Automated Versus Manual Control Of Oxygen For Preterm Infants On Continuous Positive Airway Pressure In Nigeria

Prematurity Clinical Trial

Official title:

Automated Oxygen Control for Preterm Infants On Continuous Positive Airway Pressure (CPAP): Phase 1/2 Trial In Southwest Nigeria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05508308
• Other study ID #: HREC84704
• Status: Completed
• Phase: N/A
• Start date: September 13, 2022
• Est. completion date: September 29, 2023

Study information

• Verified date: November 2023
• Source: Murdoch Childrens Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: September 29, 2023
• Est. primary completion date: September 29, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Hours to 1 Month

Eligibility

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

Related Conditions & MeSH terms

• Neonatal Respiratory Distress Related Conditions
• Neonatal Respiratory Failure
• Oxygen Toxicity
• Prematurity
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Respiratory Insufficiency

Intervention

Device:
• OxyMate
Automated Oxygen Control algorithm (VDL 1.1) coupled with Diamedica Baby CPAP device

Other:
• Manual oxygen control
Guidelines and training in FiO2 titration to achieve a target range of SpO2. Health workers instructed in responding to continuous pulse oximetry readings and alarms

Locations

Country	Name	City	State
Nigeria	University College Hospital	Agodi	Ibadan
Nigeria	Sacred Heart Hospital	Lantoro	Abeokuta

Sponsors (5)

Lead Sponsor	Collaborator
Murdoch Childrens Research Institute	Sacred Heart Hospital Lantoro, University College Hospital, Ibadan, University of Ibadan, University of Tasmania

Country where clinical trial is conducted

Nigeria, 

References & Publications (16)

Askie LM, Darlow BA, Finer N, Schmidt B, Stenson B, Tarnow-Mordi W, Davis PG, Carlo WA, Brocklehurst P, Davies LC, Das A, Rich W, Gantz MG, Roberts RS, Whyte RK, Costantini L, Poets C, Asztalos E, Battin M, Halliday HL, Marlow N, Tin W, King A, Juszczak E — View Citation

BOOST-II Australia and United Kingdom Collaborative Groups; Tarnow-Mordi W, Stenson B, Kirby A, Juszczak E, Donoghoe M, Deshpande S, Morley C, King A, Doyle LW, Fleck BW, Davis PG, Halliday HL, Hague W, Cairns P, Darlow BA, Fielder AR, Gebski V, Marlow N, — View Citation

Chawanpaiboon S, Vogel JP, Moller AB, Lumbiganon P, Petzold M, Hogan D, Landoulsi S, Jampathong N, Kongwattanakul K, Laopaiboon M, Lewis C, Rattanakanokchai S, Teng DN, Thinkhamrop J, Watananirun K, Zhang J, Zhou W, Gulmezoglu AM. Global, regional, and na — View Citation

Dargaville PA, Marshall AP, Ladlow OJ, Bannink C, Jayakar R, Eastwood-Sutherland C, Lim K, Ali SKM, Gale TJ. Automated control of oxygen titration in preterm infants on non-invasive respiratory support. Arch Dis Child Fetal Neonatal Ed. 2022 Jan;107(1):39 — View Citation

Dargaville PA, Marshall AP, McLeod L, Salverda HH, Te Pas AB, Gale TJ. Automation of oxygen titration in preterm infants: Current evidence and future challenges. Early Hum Dev. 2021 Nov;162:105462. doi: 10.1016/j.earlhumdev.2021.105462. Epub 2021 Sep 4. — View Citation

Dargaville PA, Sadeghi Fathabadi O, Plottier GK, Lim K, Wheeler KI, Jayakar R, Gale TJ. Development and preclinical testing of an adaptive algorithm for automated control of inspired oxygen in the preterm infant. Arch Dis Child Fetal Neonatal Ed. 2017 Jan — View Citation

Gantz MG, Carlo WA, Finer NN, Rich W, Faix RG, Yoder BA, Walsh MC, Newman NS, Laptook A, Schibler K, Das A, Higgins RD; SUPPORT Study Group of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. A — View Citation

Gilbert C. Retinopathy of prematurity: a global perspective of the epidemics, population of babies at risk and implications for control. Early Hum Dev. 2008 Feb;84(2):77-82. doi: 10.1016/j.earlhumdev.2007.11.009. Epub 2008 Jan 29. — View Citation

Hagadorn JI, Furey AM, Nghiem TH, Schmid CH, Phelps DL, Pillers DA, Cole CH; AVIOx Study Group. Achieved versus intended pulse oximeter saturation in infants born less than 28 weeks' gestation: the AVIOx study. Pediatrics. 2006 Oct;118(4):1574-82. doi: 10 — View Citation

Mitra S, Singh B, El-Naggar W, McMillan DD. Automated versus manual control of inspired oxygen to target oxygen saturation in preterm infants: a systematic review and meta-analysis. J Perinatol. 2018 Apr;38(4):351-360. doi: 10.1038/s41372-017-0037-z. Epub — View Citation

Plottier GK, Wheeler KI, Ali SK, Fathabadi OS, Jayakar R, Gale TJ, Dargaville PA. Clinical evaluation of a novel adaptive algorithm for automated control of oxygen therapy in preterm infants on non-invasive respiratory support. Arch Dis Child Fetal Neonat — View Citation

Salverda HH, Cramer SJE, Witlox RSGM, Gale TJ, Dargaville PA, Pauws SC, Te Pas AB. Comparison of two devices for automated oxygen control in preterm infants: a randomised crossover trial. Arch Dis Child Fetal Neonatal Ed. 2022 Jan;107(1):20-25. doi: 10.11 — View Citation

Sink DW, Hope SA, Hagadorn JI. Nurse:patient ratio and achievement of oxygen saturation goals in premature infants. Arch Dis Child Fetal Neonatal Ed. 2011 Mar;96(2):F93-8. doi: 10.1136/adc.2009.178616. Epub 2010 Oct 30. — View Citation

Sturrock S, Williams E, Dassios T, Greenough A. Closed loop automated oxygen control in neonates-A review. Acta Paediatr. 2020 May;109(5):914-922. doi: 10.1111/apa.15089. Epub 2019 Nov 27. — View Citation

Walker PJB, Bakare AA, Ayede AI, Oluwafemi RO, Olubosede OA, Olafimihan IV, Tan K, Duke T, Falade AG, Graham H. Using intermittent pulse oximetry to guide neonatal oxygen therapy in a low-resource context. Arch Dis Child Fetal Neonatal Ed. 2020 May;105(3) — View Citation

WHO Recommendations on Interventions to Improve Preterm Birth Outcomes. Geneva: World Health Organization; 2015. Available from http://www.ncbi.nlm.nih.gov/books/NBK321160/ — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of time in target SpO2 range	Proportion of time (over total recorded time) in the target SpO2 range (91-95%, or 91-100% when in room air). Measured as %time	Measured for each 24 hour study epoch
Secondary	Proportion of time in target SpO2 range when receiving supplemental oxygen	Proportion of time (over total recorded time) in SpO2 target range (91-95%) when receiving supplemental oxygen. Measured as %time when receiving oxygen	Measured for each 24 hour study epoch
Secondary	Proportion of time in hypoxaemia	Proportion of time (over total recorded time) with SpO2<90% (hypoxaemia). Measured as %time	Measured for each 24 hour study epoch
Secondary	Proportion of time in severe hypoxaemia	Proportion of time (over total recorded time) with SpO2 <80% (severe hypoxaemia). Measured as %time	Measured for each 24 hour study epoch
Secondary	Frequency of prolonged hypoxaemia episodes	Frequency of 30 seconds episodes with SpO2 continuously <80% (severe hypoxaemic episodes). Measured as episodes per hour	Measured for each 24 hour study epoch
Secondary	Proportion of time in hyperoxaemia	Proportion of time (over total recorded time) with SpO2 >96% when receiving supplemental oxygen (hyperoxaemia). Measured as %time when receiving oxygen	Measured for each 24 hour study epoch
Secondary	Proportion of time in severe hyperoxaemia	Proportion of time (over total recorded time) with SpO2 >98% when receiving supplemental oxygen (severe hyperoxaemia). Measured as %time when receiving oxygen	Measured for each 24 hour study epoch
Secondary	Frequency of prolonged hyperoxaemia episodes	Frequency of 30 seconds episodes with SpO2 continuously >96% (hyperoxaemic episodes). Measured as episodes per hour	Measured for each 24 hour study epoch
Secondary	Manual FiO2 adjustments	Frequency of manual FiO2 adjustments. Measured as FiO2 adjustments/hour	Measured for each 24 hour study epoch
Secondary	No response to prolonged severe hypoxaemia (frequency)	Number of periods of no FiO2 increment for =30 seconds with SpO2 <80% (i.e. failure to respond to severe hypoxaemia). Measured as episodes per hour	Measured for each 24 hour study epoch
Secondary	No response to prolonged severe hypoxaemia (duration)	Duration of periods of no FiO2 increment for =30 seconds with SpO2 <80% (i.e. failure to respond to severe hypoxaemia). Measured as mean duration per episode	Measured for each 24 hour study epoch
Secondary	Severe hypoxaemia with bradycardia (frequency)	Number of periods with SpO2 <80% for =30 seconds with any bradycardia (heart rate <100 bpm). Measured as episodes per hour	Measured for each 24 hour study epoch
Secondary	Severe hypoxaemia with bradycardia (duration)	Duration of periods with SpO2 <80% for =30 seconds with any bradycardia (heart rate <100 bpm). Measured as mean duration per episode	Measured for each 24 hour study epoch
Secondary	Device malfunction	Number of OxyMate malfunction events	Measured through to OxyMate study completion: estimated 20 weeks
Secondary	Acceptability and usability	Mean/median user acceptability score (total and per question) on Likert scale from structured questionnaire. Scores range from 1 (strongly disagree) to 5 (strongly agree) with posed statement or question	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
Secondary	Costs	Total costs of prototype system (Diamedica +/- Automated Oxygen control - OxyMate)	Measured at completion of OxyMate study: an estimated 20 weeks
Secondary	Duration of CPAP and oxygen therapy	Duration of time on CPAP with supplemental oxygen. Measured in hours	Completed for each participant at end of their study period: 49 hours from study commencement
Secondary	CPAP in room air	Duration of time on CPAP in room air. Measured in hours	Completed for each participant at end of their study period: 49 hours from study commencement
Secondary	Time on low flow oxygen	Duration of time on low-flow oxygen therapy. Measured in hours	Completed for each participant at end of their study period: 49 hours from study commencement
Secondary	Final discharge outcome	Measured as categorical outcome (died in hospital, discharged well, discharged against medical advice, other)	Up to 4 weeks post enrollment
Secondary	Length of stay	Measured in days	Up to 4 weeks post enrollment