Clinical trial NCT04910750: Tools for the Integrated Management of Childhood Illness (TIMCI): Evaluation of Pulse Oximetry & Clinical Decision Support Algorithms in Primary Care
Official title: Tools for the Integrated Management of Childhood Illness: Evaluation of Pulse Oximetry & Clinical Decision Support Algorithms in Primary Care - Pragmatic Cluster Randomised Controlled Trial, With Embedded Mixed Methods, Cost & Cost-effectiveness Studies in India and Tanzania
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pneumonia
Primary Health Care
Child Health
Hypoxia
Referral and Consultation
Decision Support Systems, Clinical
Oxymetry
Lead sponsor: Swiss Tropical & Public Health Institute
Sponsor class: OTHER
Collaborators: name: Ifakara Health Institute
name: King George's Medical University
name: University of Waterloo
name: PATH
First posted: 2021-06-02
Enrollment: 167517
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: By introducing pulse oximetry, with or without clinical decision support algorithms, to primary care facilities in India, Kenya, Senegal and Tanzania, the Tools for Integrated Management of Childhood Illness (TIMCI) project aims to contribute to reducing morbidity and mortality for sick children under-five while supporting the rational and efficient use of diagnostics and medicines by healthcare providers.

The multi-country, multi-method evaluation aims to generate evidence on the health and quality of care impact, operational priorities, cost and cost-effectiveness of introducing these tools to facilitate national and international decision-making on scale-up.

Detailed description: This registry entry describes the pragmatic cluster randomised controlled trials (RCTs) conducted in India and Tanzania. In Kenya and Senegal, quasi-experimental pre-post studies are conducted (NCT05065320). These studies evaluating health, clinical and quality of care impact are complemented by embedded multi-method studies in all countries, including modified Service Provision Assessments, facility-based process mapping and time-flow studies, in-depth interviews (IDIs) with caregivers and healthcare providers, online key stakeholder surveys, routine data review, and an economic evaluation.

We enrol sick children 0 to 59 months of age attending government primary care facilities a pragmatic parallel group, superiority cluster randomised controlled trial (RCT). Primary care facilities randomly are allocated (1:1) in India to pulse oximetry or control, and (1:1:1) in Tanzania to pulse oximetry plus CDSA, pulse oximetry, or control. Interventions are implemented with a package of training on the use of devices and refresher IMCI, supportive supervision, operational support and community engagement. IMCI refresher training is provided to all arms.

Providers at intervention facilities are provided with handheld, UNICEF-approved, pulse oximeters along with guidance and training in line with government-approved criteria. In Tanzania, healthcare providers are advised to measure oxygen saturation (SpO2) on all children under 2 months of age, all children 2 to 59 months of age with cough or difficulty breathing or with signs of moderate or severe disease based on Integrated Management of Childhood Illness (IMCI); in India, healthcare providers are advised to measure oxygen saturation for all sick children. Providers are advised to urgently refer children with SpO2 \<90%. The tablet-based CDSA provides step-by-step support to healthcare providers through consultations, providing national guideline-based recommendations on assessment, diagnosis and treatment based tailored to the individual child based on information entered by the provider. Following training, providers are advised to use CDSA for all consultations with sick children under 5 years of age.

Sociodemographic and clinical data are collected from caregivers and records of enrolled sick children at study facilities, with phone follow-up on Day 7 and Day 28. Two primary outcomes are assessed for the RCT: severe complications by Day 7 (mortality and 'secondary hospitalisations' i.e. delayed ≥24 hours from the Day 0 consultation, or without referral); and 'primary' hospitalisations (within 24hrs the Day 0 consultation and with referral). Secondary outcomes for the RCT, relating to hypoxaemia, referral, antimicrobial prescription, follow-up, health status, are further detailed in the attached full protocol and statistical analysis plan available.

The RCT sample size was estimated based on planned enrolment over 12 months and ability to detect a ≥30% decrease in severe complications (from 1.1%22) and ≥30% increase in primary hospitalisations (from 1.5%, based on facility estimates) for each arm compared to control with 80% power, 0.05 alpha per arm, and intra-cluster correlation coefficient (ICC) of 0.00147. Anticipated feasible enrolment rates were based on DHIS2 and facility data. In Tanzania, 22 clusters per arm, each recruiting an average of 1680 children, were estimated to be needed (total 110,880). In India, 40 clusters per arm, each recruiting an average of 510 children, were estimated to be needed (total 40,800).

Study approval has been granted by all relevant institutional review boards, national and WHO ethical review committees. Findings will be shared with communities, healthcare providers, Ministries of Health and other local, national and international stakeholders to facilitate evidence-based decision-making on scale-up.

Eligibility criteria: Individual child inclusion:

* Children 0 - 59 months for whom caregivers provide consent
* Consulting for an illness, or reported to be unwell when attending for a routine visit (e.g. vaccination, growth or chronic disease monitoring)

Individual child exclusion:

* Children in the immediate post-natal period or first day of life
* Attending for a consultation related to trauma only (including new and follow-up presentations for burns, injuries, wounds)
* Admitted within an inpatient part of the facility (including neonates delivered at the facility admitted with their mother)
* Enrolled in the study within the preceding 28 days at any study facility

Primary outcomes:
measure: Proportion of children with a severe complication (death or secondary hospitalisation) by Day 7
timeFrame: From enrolment up to 7 days after
measure: Proportion of children admitted to hospital within 24 hours of the Day 0 primary care consultation and as a result of a referral
timeFrame: From enrolment up to 1 day after
Secondary outcomes:
measure: Proportion of children with severe complication (death or secondary hospitalisation) by Day 28
timeFrame: From enrolment up to 28 days after
measure: Proportion of children cured (defined as caregiver reported recovery from illness) by Day 7
timeFrame: From enrolment up to 10 days after
measure: Proportion of children referred by a primary care healthcare provider to a higher level of care (either to a hospital or to an inpatient part of a larger primary healthcare facility) at Day 0 consultation
timeFrame: At time of enrolment
measure: Proportion of children who completed referral, as reported at day 7 follow-up
timeFrame: From enrolment up to 10 days after
measure: Proportion of children with non-severe disease referred to a higher level of care on Day 0
timeFrame: At time of enrolment
measure: Average length of stay (in days) of children admitted to hospital
timeFrame: From hospital admission to discharge
measure: Proportion of children prescribed an antibiotic at Day 0
timeFrame: At time of enrolment
measure: Proportion of children prescribed a diagnosis-appropriate antibiotic
timeFrame: At time of enrolment
measure: Proportion of febrile children tested for malaria at Day 0
timeFrame: At time of enrolment
measure: Proportion of malaria positive children prescribed an antimalarial
timeFrame: At time of enrolment
measure: Proportion of malaria negative children prescribed an antimalarial
timeFrame: At time of enrolment
measure: Proportion of untested children prescribed an antimalarial
timeFrame: At time of enrolment
measure: Proportion of children with severe, moderate and mild hypoxaemia, adjusted for sites at high altitude
timeFrame: At time of enrolment
measure: Proportion of children with hypoxaemia (according to differing cut-offs) with severe complication
timeFrame: At time of enrolment
measure: Proportion of children with severe hypoxaemia not meeting any other clinical criteria for severe disease
timeFrame: At time of enrolment
measure: Proportion of children referred with hypoxaemia who receive oxygen at hospital
timeFrame: At time of enrolment and at time of hospitalization
measure: Proportion of children attending scheduled follow-up at the same facility by Day 7
timeFrame: From enrolment up to 7 days after
measure: Proportion of children presenting for unscheduled follow-up to any health facility by Day 7
timeFrame: From enrolment up to 7 days after
Other outcomes:
Locations:
city: Kaliua
country: Tanzania
facility: Bukemba
city: Kaliua
country: Tanzania
facility: Igombe 60
city: Kaliua
country: Tanzania
facility: Imalamihayo
city: Kaliua
country: Tanzania
facility: Kazaroho
city: Kaliua
country: Tanzania
facility: Seleli
city: Kaliua
country: Tanzania
facility: Ulyankulu
city: Kaliua
country: Tanzania
facility: Uyowa
city: Sengerema
country: Tanzania
facility: Igalagalilo
city: Sengerema
country: Tanzania
facility: Kagunga
city: Sengerema
country: Tanzania
facility: Kamanga
city: Sengerema
country: Tanzania
facility: Kasungamile
city: Sengerema
country: Tanzania
facility: Mulaga
city: Sengerema
country: Tanzania
facility: Mwabaluhi
city: Sengerema
country: Tanzania
facility: Nyamazugo
city: Sengerema
country: Tanzania
facility: Sengerema Secondary
city: Sengerema
country: Tanzania
facility: Sengerema
city: Tanga
country: Tanzania
facility: Duga
city: Tanga
country: Tanzania
facility: Kange
city: Tanga
country: Tanzania
facility: Kisosora
city: Tanga
country: Tanzania
facility: Kwanjekanyota
city: Tanga
country: Tanzania
facility: Machui
city: Tanga
country: Tanzania
facility: Mafuriko
city: Tanga
country: Tanzania
facility: Magaoni
city: Tanga
country: Tanzania
facility: Mpirani
city: Tanga
country: Tanzania
facility: Mwakidila
city: Tanga
country: Tanzania
facility: Ngamiani
city: Tanga
country: Tanzania
facility: Nguvumali
Study officials:
affiliation: Swiss Tropical & Public Health Institute
name: Kaspar Wyss, Prof, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Swiss Tropical & Public Health Institute
name: Valérie D'Acremont, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: