Clinical trial NCT06176664: Oxygen Therapy for Children With Moderate Hypoxemia in Malawi
Official title: Oxygen Therapy for Children With Moderate Hypoxemia in Malawi: Pilot Randomized Control Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pneumonia
Keywords: Pneumonia
High flow nasal cannula oxygen
Oxygen
Low and Middle Income Countries
pediatrics
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Thrasher Research Fund
First posted: 2023-12-20
Enrollment: 21
Sex: ALL
Minimum age (years): 1
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pilot trial to assess feasibility of the protocol for a three-armed, open-label randomized controlled trial
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Feasibility of study protocol as assessed by protocol violations
timeFrame: Enrollment up to 14 days
Secondary outcomes:
measure: Caregiver Trial Acceptability
timeFrame: Day of screening and enrollment
measure: Feasibility of screening and enrollment as assessed by percentage of inclusion and exclusion violations
timeFrame: Day of screening and enrollment
measure: Feasibility of randomization as assessed by percentage of children receiving intervention
timeFrame: 1 hour after randomization
measure: Fidelity to treatment failure study definition as assessed by percentage of children with correct treatment failure classification
timeFrame: Enrollment up to 14 days
measure: Fidelity to respiratory supportive care protocol as assessed by percentage of children without a respiratory support protocol violation
timeFrame: Enrollment up to 14 days
measure: Feasibility of at home follow up as assessed by percentage of participants followed up at home
timeFrame: Enrollment up to 14 days
Other outcomes:
measure: Treatment failure rate
timeFrame: Enrollment up to 14 days
measure: Mortality rate
timeFrame: Enrollment up to 14 days
measure: Number of Serious Adverse Events
timeFrame: Enrollment up to 14 days
measure: Hospital length of stay (days)
timeFrame: Enrollment through hospital discharge up to 30 days
Locations:
city: Salima
country: Malawi
facility: Salima District Hospital
state: Central Region
Study officials:
affiliation: Johns Hopkins School of Medicine
name: Eric E McCollom, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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