Clinical trial NCT05508308: Automated Versus Manual Control Of Oxygen For Preterm Infants On Continuous Positive Airway Pressure In Nigeria
Official title: Automated Oxygen Control for Preterm Infants On Continuous Positive Airway Pressure (CPAP): Phase 1/2 Trial In Southwest Nigeria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Neonatal Respiratory Distress Related Conditions
Neonatal Respiratory Failure
Prematurity
Oxygen Toxicity
Lead sponsor: Murdoch Childrens Research Institute
Sponsor class: OTHER
Collaborators: name: University of Tasmania
name: University College Hospital, Ibadan
name: Sacred Heart Hospital Lantoro
name: University of Ibadan
First posted: 2022-08-19
Enrollment: 49
Sex: ALL
Minimum age (years): 12
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Preterm infants on bCPAP are managed with each mode of oxygen control for 24 hours, prior to crossing over to the other mode of control. Change over simply involves flicking the computer switch from manual to automated control (or vice versa) and it is enacted immediately. It does not require any adjustment or interruption of the CPAP and it does not involve additional action from clinical staff. While the fraction of inspired oxygen (FiO2) adjustments have their effect relatively rapidly, we will apply a 1 h washout period (dropping this data from analysis) to avoid contamination between arms.
Primary purpose: TREATMENT

Brief summary: One in ten babies are born preterm (\<37 weeks gestation) globally. Complications of prematurity are the leading cause of death in children under 5 years, with the highest mortality rate in Sub-Saharan Africa (SSA). Low flow oxygen, and respiratory support - where an oxygen/air mixture is delivered under pressure - are life saving therapies for these babies. Bubble Continuous Positive Airway Pressure (bCPAP) is the mainstay of neonatal respiratory support in SSA.

Oxygen in excess can damage the immature eyes (Retinopathy of Prematurity \[ROP\]) and lungs (Chronic Lung Disease) of preterm babies. Historically, in well-resourced settings, excessive oxygen administration to newborns has been associated with 'epidemics' of ROP associated blindness. Today, with increasing survival of preterm babies in SSA, and increasing access to oxygen and bCPAP, there are concerns about an emerging epidemic of ROP. Manually adjusting the amount of oxygen provided to an infant on bCPAP is difficult, and fearing the risks of hypoxaemia (low oxygen levels) busy health workers often accept hyperoxaemia (excessive oxygen levels). Some well resourced neonatal intensive care units globally have adopted Automated Oxygen Control (AOC), where a computer uses a baby's oxygen saturation by pulse oximetry (SpO2) to frequently adjust how much oxygen is provided, targetting a safe SpO2 range. This technology has never been tested in SSA, or partnered with bCPAP devices that would be more appropriate for SSA.

This study aims to compare AOC coupled with a low cost and robust bCPAP device (Diamedica Baby CPAP) - OxyMate - with manual control of oxygen for preterm babies on bCPAP in two hospitals in south west Nigeria. The hypothesis is that OxyMate can significantly and safely increase the proportion of time preterm infants on bCPAP spend in safe oxygen saturation levels.

Detailed description: Trial description: A randomised cross-over trial of manual versus automated control of oxygen (OxyMate) for preterm infants on bCPAP. This trial will use an established technology (automated oxygen titration algorithm, VDL1.1) partnered with a low-cost bCPAP device in a low-resource setting. It will involve preterm infants requiring bCPAP respiratory support with allocation to OxyMate or manual oxygen control for consecutive 24 h periods in random sequence.

Objectives: This trial seeks to examine safety and potential efficacy of our automated oxygen configuration (OxyMate) in preterm infants in a setting characterised by financial constraints, workforce limitations, and underdeveloped infrastructure, and assess contextual feasibility and appropriateness to inform future definitive clinical trials and product development.

Eligibility criteria: Inclusion Criteria:

* \<34 weeks gestation (or birth weight \< 2kg if gestation not known)
* ≥12 hours old
* Receiving CPAP support and supplemental oxygen (FiO2 \>0.21) for respiratory insufficiency
* Projected requirement for CPAP and oxygen therapy for \> 48 hours

Exclusion Criteria:

* Deemed likely to fail CPAP in the next 48 hours
* Deemed clinically unstable or recommended for palliation by treating team
* Cause of hypoxaemia likely to be non-respiratory - e.g. cyanotic heart disease
* Informed consent from parent/guardians not obtained

Primary outcomes:
measure: Proportion of time in target SpO2 range
timeFrame: Measured for each 24 hour study epoch
Secondary outcomes:
measure: Proportion of time in target SpO2 range when receiving supplemental oxygen
timeFrame: Measured for each 24 hour study epoch
measure: Proportion of time in hypoxaemia
timeFrame: Measured for each 24 hour study epoch
measure: Proportion of time in severe hypoxaemia
timeFrame: Measured for each 24 hour study epoch
measure: Frequency of prolonged hypoxaemia episodes
timeFrame: Measured for each 24 hour study epoch
measure: Proportion of time in hyperoxaemia
timeFrame: Measured for each 24 hour study epoch
measure: Proportion of time in severe hyperoxaemia
timeFrame: Measured for each 24 hour study epoch
measure: Frequency of prolonged hyperoxaemia episodes
timeFrame: Measured for each 24 hour study epoch
measure: Manual FiO2 adjustments
timeFrame: Measured for each 24 hour study epoch
measure: No response to prolonged severe hypoxaemia (frequency)
timeFrame: Measured for each 24 hour study epoch
measure: No response to prolonged severe hypoxaemia (duration)
timeFrame: Measured for each 24 hour study epoch
measure: Severe hypoxaemia with bradycardia (frequency)
timeFrame: Measured for each 24 hour study epoch
measure: Severe hypoxaemia with bradycardia (duration)
timeFrame: Measured for each 24 hour study epoch
measure: Device malfunction
timeFrame: Measured through to OxyMate study completion: estimated 20 weeks
measure: Acceptability and usability
timeFrame: Completed for each participant (health workers) at end of an infant's study period (49 hours). Results recorded for unique health workers through to OxyMate study completion: estimated 20 weeks
measure: Costs
timeFrame: Measured at completion of OxyMate study: an estimated 20 weeks
measure: Duration of CPAP and oxygen therapy
timeFrame: Completed for each participant at end of their study period: 49 hours from study commencement
measure: CPAP in room air
timeFrame: Completed for each participant at end of their study period: 49 hours from study commencement
measure: Time on low flow oxygen
timeFrame: Completed for each participant at end of their study period: 49 hours from study commencement
measure: Final discharge outcome
timeFrame: Up to 4 weeks post enrollment
measure: Length of stay
timeFrame: Up to 4 weeks post enrollment
Other outcomes:
Locations:
city: Lantoro
country: Nigeria
facility: Sacred Heart Hospital
state: Abeokuta
city: Agodi
country: Nigeria
facility: University College Hospital
state: Ibadan
Study officials:
affiliation: Murdoch Childrens Research Institute
name: Hamish R Graham, PhD
role: PRINCIPAL_INVESTIGATOR
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