Red Cell Transfusions for Premature Infants

(TOP Trial)

No longer recruiting at 19 trial locations

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: NICHD Neonatal Research Network

Must not be taking: Erythropoietin

Disqualifiers: Congenital heart disease, Anemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 weeks postmenstrual age or initial hospital discharge

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best method for administering blood transfusions to extremely low birth weight (ELBW) premature infants. Researchers aim to determine if maintaining higher hemoglobin levels (the protein in red blood cells that carries oxygen) enhances survival and brain development compared to usual care. The trial includes two groups: one receives liberal red cell transfusions at higher hemoglobin levels, while the other follows standard practice with restricted red cell transfusions at lower levels. Newborns weighing 1000 grams or less and admitted to the NICU within their first two days are suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to potentially life-saving advancements in neonatal care.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both flexible and strict approaches to red blood cell transfusions are generally safe for anemic preterm infants. A review of 12 studies found these methods effective and safe. Other studies found no major differences in survival rates or brain development when using higher or lower hemoglobin levels to guide transfusions. This indicates both methods are well-tolerated. However, debate continues about the optimal level for preterm babies. Overall, evidence indicates that the treatments under study are safe for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores how different thresholds for red cell transfusions could improve care for premature infants. Unlike the standard practice of using a lower hemoglobin threshold for transfusions, the trial also examines a higher threshold to see if it offers better outcomes for these vulnerable patients. The hope is that by comparing these two approaches, researchers can better understand which method leads to healthier development and fewer complications in premature infants. This could potentially redefine best practices for blood transfusions in neonatal care.

What evidence suggests that this trial's treatments could be effective for premature infants?

This trial will compare two transfusion strategies for premature infants: High Threshold Transfusion and Low Threshold Transfusion. Research has shown that giving more blood transfusions to premature babies does not improve their chances of surviving without brain development issues by age 2. Studies have found that both more and fewer transfusions are generally safe and effective for anemic preterm babies. However, current guidelines often recommend fewer transfusions, as this might benefit babies born early. Blood transfusions are linked to long-term brain development, affecting how the brain grows over time. Therefore, selecting the right transfusion plan is crucial for the health and development of premature infants. ^{1 2 3 6 7}

Who Is on the Research Team?

Bradley Yoder, MD

Principal Investigator

University of Utah

Carl T D'Angio, MD

Principal Investigator

University of Rochester

Michele C Walsh, MD MS

Principal Investigator

Case Western Reserve University, Rainbow Babies and Children's Hospital

Waldemar A Carlo, MD

Principal Investigator

University of Alabama at Birmingham

Myra Wyckoff, MD

Principal Investigator

University of Texas, Southwestern Medical Center at Dallas

Abbot R Laptook, MD

Principal Investigator

Brown University, Women & Infants Hospital of Rhode Island

Krisa P Van Meurs, MD

Principal Investigator

Stanford University

Pablo Sanchez, MD

Principal Investigator

Research Institute at Nationwide Children's Hospital

C. Michael Cotten, MD

Principal Investigator

Duke University

Kristi L Watterberg, MD

Principal Investigator

University of New Mexico

Ravi Patel, MD

Principal Investigator

Emory University

Uday Devaskar, MD

Principal Investigator

University of California, Los Angeles

Haresh M Kirpalani, MD

Principal Investigator

University of Pennsylvania

William Truog, MD

Principal Investigator

Children's Mercy Hospital Kansas City

Abhik Das, PhD

Principal Investigator

RTI International

Beena Sood, MD

Principal Investigator

Wayne State University

Kathleen A Kennedy, MD MPH

Principal Investigator

The University of Texas Health Science Center, Houston

Brenda Poindexter, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Greg Sokol, MD

Principal Investigator

Indiana University

Are You a Good Fit for This Trial?

The TOP trial is for extremely low birth weight infants with a gestational age of 22-28 weeks, admitted to the NICU within 48 hours of life, and weighing less than or equal to 1000 grams. Infants who've had prior transfusions (beyond first 6 hours), received erythropoietin, have congenital conditions affecting survival/neurodevelopment, severe acute conditions, or whose parents cannot attend follow-up are excluded.

Inclusion Criteria

Gestational age at least 22 weeks but less than 29 weeks

Admitted to the NICU within 48 hours of life

Birth weight less than or equal to 1000 grams.

Exclusion Criteria

Infant has received erythropoietin prior to randomization, or is intended to receive erythropoietin through the neonatal course

You have had a blood transfusion while still in your mother's womb.

Lack of parental consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Infants are randomized to receive red blood cell transfusions according to either a high or low hemoglobin threshold strategy

Up to 36 weeks postmenstrual age or initial hospital discharge

Follow-up

Participants are monitored for survival and neurodevelopmental impairment at 22-26 months corrected age

22-26 months

Extended Follow-up

Subjects will be seen for a follow-up visit at 5-6 years corrected age to assess neurological and functional outcomes

5-6 years corrected age

What Are the Treatments Tested in This Trial?

Interventions

• Liberal Cell Transfusion
• Restricted red cell transfusion

Trial Overview This study tests if higher hemoglobin thresholds in red cell transfusions for very small premature babies can improve survival and neurodevelopment at around two years old. Babies will be randomly assigned to receive either more frequent 'liberal' or less frequent 'restricted' blood transfusions.

How Is the Trial Designed?

Group I: High Threshold Transfusion Active Control 1 Intervention

Transfusions will be administered using a higher threshold hemoglobin value.

Group II: Low Threshold Transfusion Active Control 1 Intervention

Transfusions will be administered using a lower threshold hemoglobin value. The low threshold values reflect more common practice, so this is considered the 'usual treatment' group

Who Is Running the Clinical Trial?

NICHD Neonatal Research Network

Lead Sponsor

Trials

62

Recruited

209,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

This systematic review aims to clarify the incidence and types of adverse effects associated with small-volume red blood cell (RBC) transfusions (10-20 mL/kg) in neonates, addressing a significant gap in current research.

RBC transfusions in neonates are linked to serious morbidities such as chronic lung disease and retinopathy of prematurity, highlighting the need for a better understanding of the risks versus benefits in transfusion practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of small-volume red blood cell transfusions in the neonatal population. Keir, A., Pal, S., Trivella, M., et al.[2021]

A review of over 7000 patients in clinical trials indicates that a restrictive transfusion strategy (7-8 g/dL) is generally safe and may be superior to a liberal strategy (9-10 g/dL) for most patients.

However, for patients with specific conditions like myocardial infarction or stroke, more research is needed, as preliminary evidence suggests that a liberal transfusion strategy could be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transfusion strategies in hematologic and nonhematologic disease. Carson, JL., Strair, R.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9889497/

a meta-analysis of 12 randomized controlled trials - PMC Overall, both liberal and restrictive transfusion thresholds are effective and safer strategies to red blood cell transfusion in anemic preterm ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2820028

Clinical Practice Guideline for Red Blood Cell Transfusion ... This consensus statement recommends a restrictive RBC transfusion strategy, with moderate certainty of evidence, for preterm neonates with less than 30 weeks' ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2020248

Higher or Lower Hemoglobin Transfusion Thresholds for ... A higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for ...

4. publications.aap.org publications.aap.org/pediatrics/article/154/2/e2023063728/197791/Decreasing-Blood-Transfusions-in-Premature-Infants

Decreasing Blood Transfusions in Premature Infants ... pRBCT can be decreased in preterm infants born between 26 and 34 completed weeks' gestation through a combination of strategies utilizing quality improvement ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8796841/

Red blood cell transfusions in preterm newborns and ... In preterm infants, RBC transfusions are associated with long-term neurodevelopmental outcome, with a cumulative effect.

6. frontiersin.org frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.957585/full

Thresholds for blood transfusion in extremely preterm infants There are two recently completed large randomized clinical trials of blood transfusions in the preterm infants most at risk of requiring them.

7. bmcpediatr.biomedcentral.com bmcpediatr.biomedcentral.com/articles/10.1186/s12887-025-05732-3

The transfusion of prematures early school age follow-up ... There is conflicting evidence regarding which hemoglobin thresholds for red blood cell transfusion should be used for the preterm population.