Infant Respiratory Distress SyndromeCLAC-4NCT03163108
Closed-loop Automatic Oxygen Control (CLAC-4) in Preterm Infants
A study of Infant Respiratory Distress Syndrome and Ventilator Lung; Newborn, run by University Hospital Tuebingen at 2 sites in Germany.
Trial 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)). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Infant Respiratory Distress Syndrome, Ventilator Lung; Newborn
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 2 sitesGermany
- Study dates
- 15 Mar 2017to 12 Jan 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- congenital pulmonary anomalies
- diaphragmatic hernia or other diaphragmatic disorders
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
Johannes Gutenberg University Mainz
Mainz
University of Tubingen
Tübingen, 72076
About this study
Official title: Closed-loop Automatic Oxygen Control (CLAC-4) in Preterm Infants: a Randomized Controlled Trial of a Revised Algorithm
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.
Read the 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.
- Being tested
- Closed-loop automatic oxygen control (CLAC) fast in addition to RMC, Closed-loop automatic oxygen control (CLAC) slow in addition to RMC
- Keywords
- controller, hyperoxia, hypoxia, ventilation, cerebral oxygenation
- Medical subject headings
- Pulmonary Atelectasis, Bronchopulmonary Dysplasia, Hyperoxia, Hypoxia, Respiratory Aspiration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Closed-loop automatic oxygen control (CLAC) fast in addition to RMCDevice
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).
Closed-loop automatic oxygen control (CLAC) slow in addition to RMCDevice
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).
| Study group | Role | What they receive |
|---|---|---|
| RMC only | No intervention | routine manual control (RMC) of the fraction of inspired oxygen (FIO2) |
| CLAC slow | Active comparator | routine manual control (RMC) + Closed-loop automatic oxygen control (CLAC) with 180sec WAIT-Interval ("slow" algorithm) of the fraction of inspired oxygen (FIO2) Receives: Device: Closed-loop automatic oxygen control (CLAC) slow in addition to RMC |
| CLAC fast | Experimental | routine manual control (RMC) + Closed-loop automatic oxygen control (CLAC) with 30sec WAIT-Interval ("fast" algorithm) of the fraction of inspired oxygen (FIO2) Receives: Device: Closed-loop automatic oxygen control (CLAC) fast in addition to RMC |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 16 hours
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).
Measured: 16 hours
Secondary outcomes (5)
Duration of hyperoxaemia
Time with arterial oxygen saturation above 95% if the infant requires supplemental oxygen (hyperoxaemia).
Measured: 16 hours
Duration of hypoxaemia
Time with arterial oxygen saturation below 80% (hypoxaemia)
Measured: 16 hours
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.
Measured: 16 hours
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.
Measured: 16 hours
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.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2017
- Study start15 Mar 2017
- Primary completion18 Dec 2017
- Study completion12 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Infant Respiratory Distress SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Collaborators
- Johannes Gutenberg University Mainz, Heinen und Löwenstein GmbH & Co. KG
- Responsible party
- Sponsor
- Investigators
- Axel R Franz, MD, Principal investigator, University Hospital Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03163108
- Sponsor's protocol ID
- CLAC-4
- Acronym
- CLAC-4
- Status last verified
- Jan 2017
- First submitted
- 30 Mar 2017
- Last updated
- 15 May 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Sharing individual participant data is not intended
Publications
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.
PubMed 31527093
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Closed-loop Automatic Oxygen Control (CLAC-4) in Preterm Infants: a Randomized Controlled Trial of a Revised Algorithm
- ClinicalTrials.gov ID
- NCT03163108
- Acronym / sponsor ID
- CLAC-4 / CLAC-4
- Keywords
- controller, hyperoxia, hypoxia, ventilation, cerebral oxygenation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Collaborators
- Johannes Gutenberg University Mainz, Heinen und Löwenstein GmbH & Co. KG
- Study start
- 15 Mar 2017 (actual)
- Primary completion
- 18 Dec 2017 (actual)
- Study completion
- 12 Jan 2018 (actual)
- First posted
- 22 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| RMC only | No intervention | –routine manual control (RMC) of the fraction of inspired oxygen (FIO2) |
| CLAC slow | Active comparator | Device: Closed-loop automatic oxygen control (CLAC) slow in addition to RMCroutine manual control (RMC) + Closed-loop automatic oxygen control (CLAC) with 180sec WAIT-Interval ("slow" algorithm) of the fraction of inspired oxygen (FIO2) |
| CLAC fast | Experimental | Device: Closed-loop automatic oxygen control (CLAC) fast in addition to RMCroutine manual control (RMC) + Closed-loop automatic oxygen control (CLAC) with 30sec WAIT-Interval ("fast" algorithm) of the fraction of inspired oxygen (FIO2) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (2 listed)
- congenital pulmonary anomalies
- diaphragmatic hernia or other diaphragmatic disorders
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Closed-loop automatic oxygen control (CLAC) fast in addition to RMCClosed-loop automatic oxygen control is an automated, algorithm based adjustment of the fraction of inspired oxygen in relation to arterial saturation (WAIT-interval 30s). | Device | CLAC fast |
| Closed-loop automatic oxygen control (CLAC) slow in addition to RMCClosed-loop automatic oxygen control is an automated, algorithm based adjustment of the fraction of inspired oxygen in relation to arterial saturation (WAIT-interval 180s). | Device | CLAC slow |
Primary outcome
Proportion of time with SpO2 within target range
Time frame: 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
Time frame: 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).
5 secondary outcomes
Duration of hyperoxaemia
Time frame: 16 hours
Duration of hypoxaemia
Time frame: 16 hours
Duration of "overshoot" hyperoxaemia
Time frame: 16 hours
Number of "overshoot" hyperoxaemia
Time frame: 16 hours
Stability of cerebral oxygenation
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2018.
- Derived from this study: PubMed 31527093Schwarz 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.
- Individual participant dataSharing planned: No. Sharing individual participant data is not intended
Related trials for Infant Respiratory Distress Syndrome
Not yet recruiting
The Hemodynamic Impact of High-frequency Oscillatory Ventilation and Periodic Sighs in Preterm Infants
Preterm, Respiratory Distress Syndrome in Premature Infant
Active, not recruiting
Measuring Diaphragm Electrical Activity in Neonates Using a Smaller Inter-electrode Distance
Respiratory Distress Syndrome, Newborn, Infant, Premature
RecruitingPhase 3
Safety and Efficacy of APC-0101 in Preterm Infants With Respiratory Distress Syndrome
Respiratory Distress Syndrome, Pre-term Infants
Active, not recruiting
30% or 60% Oxygen at Birth to Improve Neurodevelopmental Outcomes in Very Low Birthweight Infants
Premature Infant, Respiratory Distress Syndrome in Premature Infant
Recruiting
Optimising Breathing Support at Extubation in Very Preterm Infants: A Clinical Study
Respiratory Distress Syndrome, Newborn, Respiratory Distress Syndrome in Premature Infant
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Axel R Franz, MD principal investigator
University Hospital Tuebingen
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Infant Respiratory Distress Syndrome and Ventilator Lung; Newborn, run by University Hospital Tuebingen at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of time with SpO2 within target range (time frame: 16 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03163108, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2018; AzTrials last refreshed its copy on 30 Oct 2026.