Oxygen Therapy for Children With Moderate Hypoxemia in Malawi

Study Overview
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Brief Summary
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The goal of this pilot clinical trial is to compare standard of care, low-flow oxygen, and high-flow nasal canula oxygen in pediatric patients aged 1-59 months with pneumonia and an oxygen saturation of 90-93% in Malawi. The main question it aims to answer is: Does the protocol for the randomized control trial work well? Can the researchers safely conduct the protocol for the trial? Participants will be randomly assigned to one of the three groups (normal care without oxygen, low-flow oxygen, and high-flow nasal cannula oxygen) and treated with that therapy in the hospital. Researchers will look at the ability to safely conduct each part of the study.

Detailed Description
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Pneumonia is the leading infectious cause of under 5-year-old deaths globally and responsible for &gt;50% of deaths in Africa. The World Health Organization (WHO) defines low blood oxygen saturation (SpO2) levels (hypoxemia) as 90%. Hypoxemia is identified in 31% of child pneumonia cases in Africa and is a key marker of elevated mortality risk. When children are hypoxemic, the WHO recommends oxygen treatment. Importantly, the WHO threshold of 90% for hypoxemia was based on concerns over limited oxygen supply and hospital over-crowding in low- and middle-income countries (LMICs), rather than quality evidence. In most LMICs, low oxygen flow is the mainstay of oxygen delivery. Recently, in high-income settings high-flow nasal cannula (HFNC) oxygen has emerged as a safe and effective alternative. HFNC oxygen delivers higher flow warmed, humidified gas via nasal prongs to reverse hypoxemia, and potentially improve outcomes. Recent evidence challenges whether the WHO & 90% hypoxemia threshold is optimal for identifying all children at higher risk of mortality in LMICs. One meta-analysis from 13 LMICs reported 3.66-fold-higher odds of death (95% confidence interval (CI), 1.42, 9.47) for children with a SpO2 93%. The investigators research from Malawi and Bangladesh established children with pneumonia and SpO2 between 90-93% (moderate hypoxemia) is common, and, compared to higher SpO2 levels, conveys higher mortality risk. To date, African children with a SpO2 90-93% are not recommended for oxygen treatment. Observational data from Malawi found children with moderate hypoxemia and treated with oxygen had higher survival than those referred with a SpO2 90%. Currently, no randomized trials have determined whether low flow oxygen or HFNC oxygen treatment reduces the mortality of children with moderate hypoxemia (SpO2 90-93%) in African LMICs. Aim 1: Conduct a pilot open label, three armed, parallel, randomized controlled trial (RCT) comparing standard care, low-flow oxygen, and HFNC oxygen for children with clinical pneumonia and a SpO2 90-93% to determine feasibility of a larger trial. The investigators hypothesize it will be feasible to recruit, randomize, treat, and safely follow-up all participants. Children with SpO2 90-93% will be randomized 1:1:1 to standard care without oxygen (controls), low flow oxygen (intervention #1), or HFNC oxygen (intervention #2). The primary outcome will be feasibility, defined as the proportion of enrolled children with 2 protocol violations. Secondary outcomes include consent refusal, intervention efficacy, participant attrition, and safety. Aim 2: Determine the prevalence of young Malawian children with a SpO2 90-93% at the designated study hospital. The investigators hypothesize a SpO2 90-93% will be common among children presenting to the trial hospital. The investigators will measure the SpO2 of all children under-five years old (not limited to pneumonia cases) presenting to the hospital 1 week per month over 12-months. Conservatively assuming an average volume of 30 children per day, based on prior data, the investigators will generate 1,400 SpO2 measurements.

Official Title
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Oxygen Therapy for Children With Moderate Hypoxemia in Malawi: Pilot Randomized Control Trial

Conditions
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Pneumonia

Intervention / Treatment
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* Device: Low flow oxygen
* Device: High-flow nasal cannula oxygen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1-59 months of age Pneumonia (as defined by the World Health Organization) Oxygen saturation 90-93% without oxygen Exclusion Criteria: Emergency signs (signs of severe illness as defined by the World Health Organization) including: absent or obstructed breathing, severe respiratory distress, shock, decreased mental status, convulsions, or severe dehydration

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pilot trial to assess feasibility of the protocol for a three-armed, open-label randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of Care<br>Participants will receive pneumonia care per World Health Organization guidelines. If their oxygen saturation falls below 90% after enrollment, they will be treated with low-flow oxygen. | |
| Experimental: Low-flow Oxygen<br>Participants will be treated with low-flow oxygen to achieve a goal oxygen saturation above 94% | Device: Low flow oxygen<br>* Standard nasal cannula oxygen up to 2 liters/minute<br>|
| Experimental: High-flow Nasal Cannula Oxygen<br>Participants will be treated with high-flow nasal cannula oxygen to achieve a goal oxygen saturation above 94%. | Device: High-flow nasal cannula oxygen<br>* High-flow nasal cannula with heating and humidification up to 2 liters/kilogram/minute<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of study protocol as assessed by protocol violations | Determine overall protocol fidelity, defined as the percentage of enrolled children with < 2 protocol violations, of an open-label, three arm randomized controlled trial comparing low-flow and high-flow nasal cannula (HFNC) oxygen to standard of care without oxygen therapy | Enrollment up to 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Caregiver Trial Acceptability | Determine caregiver trial acceptability, defined as the percentage of caregivers of eligible children who consent to study participation. | Day of screening and enrollment | 
| Feasibility of screening and enrollment as assessed by percentage of inclusion and exclusion violations | Determine the feasibility of screening and enrollment, defined as the percentage of enrolled children with no inclusion or exclusion criteria violations. | Day of screening and enrollment | 
| Feasibility of randomization as assessed by percentage of children receiving intervention | Determine feasibility of randomization, defined as percentage of children actively receiving the assigned intervention within 1 hours of randomization | 1 hour after randomization | 
| Fidelity to treatment failure study definition as assessed by percentage of children with correct treatment failure classification | Determine fidelity to treatment failure study definition, defined as the percentage of children with a correct treatment failure classification | Enrollment up to 14 days | 
| Fidelity to respiratory supportive care protocol as assessed by percentage of children without a respiratory support protocol violation | Determine fidelity to respiratory supportive care protocol, defined as the proportion of children without a respiratory support protocol violation | Enrollment up to 14 days | 
| Feasibility of at home follow up as assessed by percentage of participants followed up at home | Determine feasibility of at home follow up defined as percentage of patients successfully followed up at home with assessment of vital status | Enrollment up to 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumonia, High flow nasal cannula oxygen, Oxygen, Low and Middle Income Countries, pediatrics