Automatic Oxygen Control for Reducing Extremes of Oxygen Saturation (AreOS): A Randomised Control Trial (AreOS)

July 14, 2022 updated by: South Tees Hospitals NHS Foundation Trust

Oxygen treatment is common in babies born early (preterm) and requiring intensive care. Having too much or too little oxygen can increase the risk of damage to the eyes and lungs, and contribute to death or disability. Preterm infants because of their immaturity experience episodes of low oxygen levels. The low oxygen episodes are primarily due to pauses in their breathing (Apnoea of prematurity) and immaturity of their lung. These episodes persist for weeks. The lower the gestation at birth the longer the duration of these events. Studies have shown that these episodes of low oxygen saturations especially if frequent and prolonged is associated with poor developmental outcome, severe eye disease and lung disease.

Traditionally, the oxygen delivery is manually adjusted when infant has low oxygen saturation. However previous studies have shown despite the best efforts the oxygen level can only be maintained less than half of the time and nearly a one-fifth of the time infant spends in low oxygen levels and nearly one third of the time in high oxygen levels. Now it is possible to maintain oxygen level in target range by using automatic control of oxygen delivery. With the proposed study, we would like to study the efficacy of automatic control of oxygen delivery in reducing the time spent in low oxygen levels.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Supplemental oxygen remains by far the most commonly used 'drug' in neonatal intensive care units. The goal of oxygen therapy is to maintain normal oxygenation while minimizing hypoxemia and hypoxemia. Preterm infants are particularly vulnerable to oxygen toxicity and oxidative stress leading to retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and periventricular leukomalacia (PVL)[1]. It's also well known that preterm infants experience hypoxic events which are primarily linked to cardiovascular instability and apnea of prematurity. These events vary as the infant matures. Martin R et al showed in their study that these hypoxic events peaked around 2-4 weeks and decreases by 6-8 weeks in preterm infants (2). Exposure to prolonged and frequent hypoxemic episodes has been associated with increased morbidity and mortality [3-5]. Prolonged hypoxic events (Saturation less than 80% for more than 1 minute) have been associated with severe ROP and impaired neurodevelopmental outcome in survivors (2, 5).

Peripheral oxygen saturation monitoring is standard of care in preterm infants. Traditionally oxygen saturation (SpO2) targeting is carried out by manual adjustment of fraction of inspired oxygen (FiO2) by the caregiver based on the monitored oxygen saturation. However, in practice this is only partially achieved during routine care[6]. Hagadorn et al conducted a study in 14 centers and showed that preterm infants under 28 weeks' gestation receiving oxygen spent on average only 48% of the time with SpO2 within the prescribed target range, about 36% of the time above and 16% of the time with SpO2 below the target range [7].

Preterm infants have frequent fluctuations in SpO2 due to their cardio-respiratory instability requiring frequent adjustments of FiO2 [7]. Consequently, these particularly vulnerable infants spend significant time with SpO2 outside intended range and are often exposed to extremes of hypoxemia and hyperoxaemia. It is now possible to have automated control of inspired oxygen using a device (CLiO2™) incorporated in Avea® ventilator. The device continuously monitors the oxygen saturation and adjusts the oxygen delivery to maintain oxygen saturation within the target range. The safety, feasibility and efficacy of this device have already been established [9-14]. There has been further improvement in the algorithm of the pulse oximeter incorporated in Avea® ventilator to achieve a better normative distribution around the median SpO2 value[15]. Automated control of FiO2 significantly improves compliance of oxygen saturation targeting and significantly reduces exposure to hypoxemia as well as hyperoxaemia [9-14, 16,]. Automatic control of oxygen delivery is available in both invasive and non-invasive mode of ventilation (17). The Avea ventilators are equipped with Automatic Oxygen control with invasive as well as non-invasive mode of ventilation.

Previous studies looking at the efficacy of automated oxygen control mostly have been a crossover model and the study duration less than 48 hours. As previously mentioned, preterm infants experience hypoxic events for few weeks before cardiopulmonary maturation is established. Hence, it's important to study these events over a longer period of time. The objective of this randomised controlled trial is to evaluate the efficacy of the automatic oxygen control function in reducing the time spent in extremes of oxygen saturations (less than 80%), in preterm infants for the entire period of their respiratory support on invasive or non-invasive mode of ventilation.

Study Type

Interventional

Enrollment (Actual)

44

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Middlesbrough, United Kingdom, TS4 3BW
        • South Tees NHS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 months to 7 months (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Preterm infants less than 33 weeks (23+0 to 32+6 weeks)

• Receiving invasive or non-invasive mode of respiratory support

Exclusion Criteria:

  • Infants more than or equal to 33 weeks
  • Preterm infants with congenital anomalies
  • Infants on a non-conventional mode of invasive or non-invasive ventilation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Automatic Oxygen Control
Infants randomized to this arm will be monitored using automatic oxygen control system on the ventilator. When infants oxygen saturation are out of the target range the ventilator will adjust the oxygen delivery depending on the saturation of the infant to bring the saturation int he target range.
Device: Automatic Oxygen control
The CLiO device is integral to the Avea infant ventilator and allows automated OXYGEN adjustment aiming to maintain SpO2 within assigned target range using neonatal pulse oximeter. When first started it adopts the FiO2 previously set by the clinician as the initial 'Baseline FiO2' level. Thereafter, the changes to the FiO2 and their frequency depend on whether SpO2 is below, above or within the target range, the trend in SpO2 and all changes are proportionate to the 'Baseline FiO2' level.
ACTIVE_COMPARATOR: Manual oxygen control
Infants randomized to this arm will be receive oxygen delivery adjustments manually by the nursing and medical team taking care of the infants. When the infants oxygen saturation are out of the target range, the staff will manually adjust the oxygen delivery.
Other: Manual Oxygen Control
In the manual arm the oxygen is adjusted manually by the clinical team.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
proportion of time spent in extreme saturation ( less than or equal to 80%)
Time Frame: Through study completion, an average of 8 weeks
The primary outcome of this study is proportion of time spent in extreme saturation (less than or equal to 80%) in preterm infants <33 weeks receiving invasive or non-invasive form of respiratory support.
Through study completion, an average of 8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of time spent in target saturation
Time Frame: Through study completion, an average of 8 weeks
Proportion of the time spent in target saturation of 90-95%
Through study completion, an average of 8 weeks
Proportion of time spent in saturation more than or equal to 98%
Time Frame: Through study completion, an average of 8 weeks
The proportion of time spent in more than or equal to 98% through the entire period of respiratory support
Through study completion, an average of 8 weeks
Number of episodes of prolonged hypoxemia (SpO2 less than 80% for more than 60 sec)
Time Frame: Through study completion, an average of 8 weeks
Toatal number of episodes of prolonged hypoxemia through the respiratory support
Through study completion, an average of 8 weeks
Brochopulmonary Dysplasia at 36 weeks PMA
Time Frame: Upto 36 weeks post menstrual age
Oxygen supplementation or need for respiratory support at 36 weeks PMA
Upto 36 weeks post menstrual age
Oxygen need at day 28
Time Frame: 4 weeks
Need for oxygen on day 28
4 weeks
Severe Retinopathy of Prematurity
Time Frame: Upto 36 weeks post menstrual age
Severe ROP requiring treatment
Upto 36 weeks post menstrual age
Periventricular Leuckomalacia
Time Frame: Upto 36 weeks post menstrual age
PVL diagnosed by Brain imaging through their stay in the NICU
Upto 36 weeks post menstrual age
Total number of days on supplemental oxygen less than 30%
Time Frame: Upto 36 weeks post menstrual age
The total number of days the infant has spent in the oxygen less than 30%
Upto 36 weeks post menstrual age
Length of hospital day
Time Frame: Upto 36 weeks post menstrual age
Total duration of stay in Neonatal Unit
Upto 36 weeks post menstrual age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

South Tees Hospitals NHS Foundation Trust

Collaborators

Vyaire Medical

Investigators

  • Principal Investigator: Vrinda Nair, MD,FRCPCH, South Tees NHS Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 1, 2020

Primary Completion (ACTUAL)

January 31, 2022

Study Completion (ACTUAL)

January 31, 2022

Study Registration Dates

First Submitted

January 3, 2020

First Submitted That Met QC Criteria

January 7, 2020

First Posted (ACTUAL)

January 10, 2020

Study Record Updates

Last Update Posted (ACTUAL)

July 15, 2022

Last Update Submitted That Met QC Criteria

July 14, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 277057

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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