Childhood Acute Illness and Nutrition Network

NCT ID: NCT03208725

Last Updated: 2020-05-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Total Enrollment

4335 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-11-30

Study Completion Date

2020-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The CHAIN Network aims to identify modifiable biomedical and social factors driving the greatly increased risk of mortality among young undernourished children admitted to hospital with acute illness, as inpatients and after discharge. The study will inform priorities, risks and targeting for multi-faceted interventional trials.

CHAIN is a multi-centre cohort study with a nested case control analysis of stored biological samples. Study sites are located in Africa and South Asia. Children will be recruited at admission to hospital, stratified by nutritional status. Exposures will be assessed at admission, during hospitalisation, at discharge, and at two time points after discharge. The main outcomes of interest are mortality, re-admission to hospital and failure of nutritional recovery up to 180 days after discharge. To determine community health norms, an additional sample of children living in the same communities will be enrolled and assessed at one time point only.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Despite an overall reduction of child mortality in LMICs, acutely-ill undernourished children continue to have a greatly elevated risk of death, both during hospitalisation and following discharge. However, we currently lack robust evidence for their management. Factors underlying the risks of mortality may relate to the acute illness itself, to children's longer term health trajectories, or to the home nutritional and care environment. The ultimate goal of the CHAIN Network is to identify and prioritize actionable intervention targets to reduce mortality among acutely ill undernourished children.

CHAIN's initial aim is to better understand the characteristics that determine increased risk of mortality in this vulnerable population, whether biological (related to infection, immunity and metabolism), nutritional (intake and anthropometry), health system factors (affecting management and discharge) or behavioural (community/caregiver interactions). CHAIN brings clinicians and scientists together from a variety of high-burden settings in Africa and South Asia. CHAIN will establish prospective cohorts of acutely ill young children across different geographies with differing population, social and environmental characteristics (stunted vs. wasting, rural vs. urban and presence of risk factors such as malaria and HIV).

Eight sites will be involved, including three hospitals in Kenya (Kilifi County, Migori County and Mbagathi District), two in Bangladesh (Matlab and the icddr,b Dhaka), and one in each of Uganda (Mulago), Malawi (Queen Elizabeth Community Hospital), Pakistan (Civil Hospital Karachi) and in West Africa (TBA). Site will enroll children at admission to hospital, and assess their clinical, social and economic status at admission, during hospitalisation, at discharge and during follow up for 180 days after discharge. The sites will also enrol children from the community to determine community norms (where ill and undernourished children would be expected to typically recover to). Protocols and procedures will be carefully harmonised across sites.

Children aged 2 months to 2 years admitted to hospital will be considered for inclusion and enrolment stratified by nutritional status. Following informed consent, baseline data of prognostic importance, including demographic and social information, a detailed clinical examination, anthropometry and measurement of vital signs, including pulse oximetry, will be collected using a standard proforma. A research blood sample will be collected together with the routine clinical blood draw to minimize the patient's discomfort. Rectal swabs and faecal sample will also be obtained from all children.

During admission, care will be provided according to WHO and national guidelines. Children will be reviewed daily and clinical features, progress and treatment received recorded on a structured case report form. In the event of death in hospital, a standard audit questionnaire will be completed. During admission, primary caregivers, usually the mother, will be interviewed screened for mental health problems. At discharge, anthropometry, a clinical assessment and blood, rectal swab and whole stool collected. Families will be linked with chronic care services where needed.

A home visit will be conducted for all participants, the GPS location recorded. Information homestead infrastructure, water and sanitation, population, livelihood, child care and socioeconomic characteristics. Children will be followed up at 45, 90 and 180 days after discharge. A health questionnaire will document health and social events, and dietary intake. Anthropometry, and faecal and blood samples collected.

Caregivers will be asked to attend the study hospital should the caregiver believes they may require hospitalisation. Study participants who are re-admitted to hospital will undergo standardised clinical assessment including history, examination and sample collection. In the event of death occurring outside the study hospital, a standard verbal autopsy (VA) will be completed by trained staff within 28 days of becoming aware of a death. VAs along with all available information will be used to ascribe causes of death.

Community participants will be invited to the study clinic for assessment. Following informed consent, they will have a clinical examination, anthropometry, blood and stool samples as children who are admitted. Children requiring non-urgent medical care will be eligible for inclusion as community participants but will be given basic treatment in the study clinic and/or referred to appropriate treatment centres. Study staff will refer community participants with incomplete vaccination or requiring care for chronic conditions as needed.

Several domains of exposure will be assessed: demographic, nutrition and metabolism; acute and chronic conditions; community-acquired and nosocomial infections (including antimicrobial resistance); gut function \& dysbiosis; inflammation; responses to treatment; and the home care environment.

Successful design of an intervention package to address post-discharge child mortality will require attention social and economic agency and vulnerability, access and interactions with health services, and ethical considerations. A qualitative sub-study will examine these factors in context in rural and urban sites in Kenya and Bangladesh to identify critical social limitations and potential approaches to intervention. These data will inform the network's development, piloting, and implementation of interventions.

Additional sub-studies at a subset of sites will also examine in more detail the diagnosis and role of TB; and changes in functional immune responses; body composition and neurodevelopment during follow up.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Malnutrition Pneumonia Diarrhea Sepsis Bacteremia HIV/AIDS TB Enteropathy Antibiotic Resistant Strain

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Hospitalized children with severe wasting or kwashiorkor (SWK)

Children recruited at admission to hospital and followed up for 180 days post-discharge.

No interventions assigned to this group

Community reference participants (CP)

Children recruited from the community who are seen a single appointment in the community.

No interventions assigned to this group

Hospitalized children with moderate wasting (MW)

Children recruited at admission to hospital and followed up for 180 days post-discharge.

No interventions assigned to this group

Hospitalized children without wasting (NW)

Children recruited at admission to hospital and followed up for 180 days post-discharge.

No interventions assigned to this group

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Children 2 months-23 months.
* Admitted to hospital.
* Planning to remain within the hospital catchment area and willing to come for specified visits during the 6 month follow up period.
* Parent or guardian consents on child's behalf.


* Aged 2 to 23 months
* Living in the same community as the acutely ill children recruited.
* Not having an acute illness requiring hospital admission
* Absence of known, but untreated HIV or TB
* Not admitted to hospital within the last 14 days
* Not previously included in the study
* Parent or guardian consents on child's behalf.

Exclusion Criteria

* Requiring immediate resuscitation at admission to hospital\*
* Unable to tolerate oral feeds while in his/her usual state of health
* Underlying terminal illness that in the opinion of the treating physician is likely to lead to death within 6 months (e.g., cancer, congenital heart disease)
* Diagnosed with a condition that in the opinion of the treating physician is likely to require surgery within 6 months
* Diagnosed chromosomal abnormality (syndromically or genetically diagnosed abnormality)
* Primary reason for admission is poisoning, trauma or a surgical condition
* Previously enrolled in this study
* Sibling currently or previously enrolled in this study

(\* children requiring resuscitation will be defined as those with on-going cardiac or pulmonary arrest or judged to be peri-arrest by the attending physician)
Minimum Eligible Age

2 Months

Maximum Eligible Age

23 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Washington

OTHER

Sponsor Role collaborator

Kenya Medical Research Institute

OTHER

Sponsor Role collaborator

KEMRI-Wellcome Trust Collaborative Research Program

OTHER

Sponsor Role collaborator

Makerere University

OTHER

Sponsor Role collaborator

Oregon Health and Science University

OTHER

Sponsor Role collaborator

The Hospital for Sick Children

OTHER

Sponsor Role collaborator

University of Amsterdam

OTHER

Sponsor Role collaborator

University of Malawi

OTHER

Sponsor Role collaborator

Aga Khan University

OTHER

Sponsor Role collaborator

International Centre for Diarrhoeal Disease Research, Bangladesh

OTHER

Sponsor Role collaborator

University of Oxford

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

James A Berkley, MBBS, FRCPCH

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Judd L Wilson, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Matlab Hospital

Dhaka, Chittagong, Bangladesh

Site Status

ICDDR,B Dhaka Hospital

Dhaka, , Bangladesh

Site Status

Kilifi County Hospital

Kilifi, , Kenya

Site Status

Migori County Hospital

Migori, , Kenya

Site Status

Mbagathi District Hospital

Nairobi, , Kenya

Site Status

Queen Elizabeth Central Hospital

Blantyre, , Malawi

Site Status

Civil Hospital Karachi

Karachi, , Pakistan

Site Status

Mulago Hospital

Kampala, , Uganda

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Bangladesh Kenya Malawi Pakistan Uganda

References

Explore related publications, articles, or registry entries linked to this study.

Njunge JM, Tickell K, Diallo AH, Sayeem Bin Shahid ASM, Gazi MA, Saleem A, Kazi Z, Ali S, Tigoi C, Mupere E, Lancioni CL, Yoshioka E, Chisti MJ, Mburu M, Ngari M, Ngao N, Gichuki B, Omer E, Gumbi W, Singa B, Bandsma R, Ahmed T, Voskuijl W, Williams TN, Macharia A, Makale J, Mitchel A, Williams J, Gogain J, Janjic N, Mandal R, Wishart DS, Wu H, Xia L, Routledge M, Gong YY, Espinosa C, Aghaeepour N, Liu J, Houpt E, Lawley TD, Browne H, Shao Y, Rwigi D, Kariuki K, Kaburu T, Uhlig HH, Gartner L, Jones K, Koulman A, Walson J, Berkley J. The Childhood Acute Illness and Nutrition (CHAIN) network nested case-cohort study protocol: a multi-omics approach to understanding mortality among children in sub-Saharan Africa and South Asia. Gates Open Res. 2022 Nov 3;6:77. doi: 10.12688/gatesopenres.13635.2. eCollection 2022.

Reference Type DERIVED
PMID: 36415883 (View on PubMed)

Tickell KD, Denno DM, Saleem A, Ali A, Kazi Z, Singa BO, Otieno C, Mutinda C, Ochuodho V, Richardson BA, Asbjornsdottir KH, Hawes SE, Berkley JA, Walson JL. Enteric Permeability, Systemic Inflammation, and Post-Discharge Growth Among a Cohort of Hospitalized Children in Kenya and Pakistan. J Pediatr Gastroenterol Nutr. 2022 Dec 1;75(6):768-774. doi: 10.1097/MPG.0000000000003619. Epub 2022 Sep 20.

Reference Type DERIVED
PMID: 36123771 (View on PubMed)

Childhood Acute Illness and Nutrition Network. Childhood Acute Illness and Nutrition (CHAIN) Network: a protocol for a multi-site prospective cohort study to identify modifiable risk factors for mortality among acutely ill children in Africa and Asia. BMJ Open. 2019 May 5;9(5):e028454. doi: 10.1136/bmjopen-2018-028454.

Reference Type DERIVED
PMID: 31061058 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

https://bmjopen.bmj.com/content/9/5/e028454.long

Childhood Acute Illness and Nutrition (CHAIN) Network: a protocol for a multi-site prospective cohort study to identify modifiable risk factors for mortality among acutely ill children in Africa and Asia

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

OPP1131320

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.