SEPSIS Observational Cohort Study in Young Infants in Bangladesh

NCT04012190 | Completed DMC

• 1 other identifier: 1000063899
• Study Type: observational
• Target: 2,083
• Locations: 1 country
• Sites: 2

Brief 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 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.

Conditions

Severe Infection and Non-injury Death

Keywords

Severe infection; Sepsis; Microbiome; Bangladesh; Young infants

Outcome Measures

Primary Outcomes (4)

• 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).

  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.

  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.

  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).

  Up to 60 days of age

Eligibility Criteria

• Age: 0 Days - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

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).

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator
• Child Health Research Foundation, Bangladesh: collaborator
• Boston University: collaborator
• McGill University: collaborator
• University of California, San Diego: collaborator

Study Sites (2)

Maternal Child Health Training Institute

Dhaka, Bangladesh

Location

Mohammadpur Fertility Services Training Centre

Dhaka, Bangladesh

Location

Biospecimen

Retention: SAMPLES WITH DNA

Routine specimen collection: 1. Infant: stool; nasal, skin, oral swabs; blood. Skin swabs, oral swabs and blood will only be collected in a sub-set of participants. 2. Maternal: stool, vaginal swabs, breast milk. Stool and vaginal swabs will only be collected in a sub-set of mothers. 3. Stool sample from a sibling closest in age to the participant will be collected from a subset of participants (excluding twin). Specimen collection triggered by presence of clinical severe infection (CSI): infant stool, nasal swab, blood, urine; and, skin swabs and cerebrospinal fluid (CSF) at treating physician's discretion. Nasal swabs will also be collected from infants with LRTI (fast breathing with at least one of cough, nasal congestion, or runny nose) or in hospitalized infants with diarrhea and/or vomiting.

MeSH Terms

Conditions

Infections; Sepsis

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Daniel Roth

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientist

Study Record Dates

• First Submitted: June 19, 2019
• First Posted: July 9, 2019
• Study Start: February 12, 2020
• Primary Completion: October 22, 2022
• Study Completion: October 22, 2022
• Last Updated: October 31, 2022

Record last verified: 2022-10

Locations

BA (2)