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

Prematurity Clinical Trial

— AreOS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04223258
• Other study ID #: 277057
• Status: Completed
• Phase: N/A
• Start date: October 1, 2020
• Est. completion date: January 31, 2022

Study information

• Verified date: July 2022
• Source: South Tees Hospitals NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: January 31, 2022
• Est. primary completion date: January 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 23 Weeks to 32 Weeks

Eligibility

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

Related Conditions & MeSH terms

• Premature Birth
• Prematurity

Intervention

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.

Other:
• Manual Oxygen Control
In the manual arm the oxygen is adjusted manually by the clinical team.

Locations

Country	Name	City	State
United Kingdom	South Tees NHS Trust	Middlesbrough

Sponsors (2)

Lead Sponsor	Collaborator
South Tees Hospitals NHS Foundation Trust	Vyaire Medical

Country where clinical trial is conducted

United Kingdom, 

References & Publications (7)

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. — View Citation

Laptook AR, Salhab W, Allen J, Saha S, Walsh M. Pulse oximetry in very low birth weight infants: can oxygen saturation be maintained in the desired range? J Perinatol. 2006 Jun;26(6):337-41. — View Citation

Martin RJ, Wang K, Köroglu O, Di Fiore J, Kc P. Intermittent hypoxic episodes in preterm infants: do they matter? Neonatology. 2011;100(3):303-10. doi: 10.1159/000329922. Epub 2011 Oct 3. Review. — View Citation

Poets CF, Roberts RS, Schmidt B, Whyte RK, Asztalos EV, Bader D, Bairam A, Moddemann D, Peliowski A, Rabi Y, Solimano A, Nelson H; Canadian Oxygen Trial Investigators. Association Between Intermittent Hypoxemia or Bradycardia and Late Death or Disability in Extremely Preterm Infants. JAMA. 2015 Aug 11;314(6):595-603. doi: 10.1001/jama.2015.8841. — View Citation

Stenson B, Brocklehurst P, Tarnow-Mordi W; U.K. BOOST II trial; Australian BOOST II trial; New Zealand BOOST II trial. Increased 36-week survival with high oxygen saturation target in extremely preterm infants. N Engl J Med. 2011 Apr 28;364(17):1680-2. doi: 10.1056/NEJMc1101319. — View Citation

Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, Hale EC, Newman NS, Schibler K, Carlo WA, Kennedy KA, Poindexter BB, Finer NN, Ehrenkranz RA, Duara S, Sánchez PJ, O'Shea TM, Goldberg RN, Van Meurs KP, Faix RG, Phelps DL, Frantz ID 3rd, Watterberg KL, Saha S, Das A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics. 2010 Sep;126(3):443-56. doi: 10.1542/peds.2009-2959. Epub 2010 Aug 23. — View Citation

SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network, Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG, Laptook AR, Yoder BA, Faix RG, Das A, Poole WK, Schibler K, Newman NS, Ambalavanan N, Frantz ID 3rd, Piazza AJ, Sánchez PJ, Morris BH, Laroia N, Phelps DL, Poindexter BB, Cotten CM, Van Meurs KP, Duara S, Narendran V, Sood BG, O'Shea TM, Bell EF, Ehrenkranz RA, Watterberg KL, Higgins RD. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med. 2010 May 27;362(21):1959-69. doi: 10.1056/NEJMoa0911781. Epub 2010 May 16. — View Citation

Outcome

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