Transfusion of Prematures Trial (TOP)

NICHD Neonatal Research Network

Status: Completed

Conditions: Anemia; Bronchopulmonary Dysplasia (BPD); Infant, Extremely Low Birth Weight; Infant, Small for Gestational Age; Infant, Newborn, Diseases

Treatments: Procedure: Restricted red cell transfusion; Procedure: Liberal Cell Transfusion

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT01702805

U01HL112776 (U.S. NIH Grant/Contract)

NICHD-NRN-0050

U01HL112748 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

Long-term outcomes of extremely low birth weight (ELBW) preterm infants, those weighing less than or equal to 1000 g at birth, are poor and pose a major health care burden. Virtually all of these infants are transfused, but at inconsistent hemoglobin (Hgb) thresholds.

The investigators propose in TOP to randomize infants less than or equal to 1000 g BW and gestational age at least 22 weeks but less than 29 weeks to receive red blood cell (RBC) transfusions according to one of two strategies of Hgb thresholds, either a high Hgb (liberal transfusion) or a low Hgb (restrictive transfusion) algorithm. It is currently unknown which transfusion strategy is superior. TOP is powered to demonstrate which strategy reduces the primary outcome of death or neurodisability in survivors at 22-26 months.

A secondary study entitled "Effect of Blood Transfusion Practices on Cerebral and Somatic Oximetry", also known as the NIRS study, will determine differences in cerebral oxygenation and fractional tissue oxygen extraction with NIRS between high and low hemoglobin threshold groups during red blood cell transfusions. The investigators also propose to determine whether abnormal cerebral NIRS measures are a better predictor of NDI than hemoglobin alone and whether abnormal mesenteric NIRS measures are associated with the development of NEC within the 48 hours following a transfusion.

A secondary study entitled "Economic Evaluation Ancillary to the Transfusion of Prematures Randomized Controlled Trial" will determine whether higher transfusion threshold will result in lower total costs to society over the first 22 to 26 corrected months of life and estimate the incremental cost-effectiveness ratio for survival without neurodevelopmental impairment, from the perspective of society, the third-party payer, and the family.

Extended follow-up: Subjects will be seen for a follow-up visit at 5-6 years corrected age to assess neurological and functional outcomes at early school age based on neonatal transfusion threshold.

Enrollment: 1,824 patients

Sex: All

Ages: Under 48 hours old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Birth weight less than or equal to 1000 grams.
• Gestational age at least 22 weeks but less than 29 weeks
• Admitted to the NICU within 48 hours of life

Exclusion criteria

• Considered nonviable by the attending neonatologist
• Cyanotic congenital heart disease
• Parents opposed to the transfusion of blood
• Parents with hemoglobinopathy or congenital anemia
• In-utero fetal transfusion
• Twin-to-twin transfusion syndrome
• Isoimmune hemolytic disease
• Lack of parental consent
• Severe acute hemorrhage, acute shock, sepsis with coagulopathy, or need for perioperative transfusion.
• Prior blood transfusion on clinical grounds beyond the first 6 hours of life
• Infant has received erythropoietin prior to randomization, or is intended to receive erythropoietin through the neonatal course
• Congenital condition, other than premature birth, that adversely affects life expectancy or neurodevelopment.
• High probability that the family is socially disorganized to the point of being unable to attend follow-up at 22-26 months.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,824 participants in 2 patient groups

Low Threshold Transfusion

Active Comparator group

Description:

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

Treatment:

Procedure: Restricted red cell transfusion

High Threshold Transfusion

Active Comparator group

Description:

Transfusions will be administered using a higher threshold hemoglobin value.

Treatment:

Procedure: Liberal Cell Transfusion