Clinical trial NCT05065320: Tools for the Integrated Management of Childhood Illness: Cross-country Quasi-experimental Pre-post Study in Kenya and Senegal
Official title: Tools for the Integrated Management of Childhood Illness: Evaluation of Pulse Oximetry and Clinical Decision Support Algorithms in Primary Care. Cross-country Quasi-experimental Pre-post Study, With Embedded Mixed Methods Studies, Cost and Modelled Cost-effectiveness in Kenya and Senegal
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Childhood Severe Illness
Pneumonia
Primary Health Care
Hypoxia
Referreal and Consultation
Decision Support Systems, Clinical
Oxymetry
Lead sponsor: Swiss Tropical & Public Health Institute
Sponsor class: OTHER
Collaborators: name: PATH
name: University of Nairobi
name: Cheikh Anta Diop University, Senegal
name: Burnet Institute
First posted: 2021-10-04
Enrollment: 51590
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Children 0 - 59 months, for whom caregivers provide consent, will be eligible if attending any study facility with an illness, excluding those admitted as inpatients within the facility, or attending for a consultation related to trauma only.

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 quasi-experimental pre-post studies conducted in Kenya and Senegal. In India and Tanzania, pragmatic cluster randomised controlled trials (RCTs) are conducted (NCT04910750). 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 and key informant interviews, routine data review, and an economic evaluation.

We enrol sick children 0 to 59 months of age attending government primary care facilities in before and after implementation of pulse oximetry and CDSA. Interventions are implemented with a package of training on the use of devices and refresher IMCI, supportive supervision, operational support and community engagement.

As part of the intervention, facilities are provided with handheld, UNICEF-approved, pulse oximeters along with guidance and training for healthcare providers. In Senegal, 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 Kenya, healthcare providers are advised to measure oxygen saturation for all sick children. Providers are advised to urgently refer children with SpO2 \<90% in Kenya and \<92% in Senegal. 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. Two primary outcomes are assessed for the quasi-experimental pre-post study: referrals to a higher level of care at Day 0 consultation; and antibiotic prescriptions on Day 0. These reflect the aim that the intervention increases detection of severe disease, and therefore increasing referral, whilst promoting antimicrobial stewardship, and therefore reducing antibiotic prescription. Secondary outcomes, relating to hypoxaemia, hospitalisation, referral, antimicrobial prescription, follow-up, health status are further detailed in the attached full protocol and statistical analysis plan available.

The pre-post study sample size was originally estimated for a planned 15 month study, with 3 months pre- (Q1) and 12 months post-intervention (Q2-5), with comparison of Q1 and Q5 for the primary outcome. Calculations were based on detecting a ≥50% increase in Day 0 referrals (from 3%, based on DHIS2, SPA and facility estimates), with 80% power, 0.05 alpha and ICC of 0.00547. A relatively large detectable difference was chosen given that a relatively high proportion of referrals may not be completed.5 46 Day 0 referrals, rather than antibiotic prescriptions (with baseline estimated at 60% with ICC 0.05), drove the sample size calculation. We estimated needing 17 facilities, recruiting an average of 690 children per facility per 3-month period in Kenya, and 18 facilities recruiting 510 children per facility per period in Senegal.

Following lower than anticipated recruitment in the baseline of the pre-post study, sample size was re-evaluated resulting in a decision to add two facilities per country, extend the baseline (to 6-7 months), and reduce the post-intervention period (to 9-10 months). A minimum of 7429 and 6760 children were estimated to be needed in each period in Kenya and Senegal respectively, with recruitment continuing after meeting the minimum sample size in order to allow for description of changes over time and with overlapping seasonal periods, in line with the intention of the original design.

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: Inclusion Criteria:

* Children 0-59 months of age 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)

Exclusion Criteria:

* 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 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 prescribed an antibiotic at Day 0
timeFrame: At time of enrolment
Secondary 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
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 cured (defined as caregiver reported recovery from illness) by Day 7
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 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: Nairobi
country: Kenya
facility: University of Nairobi
city: Dakar
country: Senegal
facility: UCAD
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: