Effects of Transfusion Thresholds on Neurocognitive Outcome of Extremely Low Birth Weight Infants (ETTNO)- a Blinded Randomized Controlled Multicenter Trial
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Enrollment
- 1,013
- Locations
- 32
- Primary Endpoint
- Incidence of death or major neurodevelopmental impairment
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 0 Days to 3 Days (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
"liberal" transfusion triggers
"liberal" guidelines for red blood cell transfusions
Intervention: red blood cell transfusion (Other)
"restrictive" transfusion triggers
"restrictive" guidelines for red blood cell transfusions
Intervention: red blood cell transfusion (Other)
Outcomes
Primary Outcomes
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
Secondary Outcomes
No secondary outcomes reported
Investigators
Axel Franz
Coordinating Investigator
University Hospital Tuebingen