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

Anemia of Prematurity Clinical Trial

— ETTNO  

Official title:

Effects of Transfusion Thresholds on Neurocognitive Outcome of Extremely Low Birth Weight Infants (ETTNO)- a Blinded Randomized Controlled Multicenter Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01393496
• Other study ID #: DFG Fr 1455/6-1
• Secondary ID: 2010-021576-28
• Status: Completed
• Phase: Phase 4
• Start date: July 2011
• Est. completion date: October 31, 2018

Study information

• Verified date: September 2021
• Source: University Hospital Tuebingen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1013
• Est. completion date: October 31, 2018
• Est. primary completion date: April 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 3 Days

Eligibility

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

Related Conditions & MeSH terms

• Anemia of Prematurity
• Birth Weight
• Premature Birth

Intervention

Other:
• red blood cell transfusion
Implementation of "liberal" guidelines for red blood cell transfusions in extremely low birth weight infants
• red blood cell transfusion
Implementation of "restrictive" guidelines for red blood cell transfusions in extremely low birth weight infants

Locations

Country	Name	City	State
Denmark	Neonatalklinikken	Copenhagen
Germany	University Hospital of Aachen	Aachen
Germany	Children's Hospital	Augsburg
Germany	Charité University Children's Hospital	Berlin
Germany	Vivantes 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	Duesseldorf
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 Altona	Hamburg
Germany	Children's Hospital Eppendorf	Hamburg
Germany	Children's Hospital	Hannover
Germany	University Hospital of Leipzig	Leipzig
Germany	University of Luebeck	Luebeck
Germany	University Children's Hospital	Magdeburg
Germany	University Hospital of Marburg	Marburg
Germany	University Children's Hospital	Muenster
Germany	University Children's Hospital	Munich
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	Tuebingen
Germany	University Children's Hospital	Ulm

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Tuebingen	German Research Foundation

Countries where clinical trial is conducted

Denmark,  Germany, 

References & Publications (2)

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. Epub 2012 Jan 27. — View Citation

Franz AR, Engel C, Bassler D, Rüdiger M, Thome UH, Maier RF, Krägeloh-Mann I, Kron M, Essers J, Bührer C, Rellensmann G, Rossi R, Bittrich HJ, Roll C, Höhn T, Ehrhardt H, Avenarius S, Körner HT, Stein A, Buxmann H, Vochem M, Poets CF; ETTNO Investigators. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of death or major neurodevelopmental impairment	The primary outcome measure of this study will be the incidence of death or major neurodevelopmental impairment determined at 24 months of age corrected for prematurity (where major neurodevelopmental impairment is defined as any of the following: cognitive delay defined as mental developmental index (MDI) score of the Bayley Scales of Infant Development (2nd edition) < 85, cerebral palsy, or severe visual or hearing impairment	24 months of age corrected for prematurity