Closed-loop Automatic Oxygen Control (CLAC-4) in Preterm Infants (CLAC-4)
Primary Purpose
Infant Respiratory Distress Syndrome, Ventilator Lung; Newborn
Status
Completed
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Closed-loop automatic oxygen control (CLAC) fast in addition to RMC
Closed-loop automatic oxygen control (CLAC) slow in addition to RMC
Sponsored by
About this trial
This is an interventional treatment trial for Infant Respiratory Distress Syndrome focused on measuring controller, hyperoxia, hypoxia, ventilation, cerebral oxygenation
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
Sites / Locations
- Johannes Gutenberg University Mainz
- University of Tubingen
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
No Intervention
Active Comparator
Experimental
Arm Label
RMC only
CLAC slow
CLAC fast
Arm Description
routine manual control (RMC) of the fraction of inspired oxygen (FIO2)
routine manual control (RMC) + Closed-loop automatic oxygen control (CLAC) with 180sec WAIT-Interval ("slow" algorithm) of the fraction of inspired oxygen (FIO2)
routine manual control (RMC) + Closed-loop automatic oxygen control (CLAC) with 30sec WAIT-Interval ("fast" algorithm) of the fraction of inspired oxygen (FIO2)
Outcomes
Primary Outcome Measures
Proportion of time with SpO2 within target range
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
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
Duration of hyperoxaemia
Time with arterial oxygen saturation above 95% if the infant requires supplemental oxygen (hyperoxaemia).
Duration of hypoxaemia
Time with arterial oxygen saturation below 80% (hypoxaemia)
Duration of "overshoot" hyperoxaemia
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
Comparison of number of events with SpO2 higher than 95% after an automated increase of FiO2 between CLAC-fast and CLAC-slow.
Stability of cerebral oxygenation
"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.
Full Information
NCT ID
NCT03163108
First Posted
March 30, 2017
Last Updated
May 9, 2018
Sponsor
University Hospital Tuebingen
Collaborators
Johannes Gutenberg University Mainz, Heinen und Löwenstein GmbH & Co. KG
1. Study Identification
Unique Protocol Identification Number
NCT03163108
Brief Title
Closed-loop Automatic Oxygen Control (CLAC-4) in Preterm Infants
Acronym
CLAC-4
Official Title
Closed-loop Automatic Oxygen Control (CLAC-4) in Preterm Infants: a Randomized Controlled Trial of a Revised Algorithm
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
March 15, 2017 (Actual)
Primary Completion Date
December 18, 2017 (Actual)
Study Completion Date
January 12, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Tuebingen
Collaborators
Johannes Gutenberg University Mainz, Heinen und Löwenstein GmbH & Co. KG
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infant Respiratory Distress Syndrome, Ventilator Lung; Newborn
Keywords
controller, hyperoxia, hypoxia, ventilation, cerebral oxygenation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RMC only
Arm Type
No Intervention
Arm Description
routine manual control (RMC) of the fraction of inspired oxygen (FIO2)
Arm Title
CLAC slow
Arm Type
Active Comparator
Arm Description
routine manual control (RMC) + Closed-loop automatic oxygen control (CLAC) with 180sec WAIT-Interval ("slow" algorithm) of the fraction of inspired oxygen (FIO2)
Arm Title
CLAC fast
Arm Type
Experimental
Arm Description
routine manual control (RMC) + Closed-loop automatic oxygen control (CLAC) with 30sec WAIT-Interval ("fast" algorithm) of the fraction of inspired oxygen (FIO2)
Intervention Type
Device
Intervention Name(s)
Closed-loop automatic oxygen control (CLAC) fast in addition to RMC
Intervention Description
Closed-loop automatic oxygen control is an automated, algorithm based adjustment of the fraction of inspired oxygen in relation to arterial saturation (WAIT-interval 30s).
Intervention Type
Device
Intervention Name(s)
Closed-loop automatic oxygen control (CLAC) slow in addition to RMC
Intervention Description
Closed-loop automatic oxygen control is an automated, algorithm based adjustment of the fraction of inspired oxygen in relation to arterial saturation (WAIT-interval 180s).
Primary Outcome Measure Information:
Title
Proportion of time with SpO2 within target range
Description
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).
Time Frame
16 hours
Title
Proportion of Time with SpO2 within target range
Description
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).
Time Frame
16 hours
Secondary Outcome Measure Information:
Title
Duration of hyperoxaemia
Description
Time with arterial oxygen saturation above 95% if the infant requires supplemental oxygen (hyperoxaemia).
Time Frame
16 hours
Title
Duration of hypoxaemia
Description
Time with arterial oxygen saturation below 80% (hypoxaemia)
Time Frame
16 hours
Title
Duration of "overshoot" hyperoxaemia
Description
Comparison of proportion of time with SpO2 higher than 95% after an automated increase of FiO2 between CLAC-fast and CLAC-slow.
Time Frame
16 hours
Title
Number of "overshoot" hyperoxaemia
Description
Comparison of number of events with SpO2 higher than 95% after an automated increase of FiO2 between CLAC-fast and CLAC-slow.
Time Frame
16 hours
Title
Stability of cerebral oxygenation
Description
"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.
Time Frame
24 hours
Other Pre-specified Outcome Measures:
Title
Staff workload
Description
number of manual adjustments of inspired oxygen per time
Time Frame
24 hours
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Axel R Franz, MD
Organizational Affiliation
University Hospital Tuebingen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johannes Gutenberg University Mainz
City
Mainz
Country
Germany
Facility Name
University of Tubingen
City
Tubingen
ZIP/Postal Code
72076
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Sharing individual participant data is not intended
Citations:
PubMed Identifier
31527093
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.
Results Reference
derived
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Closed-loop Automatic Oxygen Control (CLAC-4) in Preterm Infants
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