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

NCT05508308 | Completed DMC

• 1 other identifier: HREC84704
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 2

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.

Conditions

Neonatal Respiratory Distress Related Conditions; Neonatal Respiratory Failure; Prematurity; Oxygen Toxicity

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (20)

• Proportion of time in target SpO2 range when receiving supplemental oxygen

  Measured for each 24 hour study epoch

• Proportion of time in hypoxaemia

  Measured for each 24 hour study epoch

• Proportion of time in severe hypoxaemia

  Measured for each 24 hour study epoch

• Frequency of prolonged hypoxaemia episodes

  Measured for each 24 hour study epoch

• Proportion of time in hyperoxaemia

  Measured for each 24 hour study epoch

Study Arms (2)

Manual oxygen control

ACTIVE COMPARATOR

Oxygen therapy delivered with bCPAP as per standard practice, except for the addition of continuous pulse oximetry. Nursing staff will make manual adjustments to Fraction of Inspired Oxygen (FiO2) provided to infants on bCPAP. Oxygen saturations (SpO2) will be monitored by continuous pulse oximetry, and nurses asked to target the range of SpO2 91-95%. Pulse oximeter alarms will be set to alert nurses to periods of hypoxaemia (SpO2\<88%) and hyperoxaemia (SpO2\>96%).

Other: Manual oxygen control

OxyMate Automated Oxygen Control

EXPERIMENTAL

Automated control of oxygen therapy partnered with bCPAP delivered as per standard practice. The automated oxygen control set-up (OxyMate) will consist of: continuous pulse oximetry input, a computer algorithm (VDL1.1) that calculates changes to delivered FiO2 based on the input SpO2, and a mechanism to automatically effect changes to delivered FiO2. The system will target an SpO2 of 93% (mid-point of the target range). There will be several embedded safety mechanisms, including the ability to manually over-ride OxyMate at any stage. Pulse oximeter alarms will be as for the manual control arm, with additional automated system alarms in place.

Device: OxyMate

Interventions

OxyMate DEVICE

Automated Oxygen Control algorithm (VDL 1.1) coupled with Diamedica Baby CPAP device

OxyMate Automated Oxygen Control

Manual oxygen control OTHER

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

Manual oxygen control

Eligibility Criteria

• Age: 12 Hours - 1 Month
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \<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

You may not qualify if:

• 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

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead
• University of Tasmania: collaborator
• University College Hospital, Ibadan: collaborator
• Sacred Heart Hospital Lantoro: collaborator
• University of Ibadan: collaborator

Study Sites (2)

Sacred Heart Hospital

Lantoro, Abeokuta, 111101, Nigeria

Location

University College Hospital

Agodi, Ibadan, 200285, Nigeria

Location

Related Publications (17)

• 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 national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. Lancet Glob Health. 2019 Jan;7(1):e37-e46. doi: 10.1016/S2214-109X(18)30451-0. Epub 2018 Oct 30.

  PMID: 30389451 RESULT

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

  PMID: 26447264 RESULT

• 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.

  PMID: 18234457 RESULT

• 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, Simmer K, Tin W, Ghadge A, Williams C, Keech A, Wardle SP, Kecskes Z, Kluckow M, Gole G, Evans N, Malcolm G, Luig M, Wright I, Stack J, Tan K, Pritchard M, Gray PH, Morris S, Headley B, Dargaville P, Simes RJ, Brocklehurst P. Outcomes of Two Trials of Oxygen-Saturation Targets in Preterm Infants. N Engl J Med. 2016 Feb 25;374(8):749-60. doi: 10.1056/NEJMoa1514212. Epub 2016 Feb 10.

  PMID: 26863265 RESULT

• 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, Morley CJ, Doyle LW, Gebski V, Hunter KE, Simes RJ; Neonatal Oxygenation Prospective Meta-analysis (NeOProM) Collaboration. Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA. 2018 Jun 5;319(21):2190-2201. doi: 10.1001/jama.2018.5725.

  PMID: 29872859 RESULT

• 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.

  PMID: 21037284 RESULT

• 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. Achieved oxygen saturations and retinopathy of prematurity in extreme preterms. Arch Dis Child Fetal Neonatal Ed. 2020 Mar;105(2):138-144. doi: 10.1136/archdischild-2018-316464. Epub 2019 Jun 22.

  PMID: 31229956 RESULT

• 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: 10.1542/peds.2005-0413.

  PMID: 17015549 RESULT

• 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):316-321. doi: 10.1136/archdischild-2019-317630. Epub 2019 Aug 28.

  PMID: 31462405 RESULT

• 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.

  PMID: 31715041 RESULT

• 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 2018 Jan 2.

  PMID: 29296004 RESULT

• 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.

  PMID: 34511288 RESULT

• 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: 10.1136/archdischild-2020-321387. Epub 2021 Jun 10.

  PMID: 34112721 RESULT

• 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 Neonatal Ed. 2017 Jan;102(1):F37-F43. doi: 10.1136/archdischild-2016-310647. Epub 2016 Aug 29.

  PMID: 27573518 RESULT

• 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;102(1):F31-F36. doi: 10.1136/archdischild-2016-310650. Epub 2016 Sep 15.

  PMID: 27634820 RESULT

• 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):39-44. doi: 10.1136/archdischild-2020-321538. Epub 2021 May 7.

  PMID: 33963005 RESULT

• Subhi R, McLeod L, Ayede AI, Dedeke IO, Risikat Q, Akanbi AR, Fasasi AB, Bakare AA, Adeniyi OH, Akinrinoye O, Adeigbe O, Dargaville GF, Walker P, Grobler AC, Mosebolatan O, Badurdeen S, Gale TJ, Falade AG, Dargaville PA, Graham HR. Automated oxygen control for preterm infants receiving continuous positive airway pressure in southwest Nigeria: an open-label, randomised, crossover trial. Lancet Glob Health. 2025 Feb;13(2):e246-e255. doi: 10.1016/S2214-109X(24)00458-3.

  PMID: 39890225 DERIVED

MeSH Terms

Conditions

Premature Birth

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Hamish R Graham, PhD

  Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 12, 2022
• First Posted: August 19, 2022
• Study Start: September 13, 2022
• Primary Completion: September 29, 2023
• Study Completion: September 29, 2023
• Last Updated: November 13, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: 2 months after publication of the primary outcome.
• Access Criteria: Prior to releasing any data the following are required: 1. A Data Transfer Agreement must be signed between relevant parties. 2. The MCRI Sponsorship Committee must review and approve your protocol and statistical analysis plan which must include and describe how the data will be used and analysed. 3. An Authorship Agreement must be agreed to and signed between relevant parties. The Agreement must include details regarding appropriate recognition. Authorship may not be justifiable but some form of acknowledgment is requested. 4. Agreement to cover any additional costs relating to the provision of the data. 5. Evidence of ethics approval or waiver of approval, to be compliant with the data transfer agreement and ethics requirement at MCRI. Data will only be shared with a recognised research institution where the MCRI Sponsorship Committee has approved the proposed analysis plan.

Locations

NG (2)