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

NCT03168516 | Active Not Recruiting Phase 3 DMC

• 3 other identifiers: FiO2-C2018-000453-41BMBF-Fz01KG1602
• Study Type: interventional
• Target: 1,065
• Locations: 4 countries
• Sites: 32

Brief Summary

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

Conditions

Infant,Premature

Keywords

Oxygen; closed-loop automatic control; Oxygen saturation; preterm infants

Outcome Measures

Primary Outcomes (2)

• Primary outcome I: composite outcome of death, severe retinopathy of prematurity (ROP), chronic lung disease of prematurity (BPD), necrotizing enterocolitis (NEC)

  The primary outcome I is a composite of any of the following: * Death * Severe retinopathy of prematurity (severe ROP, as defined in 7.3.1) * Chronic lung disease of prematurity (BPD, according to the physiological definition, which is described in detail in the study protocol) * Necrotizing enterocolitis (NEC, as defined in the study protocol) until discharge from hospital The primary endpoint I will be analysed between the two intervention groups using a stratified chi2-test and Cochrane Mantel-Haenszel statistics will be presented (risk ratios and 95%-confidence intervals). The factors considered for randomization (center, sex and gestational age at birth (\<26 weeks and ≥26 weeks) will also be used for analysis.

  until/at post-menstrual age (PMA) 36 weeks (death, BPD and NEC) and at latest at PMA 44 weeks for severity of ROP

• Primary outcome II: composite of death or neurodevelopmental impairment (NDI)

  The primary outcome II is a composite of any of the following: • death or neurodevelopmental impairment (defined as at least one of the following components: motor disability (GMFCS 2-5), language or cognitive delay (language composite score \< 85 or cognitive composite score \< 85 on Bayley Scales of Infant Development, 3rd edition) or severe visual or hearing impairment (need for a hearing aid or cochlear implant)). In case of missing Bayley III test results, Bayley II results, other developmental test results or PARCA-R parent questionnaire results may substitute for the Bayley III test results in a hierarchical manner described in the study protocol. The primary outcome II will be analysed between the two intervention groups using chi2-test and Cochrane Mantel-Haenszel statistics will be presented (risk ratios and 95%-confidence intervals). The factors considered for randomization (center, sex and gestational age at birth (\<26 weeks and ≥26 weeks) will also be used for analysis.

  at 24 months of age corrected for prematurity

Secondary Outcomes (16)

• Death

  24 months of age corrected for prematurity

• ROP Severity Score

  at latest at PMA 44 weeks

• Severe ROP

  at latest at PMA 44 weeks

• bronchopulmonary Dysplasia (BPD)

  until 36 weeks PMA

• Necrotizing enterocolitis (NEC)

  until 36 weeks PMA

Study Arms (2)

Experimental intervention

EXPERIMENTAL

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

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

Control intervention

NO INTERVENTION

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

Interventions

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

Experimental intervention

Eligibility Criteria

• Age: Up to 48 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (32)

Northwest Women's and Children's Hospital

Xi'an, 710061, China

Location

Klinikum St. Marien - Klinik für Kinder und Jugendliche

Amberg, 92224, Germany

Location

Josefinum - Klinik für Kinder und Jugendliche

Augsburg, 86154, Germany

Location

Diakonie Krankenhaus der Kreuznacher Diakonie

Bad Kreuznach, 55543, Germany

Location

Klinikum Links der Weser

Bremen, 29277, Germany

Location

Universitätsklinikum Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

HELIOS Klinikum Erfurt

Erfurt, 99089, Germany

Location

Klinikum Esslingen GmbH - Klinik für Kinder und Jugendliche

Esslingen am Neckar, 73730, Germany

Location

Zentrum für Kinder- und Jugendmedizin

Freiburg im Breisgau, 79106, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Städtisches Klinikum Karlsruhe

Karlsruhe, 76133, Germany

Location

University Hospital Leipzig

Leipzig, 04103, Germany

Location

Städtisches Klinikum - Klinik für Neonatologie

München, 80804, Germany

Location

München Klinik Harlaching

München, 81545, Germany

Location

Universitätsklinikum München

München - Großhadern, 81377, Germany

Location

Klinik für Kinder- und Jugendmedizin

Münster, 48149, Germany

Location

Klinik Hallerwiese - Cnopf'sche Kinderklinik

Nuremberg, 90419, Germany

Location

Krankenhaus Barmherzige Brüder

Regensburg, 93049, Germany

Location

Klinikum am Steinenberg

Reutlingen, 72764, Germany

Location

Leopoldina Krankenhaus der Stadt Schweinfurt GmbH

Schweinfurt, 97422, Germany

Location

Diakonissen-Stiftungs-Krankenhaus Speyer

Speyer, 67346, Germany

Location

Klinikum Stuttgart, Olgahospital

Stuttgart, 70174, Germany

Location

University Hospital Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, 89075, Germany

Location

Schwarzwald-Baar-Klinik

Villingen-Schwenningen, 78052, Germany

Location

Rems-Murr-Kliniken gGmbH

Winnenden, 71364, Germany

Location

Kindergeneeskunde Maastricht Universitair Medisch Centrum

Maastricht, 6229, Netherlands

Location

Máxima Medical Center

Veldhoven, 5504 DB, Netherlands

Location

Isala Kliniek Zwolle - Location Sophia

Zwolle, 8025, Netherlands

Location

The James Cook University Hospital

Middlesbrough, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 31630690 BACKGROUND

• 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.

  PMID: 39533330 DERIVED

Related Links

• study homepage

MeSH Terms

Conditions

Premature Birth

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Axel Franz, Prof. Dr.

  University Children's Hospital Tuebingen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2017
• First Posted: May 30, 2017
• Study Start: July 27, 2018
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 27, 2023

Record last verified: 2023-07

Locations

GB (1); NL (3); DE (27); CN (1)