Clinical trial NCT01393496: Effects of Transfusion Thresholds on Neurocognitive Outcome of Extremely Low Birth Weight Infants
Official title: Effects of Transfusion Thresholds on Neurocognitive Outcome of Extremely Low Birth Weight Infants (ETTNO)- a Blinded Randomized Controlled Multicenter Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Anemia of Prematurity
Keywords: prematurity
anemia
transfusion
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
Collaborators: name: German Research Foundation
First posted: 2011-07-13
Enrollment: 1013
Sex: ALL
Minimum age (years): 0
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of death or major neurodevelopmental impairment
timeFrame: 24 months of age corrected for prematurity
Secondary outcomes:
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Neonatalklinikken
city: Aachen
country: Germany
facility: University Hospital of Aachen
city: Augsburg
country: Germany
facility: Children's Hospital
city: Berlin
country: Germany
facility: Vivantes Children's Hospital
city: Berlin
country: Germany
facility: Charité University Children's Hospital
city: Bochum
country: Germany
facility: University Children's Hospital
city: Cologne
country: Germany
facility: Children's Hospital
city: Cologne
country: Germany
facility: University Children's Hospital
city: Datteln
country: Germany
facility: Children's Hospital
city: Dresden
country: Germany
facility: University Children's Hospital
city: Duesseldorf
country: Germany
facility: University of Duesseldorf
city: Erfurt
country: Germany
facility: Helios Children's Hospital
city: Erlangen
country: Germany
facility: Children's Hospital
city: Essen
country: Germany
facility: University Children's Hospital
city: Frankfurt
country: Germany
facility: University Children's Hospital
city: Giessen
country: Germany
facility: University Children's Hospital
city: Greifswald
country: Germany
facility: University of Greifswald
city: Hamburg
country: Germany
facility: Children's Hospital Eppendorf
city: Hamburg
country: Germany
facility: Children's Hospital Altona
city: Hannover
country: Germany
facility: Children's Hospital
city: Leipzig
country: Germany
facility: University Hospital of Leipzig
city: Luebeck
country: Germany
facility: University of Luebeck
city: Magdeburg
country: Germany
facility: University Children's Hospital
city: Marburg
country: Germany
facility: University Hospital of Marburg
city: Muenster
country: Germany
facility: University Children's Hospital
city: Munich
country: Germany
facility: University Children's Hospital
city: Nuremberg
country: Germany
facility: Children's Hospital
city: Regensburg
country: Germany
facility: Children's Hospital St. Hedwig
city: Siegen
country: Germany
facility: DRK Kinderklinik
city: Stuttgart
country: Germany
facility: Children's Hospital
city: Tuebingen
country: Germany
facility: University Hospital of Tuebingen
city: Ulm
country: Germany
facility: University Children's Hospital
Study officials:
affiliation: University Hospital of Tuebingen
name: Axel R Franz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.