Severe Infection and Non-injury DeathNCT04012190
SEPSIS Observational Cohort Study in Young Infants in Bangladesh
An observational study of Severe Infection and Non-injury Death, run by The Hospital for Sick Children at 2 sites in Bangladesh.
Trial summary
Globally, infectious diseases such as sepsis, meningitis and pneumonia are among the leading causes of neonatal deaths. A recent observational study in South Asia highlighted the contribution of both bacterial and viral infections to the burden of illness in infants <60 days of age; however, there remains a need to… Read more about this study
- Who is it for?
- Ages 0 days to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Severe Infection and Non-injury Death
- How many people
- 2,083 participants
- Where
- 2 sitesBangladesh
- Study dates
- 12 Feb 2020to 22 Oct 2022
- 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 0 days to 49 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: Healthy Bangladeshi newborns, delivered at two public hospitals (Maternal and Child Health Training Institute and Mohammadpur Fertility Services and Training Centre), and their mothers in Dhaka, Bangladesh. Newborns will be enrolled between 0 and 4 days postnatal age (n=3,000).
Core Inclusion Criteria:
- Infants up to and including 4 days of age
- Infants delivered at a study hospital
- Orally feeding currently
- Informed consent by parent or guardian
- Intends to maintain residence within the defined catchment areas (upon discharge from hospital) until 60 days of age
Core Exclusion Criteria:
- Birth weight <1500g
- Death or major surgery considered to be highly probable within first week of life
- Major congenital anomaly of the gastrointestinal tract
- Maternal HIV infection and/or history of mother ever receiving anti-retroviral drug(s) for presumed HIV infection
- Current mechanical ventilation and/or cardiac support (e.g., inotropes) and/or administration/prescription of parenteral antibiotics
- Any prenatal or postpartum use of non-dietary probiotic supplement by mother (during current pregnancy)
- Any postnatal administration of non-dietary probiotic or prebiotic supplements to infant
- Enrolment of infant in any other clinical trial involving the administration of probiotics and/or prebiotics
- Resides in the same household as another infant previously enrolled in the study, or any study within the research platform, who is currently <60 days of age; however, twins may all be enrolled simultaneously
- Multiple gestation for which the number of liveborn infants from the same pregnancy exceeds two (i.e., triplets or higher order multiples)
Trial locations and contacts
2 sites in 1 country.
Bangladesh2 sites
Maternal Child Health Training Institute
Dhaka
Mohammadpur Fertility Services Training Centre
Dhaka
About this study
Official title: Severe Infections and the Intestinal Microbiome in Young Infants in Dhaka, Bangladesh: an Observational Cohort Study
Globally, infectious diseases such as sepsis, meningitis and pneumonia are among the leading causes of neonatal deaths. A recent observational study in South Asia highlighted the contribution of both bacterial and viral infections to the burden of illness in infants <60 days of age; however, there remains a need to quantify the risk of severe infection (SI) among newborns in a Bangladeshi population. In collaboration with researchers in Bangladesh, investigators aim to generate knowledge regarding the incidence and risk factors of SI, including the composition of the intestinal microbiome, in young infants (birth to 60 days of age) in Dhaka, Bangladesh. Data will support the design and implementation of future trials to test the efficacy of novel interventions for the prevention of SI in young infants, to promote optimal growth and development, and to determine effects on other health outcomes in early infancy.
Read the detailed description
Globally, infectious diseases including sepsis, meningitis, and pneumonia are among the leading causes of neonatal deaths. In 2017, these three conditions were estimated to account for 540,000 newborn deaths worldwide, approximately 21% of all neonatal deaths globally. Previous studies have suggested that South Asia has a relatively high incidence of possible serious bacterial infection (pSBI) in young infants, particularly in areas where neonatal and under-five mortality rates are highest.
A large body of evidence from inpatient neonatal populations, and the recent evidence from the Panigrahi et al. community trial in India, support an important role of intestinal dysbiosis in the pathogenesis of sepsis/SI in young infants. This mechanism may be particularly important in low- and middle-income countries in Africa and South Asia, where low-cost routine interventions to reduce the burden of SI (e.g., probiotics or synbiotics) could have an important impact on the burden of morbidity and mortality in young infants. However, there are limited data regarding the composition of the early postnatal microbiome in the general population of infants (rather than selected groups of preterm or hospitalized newborns) in South Asia and the role of the microbiome in modulating the risk of SI.
This observational study will generate new knowledge about the incidence and risk factors of SI, including the composition of the intestinal microbiome, in young infants (birth to 60 days of age) in Dhaka, Bangladesh. The aims of this study are to:
- Estimate the incidence of SI in a facility-recruited cohort of Bangladeshi newborns during the first 60 days of life, and examine the sensitivity of the estimates to variations in SI case definitions;
- Explore the associations between maternal-infant characteristics (e.g., mode of delivery, feeding practices, gestational age, antibiotic exposure) and the risk of SI in the first 60 days of life;
- Estimate the absolute and relative stool abundances and age at initial colonization of Bifidobacterium longum subspecies (ssp.) infantis (B. infantis), Bifidobacterium longum ssp. longum (B. longum longum), Bifidobacterium breve (B. breve) and all bifidobacteria species combined during the first 60 days of life in Bangladeshi newborns, overall and within sub-groups defined by: mode of delivery, feeding practices, prior or current infant exposure to antibiotics, and whether there is colonization with the specific bacterial species or subspecies;
- Explore the associations between maternal-infant characteristics (e.g., mode of delivery, feeding practices, gestational age, antibiotic use) and stool abundance (or age at initial colonization) of B. infantis, B. longum longum, and B. breve;
- Estimate the association between stool abundance of B. infantis and SI in Bangladeshi newborns during the first 60 days of life;
- Describe the composition, diversity, and stability of the microbiome in Bangladeshi newborns at multiple time-points during the first 60-days of life, and examine how the composition, diversity, and stability varies by mode of delivery and other maternal-infant and household characteristics;
- In a facility-recruited cohort of Bangladeshi newborns, estimate the incidence proportions and/or incidence rates and/or prevalence of the following clinical outcomes up to 7 days, 28 days, 60 days of life, 3 months, and 6 months of age:
- Hospitalization for any reason other than for routine postnatal care
- Upper respiratory tract infections (URTI);
- Lower respiratory tract infections (LRTI);
- Acute or persistent diarrhea;
- Significant neurological impairment or disability diagnosed by 6 months of age; and,
- All-cause and non-injury-related mortality
- Describe child anthropometry (length, weight, and head circumference) and standardized anthropometric indices (length-for-age, weight-for age, and weight-for-height, and head circumference-for-age z-scores) up to 60 days of age in a facility-recruited cohort of Bangladeshi newborns;
- Estimate the cohort accrual rates of eligible newborns at two public maternal-child health care facilities in Dhaka, Bangladesh
Study personnel will conduct active and passive clinical surveillance and routine specimen collection (e.g. stool, nasal, skin and oral swabs etc.). Additional specimen collection may also be triggered in the event of physician-confirmed clinical severe infection, or if infants meet the case definition of LRTI (fast breathing with at least one of the following: cough, nasal congestion, or runny nose) or are hospitalized with diarrhea and/or vomiting.
- Conditions
- Severe Infection and Non-injury Death
- Keywords
- Severe infection, Sepsis, Microbiome, Bangladesh, Young infants
- Medical subject headings
- Infections, Sepsis
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of severe infection (SI) and/or non-injury death
Severe infection is defined as at least one sign of clinical severe infection (CSI) (i.e., poor feeding, lethargy, convulsions, severe chest in-drawing, fever, or hypothermia) documented by a physician and/or physician diagnosis of sepsis or another serious bacterial infection (SBI); and at least one of the following two criteria: 1) physician decision to admit to hospital, administration of at least one dose of a parenteral antibiotic on the day when CSI/sepsis/SBI is first ascertained, and treatment (or physician intention to treat) with parenteral antibiotics for at least 5 days or 2) blood and/or cerebrospinal fluid (CSF) culture positive for a pathogenic bacterial or fungal organism.
Non-injury death refers to death due to any cause except death that was directly caused by physical trauma (medically certified cause of death and/or verbal autopsy).
Measured: Up to 60 days of age
Absolute abundance of Bifidobacterium infantis, Bifidobacterium longum longum and Bifidobacterium breve in stool
Absolute abundance (AA) of specific bacteria in stool will be expressed as the log number of cells of a particular bacterial species or subspecies per gram (g) of stool, as detected by quantitative polymerase chair reaction (qPCR). If a direct cell count is unfeasible, AA will be expressed as log colony forming units of a particular bacterial species or subspecies per gram of stool.
Measured: Up to 60 days of age
Relative abundance of Bifidobacterium infantis, Bifidobacterium longum longum and Bifidobacterium breve in stool
Relative abundance (RA) will be expressed as the number of gene copies from a particular genus/species/sub-species of interest proportional to the total number of 16S rRNA gene copies per gram (g) of stool. For total bifidobacteria, only RA will be expressed.
Measured: Up to 60 days of age
Infant age at initial colonization with bacterial strains
Age at initial colonization can only be defined at the level of the infant and will refer to each infant's first age (in days) at which colonization was detected or predicted to have occurred. This age may be derived empirically or using longitudinal modeling of infant-specific abundance trajectories. Colonization is a dichotomous variable that will be defined as an absolute abundance of a particular organism that exceeds a specified threshold. The term colonization refers here to the empirical detection of bacterial DNA at or above a particular level of abundance in stool, and will be used as a surrogate of intestinal colonization (in the absence of direct measurement of specific sites within the intestine).
Measured: Up to 60 days of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2019
- Study start12 Feb 2020
- Primary completion22 Oct 2022
- Study completion22 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe Infection and Non-injury DeathStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe 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
- 2,083 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh, Child Health Research Foundation, Bangladesh, Boston University, McGill University, University of California, San Diego
- Responsible party
- Principal investigator, Daniel Roth, The Hospital for Sick Children
- Investigators
- Daniel Roth, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04012190
- Sponsor's protocol ID
- 1000063899
- Status last verified
- Oct 2022
- First submitted
- 19 Jun 2019
- Last updated
- 31 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Severe Infections and the Intestinal Microbiome in Young Infants in Dhaka, Bangladesh: an Observational Cohort Study
- ClinicalTrials.gov ID
- NCT04012190
- Acronym / sponsor ID
- 1000063899
- Conditions
- Severe Infection and Non-injury Death
- Keywords
- Severe infection, Sepsis, Microbiome, Bangladesh, Young infants
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,083 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh, Child Health Research Foundation, Bangladesh, Boston University, McGill University, University of California, San Diego
- Study start
- 12 Feb 2020 (actual)
- Primary completion
- 22 Oct 2022 (actual)
- Study completion
- 22 Oct 2022 (actual)
- First posted
- 9 Jul 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.
Globally, infectious diseases such as sepsis, meningitis and pneumonia are among the leading causes of neonatal deaths. A recent observational study in South Asia highlighted the contribution of both bacterial and viral infections to the burden of illness in infants <60 days of age; however, there remains a need to quantify the risk of severe infection (SI) among newborns in a Bangladeshi population. In collaboration with researchers in Bangladesh, investigators aim to generate knowledge regarding the incidence and risk factors of SI, including the composition of the intestinal microbiome, in young infants (birth to 60 days of age) in Dhaka, Bangladesh. Data will support the design and implementation of future trials to test the efficacy of novel interventions for the prevention of SI in young infants, to promote optimal growth and development, and to determine effects on other health outcomes in early infancy.
Detailed description
Globally, infectious diseases including sepsis, meningitis, and pneumonia are among the leading causes of neonatal deaths. In 2017, these three conditions were estimated to account for 540,000 newborn deaths worldwide, approximately 21% of all neonatal deaths globally. Previous studies have suggested that South Asia has a relatively high incidence of possible serious bacterial infection (pSBI) in young infants, particularly in areas where neonatal and under-five mortality rates are highest.
A large body of evidence from inpatient neonatal populations, and the recent evidence from the Panigrahi et al. community trial in India, support an important role of intestinal dysbiosis in the pathogenesis of sepsis/SI in young infants. This mechanism may be particularly important in low- and middle-income countries in Africa and South Asia, where low-cost routine interventions to reduce the burden of SI (e.g., probiotics or synbiotics) could have an important impact on the burden of morbidity and mortality in young infants. However, there are limited data regarding the composition of the early postnatal microbiome in the general population of infants (rather than selected groups of preterm or hospitalized newborns) in South Asia and the role of the microbiome in modulating the risk of SI.
This observational study will generate new knowledge about the incidence and risk factors of SI, including the composition of the intestinal microbiome, in young infants (birth to 60 days of age) in Dhaka, Bangladesh. The aims of this study are to:
- Estimate the incidence of SI in a facility-recruited cohort of Bangladeshi newborns during the first 60 days of life, and examine the sensitivity of the estimates to variations in SI case definitions;
- Explore the associations between maternal-infant characteristics (e.g., mode of delivery, feeding practices, gestational age, antibiotic exposure) and the risk of SI in the first 60 days of life;
- Estimate the absolute and relative stool abundances and age at initial colonization of Bifidobacterium longum subspecies (ssp.) infantis (B. infantis), Bifidobacterium longum ssp. longum (B. longum longum), Bifidobacterium breve (B. breve) and all bifidobacteria species combined during the first 60 days of life in Bangladeshi newborns, overall and within sub-groups defined by: mode of delivery, feeding practices, prior or current infant exposure to antibiotics, and whether there is colonization with the specific bacterial species or subspecies;
- Explore the associations between maternal-infant characteristics (e.g., mode of delivery, feeding practices, gestational age, antibiotic use) and stool abundance (or age at initial colonization) of B. infantis, B. longum longum, and B. breve;
- Estimate the association between stool abundance of B. infantis and SI in Bangladeshi newborns during the first 60 days of life;
- Describe the composition, diversity, and stability of the microbiome in Bangladeshi newborns at multiple time-points during the first 60-days of life, and examine how the composition, diversity, and stability varies by mode of delivery and other maternal-infant and household characteristics;
- In a facility-recruited cohort of Bangladeshi newborns, estimate the incidence proportions and/or incidence rates and/or prevalence of the following clinical outcomes up to 7 days, 28 days, 60 days of life, 3 months, and 6 months of age:
- Hospitalization for any reason other than for routine postnatal care
- Upper respiratory tract infections (URTI);
- Lower respiratory tract infections (LRTI);
- Acute or persistent diarrhea;
- Significant neurological impairment or disability diagnosed by 6 months of age; and,
- All-cause and non-injury-related mortality
- Describe child anthropometry (length, weight, and head circumference) and standardized anthropometric indices (length-for-age, weight-for age, and weight-for-height, and head circumference-for-age z-scores) up to 60 days of age in a facility-recruited cohort of Bangladeshi newborns;
- Estimate the cohort accrual rates of eligible newborns at two public maternal-child health care facilities in Dhaka, Bangladesh
Study personnel will conduct active and passive clinical surveillance and routine specimen collection (e.g. stool, nasal, skin and oral swabs etc.). Additional specimen collection may also be triggered in the event of physician-confirmed clinical severe infection, or if infants meet the case definition of LRTI (fast breathing with at least one of the following: cough, nasal congestion, or runny nose) or are hospitalized with diarrhea and/or vomiting.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 0 days to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Healthy Bangladeshi newborns, delivered at two public hospitals (Maternal and Child Health Training Institute and Mohammadpur Fertility Services and Training Centre), and their mothers in Dhaka, Bangladesh. Newborns will be enrolled between 0 and 4 days postnatal age (n=3,000).
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
Incidence of severe infection (SI) and/or non-injury death
Time frame: Up to 60 days of age
Severe infection is defined as at least one sign of clinical severe infection (CSI) (i.e., poor feeding, lethargy, convulsions, severe chest in-drawing, fever, or hypothermia) documented by a physician and/or physician diagnosis of sepsis or another serious bacterial infection (SBI); and at least one of the following two criteria: 1) physician decision to admit to hospital, administration of at least one dose of a parenteral antibiotic on the day when CSI/sepsis/SBI is first ascertained, and treatment (or physician intention to treat) with parenteral antibiotics for at least 5 days or 2) blood and/or cerebrospinal fluid (CSF) culture positive for a pathogenic bacterial or fungal organism. Non-injury death refers to death due to any cause except death that was directly caused by physical trauma (medically certified cause of death and/or verbal autopsy).
Absolute abundance of Bifidobacterium infantis, Bifidobacterium longum longum and Bifidobacterium breve in stool
Time frame: Up to 60 days of age
Absolute abundance (AA) of specific bacteria in stool will be expressed as the log number of cells of a particular bacterial species or subspecies per gram (g) of stool, as detected by quantitative polymerase chair reaction (qPCR). If a direct cell count is unfeasible, AA will be expressed as log colony forming units of a particular bacterial species or subspecies per gram of stool.
Relative abundance of Bifidobacterium infantis, Bifidobacterium longum longum and Bifidobacterium breve in stool
Time frame: Up to 60 days of age
Relative abundance (RA) will be expressed as the number of gene copies from a particular genus/species/sub-species of interest proportional to the total number of 16S rRNA gene copies per gram (g) of stool. For total bifidobacteria, only RA will be expressed.
Infant age at initial colonization with bacterial strains
Time frame: Up to 60 days of age
Age at initial colonization can only be defined at the level of the infant and will refer to each infant's first age (in days) at which colonization was detected or predicted to have occurred. This age may be derived empirically or using longitudinal modeling of infant-specific abundance trajectories. Colonization is a dichotomous variable that will be defined as an absolute abundance of a particular organism that exceeds a specified threshold. The term colonization refers here to the empirical detection of bacterial DNA at or above a particular level of abundance in stool, and will be used as a surrogate of intestinal colonization (in the absence of direct measurement of specific sites within the intestine).
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 Oct 2022.
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.
Daniel Roth principal investigator
The Hospital for Sick Children
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Severe Infection and Non-injury Death, run by The Hospital for Sick Children at 2 sites in Bangladesh.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Bangladesh. 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?
Incidence of severe infection (SI) and/or non-injury death (time frame: Up to 60 days of age). The study lists 4 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 Oct 2022.