patients interview
Patients that sign informed consent form
Exclusion Criteria
Patients diagnosed with CAP during the past 90 days
Patients admitted to the hospital during the last 7 days
Patients with limitation to provide biological samples
Baseline procedures
After identifying potential study subjects informed consent will be obtained for interested patients and a unique identification number will be assigned for each study participant Under any circumstance patients will receive more than one identification number Then demographic data past medical history comorbid conditions recent hospitalization and biological samples will be gathered
We will perform a nasopharyngeal swap to identify which patients are colonized with S pneumoniae and to identify which are the most prevalent pneumococcal serotypes We will draw 20cc of blood to identify inflammatory biomarkers and 30cc urine samples will be collected for laboratory analyses
Biological samples processing
After collecting samples in ambulatory clinics during study visits these will be referred to our centralized research laboratory localized in the Universidad de La Sabana to carry out laboratory experiments All nasopharyngeal swaps will be culture for pneumococcal identification if S pneumoniae is identified we will characterize in our laboratory pneumococcal serotypes Moreover we will perform rtPCR to better identify and quantify pneumococcal colonization in the nasopharyngeal swabs
We will also quantify serum biomarkers of inflammation using commercially available ELISA kits Importantly all laboratory personnel will be blinded to patients characteristics and clinical outcomes to ensure data quality and avoid observer bias
Follow-ups and outcome determination
As the primary aim of this study is to determine the role of nasopharyngeal colonization in the development of CAP or IPD after identifying patients colonized by S pneumoniae during baseline experiments patients will be followed every month by phone and every 6 months in our outpatient clinics to identify patients that develop CAP or IPD
Patients will be asked to report any hospital visit ER visit hospital admission and ICU admission to the study coordinator and to bring discharge summaries provided by hospitals Patients will be a follow-up for 2 consecutive years During follow-ups sample collection will be performed to determine whether patients develop nasopharyngeal colonization or change its systemic inflammatory profile Samples will be collected and analyzed as baseline procedures
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None