Effects of Closed-loop Automatic Control of FiO2 in Extremely Preterm Infants

NCT ID: NCT03168516

Last Updated: 2023-12-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1065 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-27

Study Completion Date

2026-12-31

Brief Summary

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Extremely low gestational age neonates (ELGANs), i.e. those born at \<28 weeks, frequently experience intermittent hypoxemic/hyperoxemic episodes. Observational data indicate that severe and prolonged hypoxemic episodes are associated with retinopathy of prematurity (ROP), impaired long-term development and death. Closed-loop automated control of the inspiratory fraction of oxygen (FiO2-C) reduces time outside the oxygen target range, decreases number and duration of hypo- and hyperoxemic episodes, and reduces caregivers' workload. The proposed observer-blinded randomized controlled trial was designed and will be powered to compare the effect of FiO2-C in addition to manual adjustments, in comparison with manual adjustments of FiO2 only, on death and severe complications of prematurity thought to be related to hypoxia/hyperoxia and neurodevelopmental impairment in ELGANs. The results of this trial may help to improve the quality of life of ELGANs and reduce the burden of significant morbidity as well as costs for health care and society

Detailed Description

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Approximately 0.5% of all neonates (i.e., about 25,000 infants per year in Europe) are extremely low gestational age neonates (ELGANs), i.e. have a gestational age (GA) of \<28 completed weeks at birth. ELGANs have higher incidences of mortality, retinopathy of prematurity (ROP), chronic lung disease and other risks of prematurity as well as severe neurodevelopmental impairment.

The vast majority of ELGANs require supplemental oxygen in addition to mechanical respiratory support (including CPAP). Irrespective of the SpO2 target, the vast majority of ELGANs suffers from recurrent intermittent hypoxemic and (as a consequence of inappropriate adjustments of FiO2) hyperoxemic episodes. Recurrent intermittent hypoxic episodes - i.e. wide fluctuations in oxygen levels - are associated with an increased risk of ROP and there are data that suggest that late deaths and neurodevelopmental impairment are also linked to them.

Continuous positive airway pressure (CPAP) has been shown to reduce extubation failure in preterm infants, which may in part be due to a reduced frequency and severity of apnea of prematurity and stabilized functional residual capacity during apnea. Keeping oxygen levels (i.e., SpO2) stable despite irregular breathing patterns in ELGANs, requires frequent adjustments of the FiO2 which is both challenging, time consuming, and often impossible due to limited personnel resources.

FiO2-Controllers have been developed by several manufacturers of infant ventilators. They reduce the burden of hyper-/hypoxemia in infants while being safe and accurate in very short-term studies. The effects of FiO2-C on clinically relevant outcome measures and the safety of long-term continuous application, however, have yet to be elucidated. Hence there is now a window of opportunity to assess this new technology for benefits and harms, before it is implemented into neonatal care without appropriate evaluation of its safety and efficacy.

Conditions

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Infant,Premature

Keywords

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Oxygen closed-loop automatic control Oxygen saturation preterm infants

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Experimental intervention

closed-loop automatic control of the inspiratory fraction of oxygen (FiO2-C)

Group Type EXPERIMENTAL

closed-loop automatic control of the inspiratory fraction of oxygen (FiO2-C)

Intervention Type DEVICE

Application of FiO2-C (provided by standard infant ventilators) in addition to manual adjustments of the inspired oxygen fraction (FiO2) during mechanical ventilation and continuous positive airway pressure (CPAP) in ELGANs at least up to 32weeks PMA according to a standardized protocol

Control intervention

Standard care, i.e. manual adjustments of the FiO2 only

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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closed-loop automatic control of the inspiratory fraction of oxygen (FiO2-C)

Application of FiO2-C (provided by standard infant ventilators) in addition to manual adjustments of the inspired oxygen fraction (FiO2) during mechanical ventilation and continuous positive airway pressure (CPAP) in ELGANs at least up to 32weeks PMA according to a standardized protocol

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Preterm infants with a gestational age (GA) at birth of 23+0/7 - 27+6/7 weeks

Exclusion Criteria

* Decision for palliative care
* congenital anomalies
* postnatal age \> 48h
* missing parental consent
* lack of device enabling closed-loop automatic control of FiO2
Maximum Eligible Age

48 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital Tuebingen

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Axel Franz, Prof. Dr.

Role: STUDY_DIRECTOR

University Children's Hospital Tuebingen

Locations

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Northwest Women's and Children's Hospital

Xi'an, , China

Site Status

Klinikum St. Marien - Klinik für Kinder und Jugendliche

Amberg, , Germany

Site Status

Josefinum - Klinik für Kinder und Jugendliche

Augsburg, , Germany

Site Status

Diakonie Krankenhaus der Kreuznacher Diakonie

Bad Kreuznach, , Germany

Site Status

Klinikum Links der Weser

Bremen, , Germany

Site Status

Universitätsklinikum Dresden

Dresden, , Germany

Site Status

Universitätsklinikum Düsseldorf

Düsseldorf, , Germany

Site Status

HELIOS Klinikum Erfurt

Erfurt, , Germany

Site Status

Klinikum Esslingen GmbH - Klinik für Kinder und Jugendliche

Esslingen am Neckar, , Germany

Site Status

Zentrum für Kinder- und Jugendmedizin

Freiburg im Breisgau, , Germany

Site Status

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Site Status

Städtisches Klinikum Karlsruhe

Karlsruhe, , Germany

Site Status

University Hospital Leipzig

Leipzig, , Germany

Site Status

Städtisches Klinikum - Klinik für Neonatologie

München, , Germany

Site Status

München Klinik Harlaching

München, , Germany

Site Status

Universitätsklinikum München

München - Großhadern, , Germany

Site Status

Klinik für Kinder- und Jugendmedizin

Münster, , Germany

Site Status

Klinik Hallerwiese - Cnopf'sche Kinderklinik

Nuremberg, , Germany

Site Status

Krankenhaus Barmherzige Brüder

Regensburg, , Germany

Site Status

Klinikum am Steinenberg

Reutlingen, , Germany

Site Status

Leopoldina Krankenhaus der Stadt Schweinfurt GmbH

Schweinfurt, , Germany

Site Status

Diakonissen-Stiftungs-Krankenhaus Speyer

Speyer, , Germany

Site Status

Klinikum Stuttgart, Olgahospital

Stuttgart, , Germany

Site Status

University Hospital Tübingen

Tübingen, , Germany

Site Status

Universitätsklinikum Ulm

Ulm, , Germany

Site Status

Schwarzwald-Baar-Klinik

Villingen-Schwenningen, , Germany

Site Status

Rems-Murr-Kliniken gGmbH

Winnenden, , Germany

Site Status

Kindergeneeskunde Maastricht Universitair Medisch Centrum

Maastricht, , Netherlands

Site Status

Máxima Medical Center

Veldhoven, , Netherlands

Site Status

Isala Kliniek Zwolle - Location Sophia

Zwolle, , Netherlands

Site Status

The James Cook University Hospital

Middlesbrough, , United Kingdom

Site Status

Countries

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China Germany Netherlands United Kingdom

References

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Maiwald CA, Niemarkt HJ, Poets CF, Urschitz MS, Konig J, Hummler H, Bassler D, Engel C, Franz AR; FiO2-C Study Group. Effects of closed-loop automatic control of the inspiratory fraction of oxygen (FiO2-C) on outcome of extremely preterm infants - study protocol of a randomized controlled parallel group multicenter trial for safety and efficacy. BMC Pediatr. 2019 Oct 21;19(1):363. doi: 10.1186/s12887-019-1735-9.

Reference Type BACKGROUND
PMID: 31630690 (View on PubMed)

Konig J, Stauch A, Engel C, Urschitz MS, Franz AR; FiO2-C study group. Statistical analysis plan for the FiO2-C trial: effects of closed-loop automatic control of the inspiratory fraction of oxygen (FiO2-C) on outcomes of extremely preterm infants-a randomized-controlled parallel group multicentre trial for safety and efficacy. Trials. 2024 Nov 12;25(1):756. doi: 10.1186/s13063-024-08615-7.

Reference Type DERIVED
PMID: 39533330 (View on PubMed)

Related Links

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Other Identifiers

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2018-000453-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BMBF-Fz01KG1602

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

FiO2-C

Identifier Type: -

Identifier Source: org_study_id