Clinical trial NCT03163108: Closed-loop Automatic Oxygen Control (CLAC-4) in Preterm Infants
Official title: Closed-loop Automatic Oxygen Control (CLAC-4) in Preterm Infants: a Randomized Controlled Trial of a Revised Algorithm
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infant Respiratory Distress Syndrome
Ventilator Lung; Newborn
Keywords: controller
hyperoxia
hypoxia
ventilation
cerebral oxygenation
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
Collaborators: name: Johannes Gutenberg University Mainz
name: Heinen und Löwenstein GmbH & Co. KG
First posted: 2017-05-22
Enrollment: 19
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Two-center, randomised controlled, cross-over clinical trial in preterm infants born at gestational age below 34+1/7 weeks receiving supplemental oxygen and respiratory support (Continous positive airway pressure (CPAP) or Non-invasive Ventilation (NIV) or Invasive Ventilation (IV)). Routine manual control (RMC) of the fraction of inspired oxygen (FiO2) will be tested against RMC supported by closed-loop automatic control (CLAC) with "slow"-algorithm and RMC supported by CLAC with "fast"-algorithm.

The primary hypothesis is, that the use of the "faster" algorithm results in more time within arterial oxygen saturation (SpO2) target range compared to RMC only. The a-priori subordinate hypothesis is, that the faster algorithm is equally effective as the slower algorithm to maintain the SpO2 in the target range.

Detailed description: BACKGROUND AND OBJECTIVE In preterm infants receiving supplemental oxygen, routine manual control (RMC) of the fraction of inspired oxygen (FiO2) is often difficult and time consuming. The investigators developed a system for closed-loop automatic control (CLAC) of the FiO2 and demonstrated its safety and efficacy in a multi-center study. The objective of this study is to test a revised, "faster" algorithm with a shorter WAIT-interval of 30sec (= time between FiO2 changes) against the previously tested algorithm (WAIT of 180sec) and against RMC. The primary hypothesis is, that the application of CLAC with the "faster" algorithm in addition to RMC results in more time within arterial oxygen saturation (SpO2) target range compared to RMC only. The a-priori subordinate hypothesis is, that the faster algorithm is equally effective as the slower algorithm to maintain the SpO2 in the target range.

Further hypotheses for exploratory testing are, that the "fast" algorithm will achieve a higher proportion of time with SpO2 within target range and an improved stability of cerebral oxygenation (measured as rcStO2 and rcFtO2E determined by Near-infrared spectroscopy) compared with the slow algorithm.

STUDY DESIGN The Study is designed as a two-center, randomized controlled, cross-over clinical trial in preterm infants receiving mechanical ventilation or nasal continuous positive airway pressure or non-invasive ventilation and supplemental oxygen (FiO2 above 0.21). Within a twenty-four-hour period the investigators will compare 8 hours of RMC with 8-hour periods of RMC supported by CLAC "slow" algorithm or "fast" algorithm, respectively.

Eligibility criteria: Inclusion Criteria:

* gestational age at birth \<34+1/7weeks
* invasive mechanical ventilation OR noninvasive ventilation OR continous positive airway pressure support
* Fraction of inspired oxygen above 0.21 before inclusion
* more than 2 hypoxaemic events (arterial oxygen saturation below 80%) within 8 hours before inclusion
* parental written informed consent

Exclusion Criteria:

* congenital pulmonary anomalies
* diaphragmatic hernia or other diaphragmatic disorders

Primary outcomes:
measure: Proportion of time with SpO2 within target range
timeFrame: 16 hours
measure: Proportion of Time with SpO2 within target range
timeFrame: 16 hours
Secondary outcomes:
measure: Duration of hyperoxaemia
timeFrame: 16 hours
measure: Duration of hypoxaemia
timeFrame: 16 hours
measure: Duration of "overshoot" hyperoxaemia
timeFrame: 16 hours
measure: Number of "overshoot" hyperoxaemia
timeFrame: 16 hours
measure: Stability of cerebral oxygenation
timeFrame: 24 hours
Other outcomes:
measure: Staff workload
timeFrame: 24 hours
Locations:
city: Mainz
country: Germany
facility: Johannes Gutenberg University Mainz
city: Tubingen
country: Germany
facility: University of Tubingen
Study officials:
affiliation: University Hospital Tuebingen
name: Axel R Franz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schwarz CE, Kidszun A, Bieder NS, Franz AR, Konig J, Mildenberger E, Poets CF, Seyfang A, Urschitz MS. Is faster better? A randomised crossover study comparing algorithms for closed-loop automatic oxygen control. Arch Dis Child Fetal Neonatal Ed. 2020 Jul;105(4):369-374. doi: 10.1136/archdischild-2019-317029. Epub 2019 Sep 16.