Phase 2 N=104 Basic Science

Red Blood Cell (RBC) Survival Following Transfusion in Infants

Neonatal Anemia

Bottom Line

View on ClinicalTrials.gov: NCT00731588 ↗

Enrolled (actual)

104

Serious AEs

0.0%

Results posted

Aug 2021

Primary outcome: Primary: Number of Discrete Biotinylated RBC Densities (up to 5 Discrete Densities) That Can be Accurately Measured by Flow Cytometry, i.e., Without Overlap. — 5; 5 flow cytometry RBC discrete peaks

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Transfused Biotin RBCs - Adults Phase I (Biological); Transfused Biotin RBCs - Infants Phase II (Biological); Transfused Biotin RBCs - Infants Phase III (Biological)
Age: Pediatric · 0+ yrs
Sex: All
Sponsor: John A Widness
Primary completion: Mar 2017

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Discrete Biotinylated RBC Densities (up to 5 Discrete Densities) That Can be Accurately Measured by Flow Cytometry, i.e., Without Overlap.	5; 5	—
PRIMARY RBC Survival (Life Span) in Days of Multiple, Distinct BioRBC Density Populations of Transfused Autologous RBCs in Adults and Premature Infants.	NA; 60; 120; 60; 120; 60	—
PRIMARY RBC Survival (Life Span) in Days of Multiple, Distinct BioRBC Density Populations of Transfused Allogeneic RBCs in Premature Infants.	60; 60; 60; 60	—
SECONDARY Number of Participants With Positive Antibody Screen in Response to Biotin-labeled RBCs.	3; 0	—
SECONDARY Survival of Allogeneic RBCs in Days as Measured by the Antigenic Method Using Flow Cytometry for Comparison With BioRBC in Premature Infants	70	—

Summary

OUR OVERALL HYPOTHESIS is that post-transfusion survival of allogeneic and autologous RBCs can be accurately quantified in anemic human infants using biotin-labeled RBCs combined with mathematical modeling that adjusts for confounding factors commonly encountered in neonates. These confounding factors include 1) dilution of labeled RBC as a result of growth stimulated erythropoiesis, anemia stimulated erythropoiesis, and blood transfusion; 2) loss of labeled RBC due to laboratory phlebotomy; and 3) variable RBC life spans resulting from RBCs having been produced at different developmental periods and under varying rates of erythropoiesis. In contrast to infants, adjustment for these factors is not necessary in healthy adults under conditions of steady state erythropoiesis. Instead in adults, RBC survival is typified by a linear decline in concentration of labeled RBCs over time. When this line is extrapolated to zero concentration, the intercept with the time axis represents the mean potential lifespan (MPL) of RBCs. ( 21 d) allogeneic adult RBCs transfused in the same infant.

Eligibility Criteria

Adult Study:

Inclusion Criteria

Males or post-menopausal females
18-65 years of age.
Weight >110 lbs.
Healthy- the subject feels well and can perform normal activities.
Hemoglobin at or above 12.5 g/dL or hematocrit at or above 38%.
Note: Members of the research team that are not supervised or under the employee of the PI may participate in the study.

Exclusion Criteria

Presence of chronic illness unless the subject is being treated and the condition is under control.
Consumption of biotin supplements or raw eggs.
Premenopausal women.
Blood donation in the previous 8 weeks (single donation) or 16 weeks (double red cell donation).
Blood loss in the previous 8 weeks due to epistaxis, gastrointestinal blood loss, trauma, significant diagnostic phlebotomy loss (i.e., > 30 mL total), or other significant bleeding
Treatment with antibiotics within the last 7 days. Antibiotics for prevention of an infection or treatment of acne are not exclusion criteria.
Note: If study subjects experience any of these conditions associated with blood loss or donate any blood products, they will not be included in the primary analysis but will be replaced.

Infant Study:

MOTHERS FOR PLACENTAL BLOOD COLLECTION AND MOTHERS OF INFANT STUDY SUBJECTS

Inclusion Criteria

>/= 24 weeks gestation
mothers who deliver through the birth canal or by c-section can be included in the study.

Exclusion Criteria

Pregnant with fetus with major congenital anomaly.
Clinically suspected or documented maternal chorioamnionitis (This only applies to infant study subjects receiving autologous RBCs from the placenta).
Viral or bacterial infection (e.g. HIV, Hepatitis B, Hepatitis C, Primary Herpes, Tuberculosis) based on clinically available prenatal or postnatal test results in the mother's medical record. (This only applies to infant study subjects receiving autologous RBCs from the placenta.)
minor mothers ( /=24 weeks gestation who are patients in the Neonatal Intensive Care Unit (NICU) at UIHC that:
Are being treated with the expectation of survival.

Exclusion Criteria

Difference of more than 5% in the percentage of HbF cells (measured by flow cytometry in the Widness lab) between blood harvested from the placenta and that from discarded neonatal blood in the first day of life and before the first neonatal blood transfusion. This is done to exclude the rare possibility of transfusing newborns with blood that is contaminated with a significant proportion of their mother's blood if a maternal-to-placenta bleed occurs after umbilical cord clamping is done. (This only applies to infant study subjects receiving autologous RBCs from the placenta.)
Need of emergent blood transfusion as determined by the subject's medical care team.
Hematological diseases (except for anemia associated with phlebotomy loss and prematurity)
Alloimmune hemolytic anemia, diffuse intravascular coagulation, and thrombosis.
Major congenital anomaly.
Sepsis with positive blood or spinal fluid culture.
Receiving treatment with erythropoietin (r-HuEPO) or cardiorespiratory bypass support (ECMO).
Overt clinical bleeding.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00731588). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.