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

• Sponsor: University Hospital Tuebingen
• Collaborator: German Research Foundation
• Information provided by (Responsible Party): Axel Franz, University Hospital Tuebingen

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Anemia of Prematurity	Other: red blood cell transfusion	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 920 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Transfusion Thresholds on Neurocognitive Outcome of Extremely Low Birth Weight Infants (ETTNO)- a Blinded Randomized Controlled Multicenter Trial
• Study Start Date: July 2011
• Actual Primary Completion Date: April 30, 2017
• Actual Study Completion Date: October 31, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: "liberal" transfusion triggers; "liberal" guidelines for red blood cell transfusions	Other: red blood cell transfusion; Implementation of "liberal" guidelines for red blood cell transfusions in extremely low birth weight infants
Active Comparator: "restrictive" transfusion triggers; "restrictive" guidelines for red blood cell transfusions	Other: red blood cell transfusion; Implementation of "restrictive" guidelines for red blood cell transfusions in extremely low birth weight infants

Outcome Measures

Primary Outcome Measures :

1. Incidence of death or major neurodevelopmental impairment [ Time Frame: 24 months of age corrected for prematurity ]
   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

Eligibility Criteria

• Ages Eligible for Study: up to 3 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Denmark

Neonatalklinikken

Copenhagen, Denmark, 2100

Germany

University Hospital of Aachen

Aachen, Germany, 52074

Children's Hospital

Augsburg, Germany, 86156

Vivantes Children's Hospital

Berlin, Germany, 12351

Charité University Children's Hospital

Berlin, Germany, 13353

University Children's Hospital

Bochum, Germany, 44791

Children's Hospital

Cologne, Germany, 50375

University Children's Hospital

Cologne, Germany, 50924

Children's Hospital

Datteln, Germany, 45711

University Children's Hospital

Dresden, Germany, 01307

University of Duesseldorf

Duesseldorf, Germany, 40225

Helios Children's Hospital

Erfurt, Germany, 99089

Children's Hospital

Erlangen, Germany, 91054

University Children's Hospital

Essen, Germany, 45122

University Children's Hospital

Frankfurt, Germany, 60590

University Children's Hospital

Giessen, Germany, 35385

University of Greifswald

Greifswald, Germany, 17475

Children's Hospital Eppendorf

Hamburg, Germany, 20246

Children's Hospital Altona

Hamburg, Germany, 22763

Children's Hospital

Hannover, Germany, 30625

University Hospital of Leipzig

Leipzig, Germany, 04103

University of Luebeck

Luebeck, Germany, 23538

University Children's Hospital

Magdeburg, Germany, 39120

University Hospital of Marburg

Marburg, Germany, 35033

University Children's Hospital

Muenster, Germany, 48149

University Children's Hospital

Munich, Germany, 80337

Children's Hospital

Nuremberg, Germany, 90471

Children's Hospital St. Hedwig

Regensburg, Germany, 93049

DRK Kinderklinik

Siegen, Germany, 57072

Children's Hospital

Stuttgart, Germany, 70176

University Hospital of Tuebingen

Tuebingen, Germany, 72076

University Children's Hospital

Ulm, Germany, 89075

Sponsors and Collaborators

University Hospital Tuebingen

German Research Foundation

Investigators

• Principal Investigator: Axel R Franz, MD; University Hospital of Tuebingen

More Information

Publications:

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.

• Responsible Party: Axel Franz, Coordinating Investigator, University Hospital Tuebingen
• ClinicalTrials.gov Identifier: NCT01393496 History of Changes
• Other Study ID Numbers: DFG Fr 1455/6-1; 2010-021576-28 ( EudraCT Number )
• First Posted: July 13, 2011
• Last Update Posted: December 21, 2018
• Last Verified: December 2018

Keywords provided by Axel Franz, University Hospital Tuebingen:

prematurity; anemia; transfusion

Additional relevant MeSH terms:

Premature Birth; Birth Weight; Body Weight; Signs and Symptoms; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications