Closed-loop Automatic Oxygen Control (CLAC-4) in Preterm Infants

Not Applicable

Completed

• Conditions: Infant Respiratory Distress Syndrome; Ventilator Lung; Newborn
• Interventions: Device: Closed-loop automatic oxygen control (CLAC) fast in addition to RMC; Device: Closed-loop automatic oxygen control (CLAC) slow in addition to RMC

• Registration Number: NCT03163108
• Lead Sponsor: University Hospital Tuebingen

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.

Study Timeline

• Status Verified: 2017-01
• Study Start: 2017-03-15
• Study First Submitted: 2017-03-30
• Study First Submitted QC: 2017-05-19
• Study First Posted: 2017-05-22
• Primary Completion: 2017-12-18
• Study Completion: 2018-01-12
• Last Update Submitted: 2018-05-09
• Last Update Posted: 2018-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
CLAC fast	Closed-loop automatic oxygen control (CLAC) fast in addition to RMC	routine manual control (RMC) + Closed-loop automatic oxygen control (CLAC) with 30sec WAIT-Interval ("fast" algorithm) of the fraction of inspired oxygen (FIO2)
CLAC slow	Closed-loop automatic oxygen control (CLAC) slow in addition to RMC	routine manual control (RMC) + Closed-loop automatic oxygen control (CLAC) with 180sec WAIT-Interval ("slow" algorithm) of the fraction of inspired oxygen (FIO2)

Primary Outcome Measures

Name	Time	Method
Proportion of time with SpO2 within target range	16 hours	Comparison of proportion of time with SpO2 within target range if the infant requires supplemental oxygen and time above target range if the infant requires no supplemental oxygen between CLAC-fast and RMC (superiority hypothesis).
Proportion of Time with SpO2 within target range	16 hours	Comparison of proportion of time with SpO2 within target range if the infant requires supplemental oxygen and time above target range if the infant requires no supplemental oxygen between CLAC-fast and CLAC-slow (subordinate, non inferiority hypothesis).

Secondary Outcome Measures

Name	Time	Method
Duration of hyperoxaemia	16 hours	Time with arterial oxygen saturation above 95% if the infant requires supplemental oxygen (hyperoxaemia).
Duration of hypoxaemia	16 hours	Time with arterial oxygen saturation below 80% (hypoxaemia)
Stability of cerebral oxygenation	24 hours	"Area under the curve" of cerebral tissue saturation or fraction of tissue oxygen extraction outside of the infants Median +- 5% or outside of the "save" interval of 55-80% rcStO2.
Duration of "overshoot" hyperoxaemia	16 hours	Comparison of proportion of time with SpO2 higher than 95% after an automated increase of FiO2 between CLAC-fast and CLAC-slow.
Number of "overshoot" hyperoxaemia	16 hours	Comparison of number of events with SpO2 higher than 95% after an automated increase of FiO2 between CLAC-fast and CLAC-slow.

Trial Locations

Locations (2)

Johannes Gutenberg University Mainz; 🇩🇪 Mainz, Germany

University of Tubingen; 🇩🇪 Tubingen, Germany