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| Name | Class |
|---|---|
| University of Tasmania | OTHER |
| University College Hospital, Ibadan | OTHER |
| Sacred Heart Hospital Lantoro | UNKNOWN |
| University of Ibadan |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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%). |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| OxyMate | Device | Automated Oxygen Control algorithm (VDL 1.1) coupled with Diamedica Baby CPAP device |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Proportion of time in hypoxaemia |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hamish R Graham, PhD | Murdoch Childrens Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sacred Heart Hospital | Lantoro | Abeokuta | 111101 | Nigeria | ||
| University College Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30389451 | Result | 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. | |
| 26447264 |
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The de-identified data set collected for the final analysis of the OxyMate trial will be available two months after publication of the primary outcome.
Documents that will be made available are Study Protocol and Informed Consent Form. Data may be obtained from the Murdoch Children's Research Institute (MCRI) by emailing hamish.graham@mcri.edu.au and mctc@mcri.edu.au
2 months after publication of the primary outcome.
Prior to releasing any data the following are required:
Data will only be shared with a recognised research institution where the MCRI Sponsorship Committee has approved the proposed analysis plan.
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| OTHER |
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.
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| 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 |
|
Proportion of time (over total recorded time) with SpO2<90% (hypoxaemia). Measured as %time |
| Measured for each 24 hour study epoch |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Manual FiO2 adjustments | Frequency of manual FiO2 adjustments. Measured as FiO2 adjustments/hour | Measured for each 24 hour study epoch |
| 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 |
| 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 |
| 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 |
| 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 |
| Device malfunction | Number of OxyMate malfunction events | Measured through to OxyMate study completion: estimated 20 weeks |
| 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 |
| Costs | Total costs of prototype system (Diamedica +/- Automated Oxygen control - OxyMate) | Measured at completion of OxyMate study: an estimated 20 weeks |
| 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 |
| 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 |
| 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 |
| Final discharge outcome | Measured as categorical outcome (died in hospital, discharged well, discharged against medical advice, other) | Up to 4 weeks post enrollment |
| Length of stay | Measured in days | Up to 4 weeks post enrollment |
| Agodi |
| Ibadan |
| 200285 |
| Nigeria |
| 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/ |
| 18234457 | 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. |
| 26863265 | 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. |
| 29872859 | 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. |
| 21037284 | 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. |
| 31229956 | 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. |
| 17015549 | 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. |
| 31462405 | 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. |
| 31715041 | 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. |
| 29296004 | 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. |
| 34511288 | 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. |
| 34112721 | 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. |
| 27573518 | 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. |
| 27634820 | 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. |
| 33963005 | 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. |
| 39890225 | Derived | 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. |
| ID | Term |
|---|---|
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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