AzTrials
AzTrials

Anemia of PrematurityPhase 4ETTNONCT01393496

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

A Phase 4 study testing red blood cell transfusion in people with Anemia of Prematurity, run by University Hospital Tuebingen at 32 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 0 to 3 days
Conditions the study is for
Anemia of Prematurity
What is being tested?
red blood cell transfusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,013 participants
Where
32 sitesin 2 countries
Study dates
Jul 2011to 31 Oct 2018
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 0 to 3 days
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Infants with a birth weight of 400 - 999g

Who cannot join

  • 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

Trial locations and contacts

32 sites in 2 countries.

32 sites in 2 countries

Germany31 sites

  • University Hospital of Aachen

    Aachen, 52074

  • Children's Hospital

    Augsburg, 86156

  • Vivantes Children's Hospital

    Berlin, 12351

  • Charité University Children's Hospital

    Berlin, 13353

  • University Children's Hospital

    Bochum, 44791

  • Children's Hospital

    Cologne, 50375

  • University Children's Hospital

    Cologne, 50924

  • Children's Hospital

    Datteln, 45711

  • University Children's Hospital

    Dresden, 01307

  • University of Duesseldorf

    Düsseldorf, 40225

  • Helios Children's Hospital

    Erfurt, 99089

  • Children's Hospital

    Erlangen, 91054

  • University Children's Hospital

    Essen, 45122

  • University Children's Hospital

    Frankfurt, 60590

  • University Children's Hospital

    Giessen, 35385

  • University of Greifswald

    Greifswald, 17475

  • Children's Hospital Eppendorf

    Hamburg, 20246

  • Children's Hospital Altona

    Hamburg, 22763

  • Children's Hospital

    Hanover, 30625

  • University Hospital of Leipzig

    Leipzig, 04103

  • University of Luebeck

    Lübeck, 23538

  • University Children's Hospital

    Magdeburg, 39120

  • University Hospital of Marburg

    Marburg, 35033

  • University Children's Hospital

    Munich, 80337

  • University Children's Hospital

    Münster, 48149

  • Children's Hospital

    Nuremberg, 90471

  • Children's Hospital St. Hedwig

    Regensburg, 93049

  • DRK Kinderklinik

    Siegen, 57072

  • Children's Hospital

    Stuttgart, 70176

  • University Hospital of Tuebingen

    Tübingen, 72076

  • University Children's Hospital

    Ulm, 89075

Other trials in Germany

Denmark1 site

  • Neonatalklinikken

    Copenhagen, 2100

Other trials in Denmark

About this study

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

To compare the effect of restrictive versus liberal red blood cell transfusion thresholds on long-term neurodevelopmental outcome in extremely low birth weight infants.

Read the 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.

Being tested
red blood cell transfusion
Keywords
prematurity, anemia, transfusion
Medical subject headings
Anemia, Premature Birth

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • red blood cell transfusionOther

    Implementation of "liberal" guidelines for red blood cell transfusions in extremely low birth weight infants

  • red blood cell transfusionOther

    Implementation of "restrictive" guidelines for red blood cell transfusions in extremely low birth weight infants

Study groups in NCT01393496
Study groupRoleWhat they receive
"liberal" transfusion triggersExperimental"liberal" guidelines for red blood cell transfusions
Receives: Other: red blood cell transfusion
"restrictive" transfusion triggersActive comparator"restrictive" guidelines for red blood cell transfusions
Receives: Other: red blood cell transfusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 24 months of age corrected for prematurity

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2011 (estimated)
  2. Study startJul 2011
  3. Primary completion30 Apr 2017
  4. Study completion31 Oct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
1,013 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01393496
Sponsor's protocol ID
DFG Fr 1455/6-1
Other IDs
2010-021576-28
Acronym
ETTNO
Status last verified
Sep 2021
First submitted
12 Jul 2011
Last updated
16 Sep 2021
Results posted
No
Data monitoring committee
Yes

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. doi: 10.1159/000335030. Epub 2012 Jan 27.

    PubMed 22298226

  • 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.

    PubMed 32780138

  • Carson JL, Stanworth SJ, Dennis JA, Fergusson DA, Pagano MB, Roubinian NH, Turgeon AF, Valentine S, Trivella M, Doree C, Hebert PC. Transfusion thresholds and other strategies for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2025 Oct 20;10(10):CD002042. doi: 10.1002/14651858.CD002042.pub6.

    PubMed 41114449

  • Franz AR, Engel C, Bassler D, Rudiger M, Thome UH, Maier RF, Krageloh-Mann I, Essers J, Buhrer C, Bittrich HJ, Roll C, Hohn T, Ehrhardt H, Boettger R, Korner HT, Stein A, Neuberger P, Henriksen TB, Greisen G, Poets CF; ETTNO Investigators. Effects of liberal versus restrictive transfusion strategies on intermittent hypoxaemia in extremely low birthweight infants: secondary analyses of the ETTNO randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2025 Oct 17;110(6):564-570. doi: 10.1136/archdischild-2024-327643.

    PubMed 40139741

  • Radford M, Estcourt LJ, Sirotich E, Pitre T, Britto J, Watson M, Brunskill SJ, Fergusson DA, Doree C, Arnold DM. Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support. Cochrane Database Syst Rev. 2024 May 23;5(5):CD011305. doi: 10.1002/14651858.CD011305.pub3.

    PubMed 38780066

  • 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.

    PubMed 34932836

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing red blood cell transfusion in people with Anemia of Prematurity, run by University Hospital Tuebingen at 32 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in Germany, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of death or major neurodevelopmental impairment (time frame: 24 months of age corrected for prematurity). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01393496, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in