Clinical trial NCT05914324: Outpatient Pediatric Pulse Oximeters in Africa
Official title: Evaluating Novel Pediatric Pulse Oximeters for Outpatient Child Pneumonia Care in Sub-Saharan Africa
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Child
Infant
Respiratory Tract Infections
Hypoxia
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: University of Stellenbosch
name: Karolinska Institutet
name: Baylor College of Medicine
name: Fogarty International Center of the National Institute of Health
name: Thrasher Research Fund
First posted: 2023-06-22
Enrollment: 1200
Sex: ALL
Minimum age (years): 0
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pragmatic 3-arm cluster randomised controlled trial (cRCT), conducted over a 18-month period. Clusters are defined as outpatient facilities (PHC, CDC, CHC), and the primary and secondary child-level outcomes will be assessed through a prospective cohort study. An embedded mixed-methods concurrent process evaluation will be conducted.
Primary purpose: TREATMENT

Brief summary: The primary objective of this clinical trial is to evaluate the performance of three pulse oximeters during outpatient care within Cape Town, South Africa. This objective will be achieved through generating evidence on how, why, for whom, to what extent and at what cost can paediatric pulse oximetry devices improve the management of hypoxemic children. This will be done with two inter-linked studies:

* Aim 1: Determine the impact of two novel paediatric pulse oximeter devices on the correct management of hypoxaemia.
* Aim 2: Describe the burden of hypoxaemia and risks for mortality amongst children presenting with acute respiratory infections in a low-resource setting in Cape Town.

Detailed description: Background:

Lower respiratory tract infections (LRI) remain the leading infectious cause of death globally for children younger than five years.1 Alarmingly, \>50% of LRI deaths occurred in low and middle-income countries (LMICs) in sub-Saharan Africa, with inequitable distribution both between and within countries.2 Key quality-of-care implementation gaps have hampered the effectiveness of the World Health Organization (WHO) Integrated Management of Childhood Illnesses (IMCI) guidelines used for pediatric LRI care in LMICs.3 Evaluations of Integrated Management of Childhood Illness (IMCI) guidelines have identified inadequate triaging and therefore results in a failure to identify children at higher risk of death. Interventions to improve the sensitivity and specificity of the IMCI approach in identifying severely ill children could improve outcomes. Routine use of pulse oximetry, to non-invasively measure peripheral oxyhemoglobin saturation (SpO2), is poorly implemented at the primary healthcare (PHC) levels in LMICs, and therefore provides one such opportunity to improve IMCI assessments.

Hypoxemia - a low SpO2, is associated with increased mortality in children with LRI(1).4 Hypoxemia prevalence amongst children with pneumonia in African contexts has been estimated at 28%, and in outpatient settings as 23%.5 As hypoxemia is a key mortality risk factor, effectively identifying these children early in the care-seeking pathway is fundamental to reducing mortality in low-resource contexts.6 While SpO2 is recommended by IMCI for children with suspected pneumonia, pulse oximetry devices for measuring SpO2 are not widely implemented in PHCs in LMICs, where most children first access care. In Malawi 16% of nearly 700 outpatient encounters with suspected LRI had a SpO2 measured, and \>40% of children eligible for hospitalization were not referred. Since few children have SpO2 collected during outpatient care, referral decisions are largely based on subjective clinical danger signs. This then has knock-on effects on receipt of oxygen treatment.

While pulse oximetry implementation in PHCs has been slow to scale-up, there is evidence of utility and feasibility. In Malawi, healthcare workers successfully measured the SpO2 on 94% of \>14,000 children and were \>2 times more likely to correctly refer a child when the child's SpO2 was low. This work also demonstrated \>60% of hypoxemic children would not have been referred in the absence of an SpO2 measurement.7 One explanation for slow adoption is the lack of appropriate devices, that have been designed specifically for spot-checks amongst children in outpatient LMIC settings - a population with specific oximetry needs. Important features of such a device are being low cost, robust, able to cope with poor perfusion and motion artefact, good battery life and reliable.8

Mobile phones are relatively inexpensive, widely available, and increasingly utilized for healthcare - 'mobile Health (mHealth)', while electronic Health (eHealth) is when electronic services - like the internet - support healthcare. In LMICs mobile phones offer the potential for expanded healthcare access and quality of care both as a medical device and as a platform for eHealth services, such as the digital health management information system (HMIS) used in sub-Saharan Africa - District Health Information Software 2 (DHIS2). Developing a mobile-based pulse oximeter, with interoperability to store and upload data directly into a patients DHIS2 record has the potential to improve the management of paediatric hypoxaemia. The Phefumela Project, meaning "breathe" in a local South African language, will evaluate the impact of two different novel paediatric pulse oximeters, both designed specifically for this population in a high burden setting in South Africa.

Aim 1: Determine the impact of two novel paediatric pulse oximeter devices on the correct management of hypoxaemia.

Aim 2: Describe the burden of hypoxaemia and risks for mortality amongst children presenting with acute respiratory infections in a low-resource setting in Cape Town.

Setting:

The study site is the large Khayelitsha community, which includes 6 primary healthcare clinics (PHCs), 2 community health centers (CHCs), 1 community day centers (CDCs) and one government district hospital serving its catchment area, Khayelitsha Hospital. The nearest tertiary referral government hospital is Tygerberg, which serves 40% of the provincial paediatric population. Khayelitsha township has a population of approximately 450,000 and is 90.5% Black African. Khayelitsha has a very young population, with \>40% of its residents under 19 years of age, residing in informal housing with high caregiver unemployment and limited running water access. HIV (human immunodeficiency virus) and tuberculosis prevalence is high; maternal HIV prevalence is 29.5% - the highest in the Western Cape Province - and the tuberculosis incidence of 1,389/100,000 population exceeded the national average of 834/100,000 in 2017.9 Khayelitsha Hospital has an average bed occupancy rate over 130% capacity, and its 47 bed emergency center cares for about 120 patients daily. A 2015 study characterized the pediatric case mix over six months at the emergency center, reporting \>80% of pediatric patients were \<5 years old, nearly 2/3 were triaged at an emergent level, and the most common diagnosis was LRIs (22.0%, n=70/317). Of 58 children with pneumonia, 5 (8.5%) died.9

Pulse oximeter devices:

The investigators will be using and comparing three different pulse oximeter devices during this study, two (the Phefumla and Lifebox-01 (LB-01) are not commercially available. The Contec device is widely available and currently used clinically in this setting in South Africa. Throughout this study, the Contec device will be considered the reference or control standard.

Eligibility criteria: Inclusion Criteria:

* 0 to \<24 months of age inclusive
* presenting to care for an acute condition the includes observed and/or caregiver history of either cough and/or difficult breathing
* residing in clinic catchment area
* caregiver agrees to provide contact details including phone number and/or residential address
* caregiver agrees to be contacted after two weeks by the study staff
* caregiver is able and willing to provide written informed consent

Exclusion Criteria:

* 24 months of age or older
* presenting to care for a non-acute condition or an acute condition that does not include either observed or caregiver history of cough and/or difficult breathing
* does not reside in the clinic catchment area
* caregiver does not agree to provide contact details
* caregiver does not agree to be contact by study staff after two weeks
* caregiver unable to provide written informed consent

Primary outcomes:
measure: Proportion of Children with Correct management of oxygen saturation
timeFrame: Day 1
Secondary outcomes:
measure: Proportion of Children with Correct SpO2 management (definition 2)
timeFrame: Day 1
measure: Proportion of Children with Correct SpO2 management (definition 3)
timeFrame: Day 1
measure: Proportion of Children with Correct SpO2 management (definition 4)
timeFrame: Day 1
measure: Proportion of Children with Correct SpO2 management (definition 5)
timeFrame: Day 1
measure: Proportion of Children with Correct SpO2 management (definition 6)
timeFrame: Day 15 after enrollment
measure: Communication fidelity as assessed by number of participants who had timely communication
timeFrame: Day 1
measure: Proportion of plausible measurement (Quality measurement)
timeFrame: Day 1
measure: Feasibility as assessed by number of measurement attempts
timeFrame: Day 1
measure: Measurement acceptance as assessed by the proportion of caregivers who permit Sp02 measurement
timeFrame: Day 1
measure: Referral acceptance as assessed by proportion of children who present to hospital
timeFrame: Day 2
measure: Oxygen treatment as assessed by proportion of children who are given oxygen treatment
timeFrame: Day 2
measure: Treatment failure as assessed by proportion of children still feeling sick
timeFrame: Day 15
measure: Hypoxemia prevalence
timeFrame: Day 1
measure: Mortality
timeFrame: Day 15
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: Desmond Tutu TB Centre
state: Western Cape
Study officials:
affiliation: Johns Hopkins School of Medicine
name: Eric McCollum, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Reiner RC, Welgan CA, Casey DC, Troeger CE, Baumann MM, Nguyen QP, Swartz SJ, Blacker BF, Deshpande A, Mosser JF, Osgood-Zimmerman AE, Earl L, Marczak LB, Munro SB, Miller-Petrie MK, Rodgers Kemp G, Frostad J, Wiens KE, Lindstedt PA, Pigott DM, Dwyer-Lindgren L, Ross JM, Burstein R, Graetz N, Rao PC, Khalil IA, Davis Weaver N, Ray SE, Davis I, Farag T, Brady OJ, Kraemer MUG, Smith DL, Bhatt S, Weiss DJ, Gething PW, Kassebaum NJ, Mokdad AH, Murray CJL, Hay SI. Identifying residual hotspots and mapping lower respiratory infection morbidity and mortality in African children from 2000 to 2017. Nat Microbiol. 2019 Dec;4(12):2310-2318. doi: 10.1038/s41564-019-0562-y. Epub 2019 Sep 30.
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citation: McCollum ED, King C, Hammitt LL, Ginsburg AS, Colbourn T, Baqui AH, O'Brien KL. Reduction of childhood pneumonia mortality in the Sustainable Development era. Lancet Respir Med. 2016 Dec;4(12):932-933. doi: 10.1016/S2213-2600(16)30371-X. Epub 2016 Nov 12. No abstract available.
citation: McCollum ED, King C, Deula R, Zadutsa B, Mankhambo L, Nambiar B, Makwenda C, Masache G, Lufesi N, Mwansambo C, Costello A, Colbourn T. Pulse oximetry for children with pneumonia treated as outpatients in rural Malawi. Bull World Health Organ. 2016 Dec 1;94(12):893-902. doi: 10.2471/BLT.16.173401. Epub 2016 Oct 11.
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