Comparison of Oxygen Controllers in Preterm InfanTs (COCkPIT)

A Randomized Cross-over Trial in the Effect of Automated Oxygen Control Devices on the Distribution of Oxygen Saturation in Preterm Infants

Premature infants often receive respiratory support and supplemental oxygen for a prolonged period of time during their admission in the NICU. While maintaining the oxygen saturation within a narrow target range is important to prevent morbidity, manual oxygen titration can be very challenging. Automatic titration by a controller has been proven to be more effective. However, to date the performance of different controllers has not been compared. The proposed randomized crossover trial Comparing Oxygen Controllers in Preterm InfanTs (COCkPIT) is designed to compare the effect on time spent within target range. The results of this trial will help determining which algorithm is most successful in controlling oxygen, improve future developments in automated oxygen control and ultimately reduce the morbidity associated with hypoxemia and hyperoxemia.

Study Overview

• Status: Terminated
• Conditions: Hypoxia; Respiratory Insufficiency; Hyperoxia; Premature Infant
• Intervention / Treatment: Device: Automated oxygen control by the CLiO2 algorithm; Device: Automated oxygen control by the Oxygenie algorithm

Detailed Description

Both hypoxemia as hyperoxemia can potentially be harmful to premature infants. Oxygen titration during respiratory support is vital to prevent these conditions but is very challenging. In the investigator's neonatal intensive care unit preterm infants routinely receive automatic oxygen titration performed by a controller. The currently used controllers are both proven to be more effective than manual titration, however which of the two controllers is most effective in keeping oxygen saturation within target range remains unclear.

This randomized crossover trial tests tests both controllers within every study patient to determine which controller is most effective and thereby would hopefully reduce morbidity associated with hypoxemia and hyperoxemia the most. The primary outcome measure is the proportion of time spent within target range, each controller will be tested for 24 hours within the same study subject. This is excluding a 1-hour wash-out period after a change in ventilator.

Eligible infants are randomized to start with either the Oxygenie algorithm or CLiO2 algorithm and will switch to the other study arm after 24 hours of measurement.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands, 2333
      • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Preterm infants with a gestational age (GA) at birth of 24 - 29+6/7 weeks
• Receiving invasive mechanical ventilation or non-invasive respiratory support (NCPAP or NIPPV)
• Receiving supplemental oxygen (defined as FiO2 ≥ 0.25) at the time of enrollment and for at least 18 hours during the previous 24 hours; Or a coefficient of variation in supplemental oxygen of ≥ 0.1 in the previous 24 hours.
• Expected to complete the 49-hour or 50-hour study period in the current form of respiratory support, i.e. invasive mechanical ventilation or non-invasive respiratory support
• Written informed parental consent must be present.

Exclusion Criteria:

• Major congenital anomalies
• Arterial hypotension requiring vasopressor therapy within 48 hours prior to enrollment.
• If the attending physician considers the infant not stable enough for a switch to another ventilator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CLiO2; Automated oxygen control by the CLiO2 algorithm	Device: Automated oxygen control by the CLiO2 algorithm; Automated oxygen control for 24 hours by the CLiO2 algorithm, preceded by a 1 hour wash-out period; Other Names: AVEA CLiO2
Experimental: Oxygenie; Automated oxygen control by the Oxygenie algorithm	Device: Automated oxygen control by the Oxygenie algorithm; Automated oxygen control for 24 hours by the Oxygenie algorithm, in case of switch in ventilator preceded by a 1-hour wash-out period.; Other Names: SLE Oxygenie

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of time with SpO2 spent within set target range	Total time SpO2 is within the set target range (91-95%) including time spent above target range when in room air (set FiO2 < 0.22)	Continuously from randomization until study completion. (maximum of 50 hours) Measurements during wash-out periods (up to 1 hour after ventilator switch) will be excluded.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of time with SpO2 spent above target range (SpO2 > 95%)		Continuously from randomization until study completion. (maximum of 50 hours) Measurements during wash-out periods (up to 1 hour after ventilator switch) will be excluded.
Proportion of time with SpO2 spent below target range (SpO2 < 91%)		Continuously from randomization until study completion. (maximum of 50 hours) Measurements during wash-out periods (up to 1 hour after ventilator switch) will be excluded.
Coefficient of SpO2 variation		Continuously from randomization until study completion. (maximum of 50 hours) Measurements during wash-out periods (up to 1 hour after ventilator switch) will be excluded.
Time in hypoxemic SpO2 ranges	Time in SpO2 range 85-90%, 80-84% and <80%	Continuously from randomization until study completion. (maximum of 50 hours) Measurements during wash-out periods (up to 1 hour after ventilator switch) will be excluded.
Time in hyperoxemic SpO2 ranges	Time in SpO2 range 96-98% and >98%	Continuously from randomization until study completion. (maximum of 50 hours) Measurements during wash-out periods (up to 1 hour after ventilator switch) will be excluded.
Frequency of episodes of hypoxemia	Episodes in hypoxemia with SpO2 < 85% for ≥ 30 seconds, for ≥ 60 seconds and hypoxemia < 80% for ≥ 30 seconds and ≥ 60 seconds	Continuously from randomization until study completion. (maximum of 50 hours) Measurements during wash-out periods (up to 1 hour after ventilator switch) will be excluded.
Frequency of episodes of hyperoxemia	Episodes in hyperoxemia with SpO2 ≥ 97% for ≥ 30 seconds, for ≥ 60 seconds and hyperoxemia ≥ 99% for ≥ 30 seconds and ≥ 60 seconds	Continuously from randomization until study completion. (maximum of 50 hours) Measurements during wash-out periods (up to 1 hour after ventilator switch) will be excluded.
Frequency of episodes of bradycardia	Episodes where the heart rate < 100 beats per minute for ≥ 10 seconds	Continuously from randomization until study completion. (maximum of 50 hours) Measurements during wash-out periods (up to 1 hour after ventilator switch) will be excluded.
Frequency of FiO2 adjustments during automated control	FiO2 adjustments as made by the controller and by bedside staff as manual over-rides by the bedside staff as well	Continuously from randomization until study completion. (maximum of 50 hours) Measurements during wash-out periods (up to 1 hour after ventilator switch) will be excluded.
Average oxygen exposure		Continuously from randomization until study completion. (maximum of 50 hours) Measurements during wash-out periods (up to 1 hour after ventilator switch) will be excluded.
Coefficient of variation of FiO2		Continuously from randomization until study completion. (maximum of 50 hours) Measurements during wash-out periods (up to 1 hour after ventilator switch) will be excluded.
Effects on nursing workload in relation to FiO2 adjustment	Number of manual FiO2 adjustments and as the effect on workload measured by a translated questionnaire adapted from the NASA TLX questionnaire, using a visual rating scale	From randomization until study completion. (maximum of 50 hours) Manual adjustments during wash-out periods will be excluded.
Confidence of the bedside staff in the automated control system	Measured at the end of each nursing shift by a subset of questions out of the System Trust Scale (Jian et al. 2000) questionnaire. All questions are answered on a 1 (not at all) to 7 (extremely) scale.	From randomization until study completion. (maximum of 50 hours)

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: University of Tasmania
• Investigators: Principal Investigator: Arjan B te Pas, Prof, Leiden University Medical Center; Principal Investigator: Peter A Dargaville, Prof, University of Tasmania

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2019
• Primary Completion (Actual): February 13, 2020
• Study Completion (Actual): February 13, 2020

Study Registration Dates

• First Submitted: March 12, 2019
• First Submitted That Met QC Criteria: March 14, 2019
• First Posted (Actual): March 15, 2019

Study Record Updates

• Last Update Posted (Actual): June 9, 2020
• Last Update Submitted That Met QC Criteria: June 5, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Respiratory Insufficiency; Hypoxia; Hyperoxia
• Other Study ID Numbers: COCkPIT; NL66058.000.18 (Other Identifier: Dutch Central Committee on Research Involving Human Subjects)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No