Red Cell Transfusions for Premature Infants

(TOP Trial)

Recruiting at 19 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 3

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)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

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

1824 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment for premature infants?

Research shows that using more restrictive red blood cell transfusion guidelines can limit donor exposure and reduce costs without increasing negative health outcomes in extremely low birth-weight infants. Additionally, different transfusion volumes were studied, and both were found to affect oxygen levels in the brain and intestines of premature infants. ^{1 2 3 4 5}

Is red blood cell transfusion safe for premature infants?

Red blood cell transfusions in premature infants can have risks, including chronic lung disease, eye problems, brain bleeding, and gut issues. Studies suggest that using fewer transfusions might be safer than more frequent ones, but more research is needed to fully understand the risks. ^{5 6 7 8 9}

How does the treatment of liberal versus restricted red cell transfusion differ for premature infants?

The treatment of liberal versus restricted red cell transfusion for premature infants is unique because it involves different thresholds for when to give blood transfusions, which can affect the number of transfusions and potential complications. This approach is tailored to balance the need for oxygen delivery with the risk of transfusion-related complications, unlike standard practices that may not differentiate based on these thresholds. ^{2 10 11 12 13}

What is the purpose of this trial?

The objective of the TOP trial is to determine whether higher hemoglobin thresholds for transfusing ELBW infants resulting in higher hemoglobin levels lead to improvement in the primary outcome of survival and rates of neurodevelopmental impairment (NDI) at 22-26 months of age, using standardized assessments by Bayley.

Research Team

Abbot R Laptook, MD

Principal Investigator

Brown University, Women & Infants Hospital of Rhode Island

C. Michael Cotten, MD

Principal Investigator

Duke University

Krisa P Van Meurs, MD

Principal Investigator

Stanford University

Waldemar A Carlo, MD

Principal Investigator

University of Alabama at Birmingham

Kristi L Watterberg, MD

Principal Investigator

University of New Mexico

Myra Wyckoff, MD

Principal Investigator

University of Texas, Southwestern Medical Center at Dallas

Michele C Walsh, MD MS

Principal Investigator

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

Carl T D'Angio, MD

Principal Investigator

University of Rochester

Pablo Sanchez, MD

Principal Investigator

Research Institute at Nationwide Children's Hospital

Bradley Yoder, MD

Principal Investigator

University of Utah

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

Abhik Das, PhD

Principal Investigator

RTI International

Beena Sood, MD

Principal Investigator

Wayne State University

William Truog, MD

Principal Investigator

Children's Mercy Hospital Kansas City

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. China pubmed.ncbi.nlm.nih.gov

[Comparison of clinical outcomes in very low birth weight infants with anemia by different transfusion strategies]. [2010]

2. England pubmed.ncbi.nlm.nih.gov

Cerebral and intestinal oxygen saturation of different volumes of red blood cell transfusion in preterm infants. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Outcomes of a Quality Improvement Initiative to Prevent Unnecessary Packed Red Blood Cell Transfusions Among Extremely Low Birth-Weight Neonates. [2022]

4. France pubmed.ncbi.nlm.nih.gov

Comparison of restrictive and liberal red blood cell suspension transfusion and analysis of influencing factors on prognosis of premature infants. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Effects of transfusions in extremely low birth weight infants: a retrospective study. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Adverse effects of small-volume red blood cell transfusions in the neonatal population. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

New frontiers in neonatal red blood cell transfusion research. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Transfusion strategies in hematologic and nonhematologic disease. [2016]

9. United States pubmed.ncbi.nlm.nih.gov

Updates in Red Blood Cell and Platelet Transfusions in Preterm Neonates. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Factors associated with red blood cell transfusions in very-low-birth-weight preterm infants in Brazilian neonatal units. [2018]

11. Australia pubmed.ncbi.nlm.nih.gov

Restrictive versus liberal red blood cell transfusion thresholds in very low birth weight infants: a systematic review and meta-analysis. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Neonatal red blood cell transfusion. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

Association of red blood cell transfusion volume with postoperative complications and mortality in neonatal surgery. [2022]