Effects of Transfusion Thresholds on Neurocognitive Outcome of Extremely Low Birth Weight Infants

NCT ID: NCT01393496

Last Updated: 2021-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 1013 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2018-10-31

Brief Summary

To compare the effect of restrictive versus liberal red blood cell transfusion thresholds on long-term neurodevelopmental outcome in extremely low birth weight infants.

Detailed Description

Extremely low birth weight (ELBW) infants uniformly develop anemia of prematurity and frequently require multiple red blood cell transfusions (RBCT) during neonatal intensive care. The criteria currently applied to indicate RBCT in this population are based on expert opinion rather than evidence and conclusive data of long-term effects of RBCT practices do not exist. Both, giving RBCT to improve oxygen carrying capacity and restricting RBCT to avoid RBCT associated risks and costs potentially impair long-term development. The proposed blinded randomized controlled trial was designed and will be powered to compare the effect of restrictive versus liberal red blood cell transfusion guidelines on long-term neurodevelopmental outcome in ELBW infants. ELBW infants will be randomized to receive RBCT according to liberal or restrictive RBCT guidelines, which both reflect current practice in Germany and aim for a clinically relevant difference in mean hemoglobin concentrations. The primary outcome measure is the incidence of death or major neurodevelopmental impairment determined at 24 months of age corrected for prematurity. Key secondary outcomes are the incidences of individual components of the composite primary outcome, the mental and physical developmental index scores of the Bayley Scales of Infant Development (II edition), and growth. Safety analyses will assess the incidences of all major diseases of prematurity. The results of this trial may help to improve the quality of life of these patients and reduce long-term health care costs.

Conditions

Anemia of Prematurity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

"liberal" transfusion triggers

"liberal" guidelines for red blood cell transfusions

Group Type: EXPERIMENTAL

red blood cell transfusion

Intervention Type: OTHER

Implementation of "liberal" guidelines for red blood cell transfusions in extremely low birth weight infants

"restrictive" transfusion triggers

"restrictive" guidelines for red blood cell transfusions

Group Type: ACTIVE_COMPARATOR

red blood cell transfusion

Intervention Type: OTHER

Implementation of "restrictive" guidelines for red blood cell transfusions in extremely low birth weight infants

Interventions

red blood cell transfusion

Implementation of "liberal" guidelines for red blood cell transfusions in extremely low birth weight infants

Intervention Type: OTHER

red blood cell transfusion

Implementation of "restrictive" guidelines for red blood cell transfusions in extremely low birth weight infants

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Infants with a birth weight of 400 - 999g

Exclusion Criteria

• Missing written parental consent.
• Gestational age > 29 + 6/7 weeks
• Major congenital anomalies (including chromosomal aberrations, cyanotic congenital heart defects, syndromes likely affecting long-term outcome, and major congenital malformations requiring surgical correction during newborn period).
• Infants who died before 48 hours, infants in whom the clinical decision to withhold intensive care was made, infants who were not considered viable
• Participation in another study with ongoing use of an unlicensed investigational product from 28 days before study enrollment until the end of the study

• Minimum Eligible Age: 0 Days
• Maximum Eligible Age: 3 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German Research Foundation

OTHER

Sponsor Role: collaborator

University Hospital Tuebingen

OTHER

Sponsor Role: lead

Responsible Party

Axel Franz

Coordinating Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Axel R Franz, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Tuebingen

Locations

Neonatalklinikken

Copenhagen, , Denmark

University Hospital of Aachen

Aachen, , Germany

Children's Hospital

Augsburg, , Germany

Vivantes Children's Hospital

Berlin, , Germany

Charité University Children's Hospital

Berlin, , Germany

University Children's Hospital

Bochum, , Germany

Children's Hospital

Cologne, , Germany

University Children's Hospital

Cologne, , Germany

Children's Hospital

Datteln, , Germany

University Children's Hospital

Dresden, , Germany

University of Duesseldorf

Düsseldorf, , Germany

Helios Children's Hospital

Erfurt, , Germany

Children's Hospital

Erlangen, , Germany

University Children's Hospital

Essen, , Germany

University Children's Hospital

Frankfurt, , Germany

University Children's Hospital

Giessen, , Germany

University of Greifswald

Greifswald, , Germany

Children's Hospital Eppendorf

Hamburg, , Germany

Children's Hospital Altona

Hamburg, , Germany

Children's Hospital

Hanover, , Germany

University Hospital of Leipzig

Leipzig, , Germany

University of Luebeck

Lübeck, , Germany

University Children's Hospital

Magdeburg, , Germany

University Hospital of Marburg

Marburg, , Germany

University Children's Hospital

Munich, , Germany

University Children's Hospital

Münster, , Germany

Children's Hospital

Nuremberg, , Germany

Children's Hospital St. Hedwig

Regensburg, , Germany

DRK Kinderklinik

Siegen, , Germany

Children's Hospital

Stuttgart, , Germany

University Hospital of Tuebingen

Tübingen, , Germany

University Children's Hospital

Ulm, , Germany

Countries

Denmark; Germany

References

ETTNO Investigators. The 'Effects of Transfusion Thresholds on Neurocognitive Outcome of Extremely Low Birth-Weight Infants (ETTNO)' Study: Background, Aims, and Study Protocol. Neonatology. 2012 Jun;101(4):301-305. doi: 10.1159/000335030. Epub 2012 Jan 27.

Reference Type: BACKGROUND

PMID: 22298226 (View on PubMed)

Franz AR, Engel C, Bassler D, Rudiger M, Thome UH, Maier RF, Krageloh-Mann I, Kron M, Essers J, Buhrer C, Rellensmann G, Rossi R, Bittrich HJ, Roll C, Hohn T, Ehrhardt H, Avenarius S, Korner HT, Stein A, Buxmann H, Vochem M, Poets CF; ETTNO Investigators. Effects of Liberal vs Restrictive Transfusion Thresholds on Survival and Neurocognitive Outcomes in Extremely Low-Birth-Weight Infants: The ETTNO Randomized Clinical Trial. JAMA. 2020 Aug 11;324(6):560-570. doi: 10.1001/jama.2020.10690.

Reference Type: RESULT

PMID: 32780138 (View on PubMed)

Carson JL, Stanworth SJ, Dennis JA, Fergusson DA, Pagano MB, Roubinian NH, Turgeon AF, Valentine S, Trivella M, Doree C, Hebert PC. Transfusion thresholds and other strategies for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2025 Oct 20;10:CD002042. doi: 10.1002/14651858.CD002042.pub6.

Reference Type: DERIVED

PMID: 41114449 (View on PubMed)

Franz AR, Engel C, Bassler D, Rudiger M, Thome UH, Maier RF, Krageloh-Mann I, Essers J, Buhrer C, Bittrich HJ, Roll C, Hohn T, Ehrhardt H, Boettger R, Korner HT, Stein A, Neuberger P, Henriksen TB, Greisen G, Poets CF; ETTNO Investigators. Effects of liberal versus restrictive transfusion strategies on intermittent hypoxaemia in extremely low birthweight infants: secondary analyses of the ETTNO randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2025 Mar 26:fetalneonatal-2024-327643. doi: 10.1136/archdischild-2024-327643. Online ahead of print.

Reference Type: DERIVED

PMID: 40139741 (View on PubMed)

Radford M, Estcourt LJ, Sirotich E, Pitre T, Britto J, Watson M, Brunskill SJ, Fergusson DA, Doree C, Arnold DM. Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support. Cochrane Database Syst Rev. 2024 May 23;5(5):CD011305. doi: 10.1002/14651858.CD011305.pub3.

Reference Type: DERIVED

PMID: 38780066 (View on PubMed)

Carson JL, Stanworth SJ, Dennis JA, Trivella M, Roubinian N, Fergusson DA, Triulzi D, Doree C, Hebert PC. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2021 Dec 21;12(12):CD002042. doi: 10.1002/14651858.CD002042.pub5.

Reference Type: DERIVED

PMID: 34932836 (View on PubMed)

Other Identifiers

2010-021576-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DFG Fr 1455/6-1

Identifier Type: -

Identifier Source: org_study_id