Clinical trial NCT05030337: Optimising Ventilation in Preterms With Closed-loop Oxygen Control
Official title: Does Closed-loop Automated Oxygen Control Reduce the Duration of Mechanical Ventilation? A Randomised Controlled Trial in Ventilated Preterm Infants
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Infant, Premature, Diseases
Airway Morbidity
Mechanical Ventilation Complication
Lead sponsor: King's College Hospital NHS Trust
Sponsor class: OTHER
Collaborators: name: King's College London
First posted: 2021-09-01
Enrollment: 70
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participating infants will be randomised either to manual oxygen control or closed-loop automated oxygen control, adjusted by clinical staff as necessary.
Primary purpose: OTHER

Brief summary: Many premature infants require respiratory support in the newborn period. Mechanical ventilation although life-saving is linked to complications for the lungs and other organs and its duration should be kept to a minimum. The use of supplemental oxygen may also increase the risk of comorbidities such as retinopathy of prematurity. Therefore, oxygen saturation levels and the amount of inspired oxygen concentration provided should be continuously monitored.

Oxygen control can be performed manually or with the use of a computer software incorporated into the ventilator that is called 'closed loop automated oxygen control'(CLAC). The software uses an algorithm that automatically adjusts the amount of inspired oxygen to maintain oxygen saturation levels in a target range. Evidence suggests that CLAC increases the time spent in the desired oxygen target range but there are no data to determine the effect on important clinical outcomes. A previous study has also demonstrated that CLAC reduces the inspired oxygen concentration more rapidly when compared to manual control. That could help infants come off the ventilator sooner.

With this study we want to compare the time preterm infants spend on the ventilator when we use the software to automatically monitor their oxygen levels with those infants whose oxygen is adjusted manually by the clinical team. That could help us understand if the use of automated oxygen control reduces the duration of mechanical ventilation and subsequently the complications related to it.

Detailed description: This will be a randomised controlled trial. The investigators aim to recruit a minimum of seventy premature ventilated infants born at less than 31 weeks gestation. Participants will be randomised to either closed-loop automated oxygen control or manually controlled oxygen from recruitment to successful extubation. The investigators will also record basic epidemiologic parameters and associated comorbidities that may impact on the duration of mechanical ventilation. Infants with known congenital anomalies will be excluded from the study.

Informed written consent will be requested from the parents or legal guardians of the infants and the attending Neonatal Consultant will be requested to assent to the study.

Eligible infants whose parents consent to the study will be enrolled within 48 hours of initiation of mechanical ventilation.

Randomisation will be performed using an online randomisation generator. Patients will be ventilated using SLE6000 ventilators. Ventilation settings will be manually adjusted by the clinical team as per unit's protocol. The intervention group, in addition to standard care will be also connected to the OxyGenie closed-loop oxygen saturation monitoring software (SLE). This software uses oxygen saturations from the SpO2 probe attached to the neonate, fed into an algorithm, to automatically adjust the percentage of inspired oxygen to maintain oxygen saturations within the target range. Manual adjustments including the percentage of FiO2 will be allowed at any point during the study if deemed appropriate by the clinical team.

The nurse-to-patient ratio will be according to the unit's protocol that is determined on the patient's acuity.

Patients will be studied from enrolment until successful extubation. If an infant fails extubation and requires reintubation within 48 hours, he will be studied in his initial arm if less than 28 days old. Therefore, for those infants randomised at the intervention group CLAC will resume. Preterm infants that remain ventilated beyond day 28 of life will continue at their study arm (closed-loop automated oxygen control or manual oxygen control) till their first extubation attempt.

Eligibility criteria: Inclusion Criteria:

* Preterm infants less than 31 weeks completed gestation at birth requiring mechanical ventilation and admitted to King's NICU in the first 48 hours after birth

Exclusion Criteria:

* Preterm infants above 31 weeks completed gestation or term born infants
* Infants with major congenital abnormalities

Primary outcomes:
measure: The duration of mechanical ventilation
timeFrame: Through study completion, an average of 2 years
Secondary outcomes:
measure: The percentage of time spent within target oxygen saturation range.
timeFrame: Through study completion, an average of 2 years
measure: Number of manual adjustments to the inspired oxygen concentration required by clinical staff.
timeFrame: Through study completion, an average of 2 years
measure: Number of days on oxygen.
timeFrame: Through study completion, an average of 2 years
measure: Length of Intensive Care stay
timeFrame: Through study completion, an average of 2 years
measure: A diagnosis of bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age
timeFrame: Through study completion, an average of 2 years
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
Study officials:
affiliation: King's College Hospital/ King's College London
name: Anne Greenough, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Greenough A. Long-term respiratory consequences of premature birth at less than 32 weeks of gestation. Early Hum Dev. 2013 Oct;89 Suppl 2:S25-7. doi: 10.1016/j.earlhumdev.2013.07.004. Epub 2013 Jul 30.
citation: Di Fiore JM, Bloom JN, Orge F, Schutt A, Schluchter M, Cheruvu VK, Walsh M, Finer N, Martin RJ. A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity. J Pediatr. 2010 Jul;157(1):69-73. doi: 10.1016/j.jpeds.2010.01.046. Epub 2010 Mar 20.
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: 10.1542/peds.2005-0413.
citation: Ford SP, Leick-Rude MK, Meinert KA, Anderson B, Sheehan MB, Haney BM, Leeks SR, Simon SD, Jackson JK. Overcoming barriers to oxygen saturation targeting. Pediatrics. 2006 Nov;118 Suppl 2:S177-86. doi: 10.1542/peds.2006-0913P.
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.
citation: Sturrock S, Ambulkar H, Williams EE, Sweeney S, Bednarczuk NF, Dassios T, Greenough A. A randomised crossover trial of closed loop automated oxygen control in preterm, ventilated infants. Acta Paediatr. 2021 Mar;110(3):833-837. doi: 10.1111/apa.15585. Epub 2020 Oct 6.
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.
citation: Dani C. Automated control of inspired oxygen (FiO2 ) in preterm infants: Literature review. Pediatr Pulmonol. 2019 Mar;54(3):358-363. doi: 10.1002/ppul.24238. Epub 2019 Jan 10.
citation: Hunt KA, Dassios T, Ali K, Greenough A. Prediction of bronchopulmonary dysplasia development. Arch Dis Child Fetal Neonatal Ed. 2018 Nov;103(6):F598-F599. doi: 10.1136/archdischild-2018-315343. Epub 2018 Jun 12. No abstract available.
citation: Dimitriou G, Greenough A, Endo A, Cherian S, Rafferty GF. Prediction of extubation failure in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2002 Jan;86(1):F32-5. doi: 10.1136/fn.86.1.f32.
citation: Vliegenthart RJS, van Kaam AH, Aarnoudse-Moens CSH, van Wassenaer AG, Onland W. Duration of mechanical ventilation and neurodevelopment in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2019 Nov;104(6):F631-F635. doi: 10.1136/archdischild-2018-315993. Epub 2019 Mar 20.
citation: Kaltsogianni O, Dassios T, Greenough A. Does closed-loop automated oxygen control reduce the duration of mechanical ventilation? A randomised controlled trial in ventilated preterm infants. Trials. 2022 Apr 8;23(1):276. doi: 10.1186/s13063-022-06222-y.