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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Anemia of Prematurity

Intervention / Treatment
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* Other: red blood cell transfusion
* Other: red blood cell transfusion


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 3 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: liberal transfusion triggers<br>liberal guidelines for red blood cell transfusions | Other: red blood cell transfusion<br>* Implementation of liberal guidelines for red blood cell transfusions in extremely low birth weight infants<br>|
| Active Comparator: restrictive transfusion triggers<br>restrictive guidelines for red blood cell transfusions | Other: red blood cell transfusion<br>* Implementation of restrictive guidelines for red blood cell transfusions in extremely low birth weight infants<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prematurity, anemia, transfusion