Red Blood Cell (RBC) Survival Following Transfusion in Infants

NCT00731588 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2007107472P01HL046925
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 2

Brief 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. (\<7 d) and stored (\>21 d) allogeneic adult RBCs transfused in the same infant.

Conditions

Neonatal Anemia

Outcome Measures

Primary Outcomes (3)

• Number of Discrete Biotinylated RBC Densities (up to 5 Discrete Densities) That Can be Accurately Measured by Flow Cytometry, i.e., Without Overlap.

  The biotin-labeled RBCs that were studied were: 2, 6, 18, 54, and 162 µg NHS-biotinylating reagent per mL of packed RBCs. Here we report the number of discrete biotin densities without overlap as determined in vitro.

  from day of blood draw this can be accomplished in 4 hours

• RBC Survival (Life Span) in Days of Multiple, Distinct BioRBC Density Populations of Transfused Autologous RBCs in Adults and Premature Infants.

  Using flow cytometry was measured for each RBC biotin density in days as determined when RBC measurement was no longer detectable.

  for up to 5 months

• RBC Survival (Life Span) in Days of Multiple, Distinct BioRBC Density Populations of Transfused Allogeneic RBCs in Premature Infants.

  Using flow cytometry was measured for each RBC biotin density in days as determined when RBC measurement was no longer detectable.

  for up to 4 months

Secondary Outcomes (2)

• Number of Participants With Positive Antibody Screen in Response to Biotin-labeled RBCs.

  4 to 5 mo post transfusion of biotin RBCs

• Survival of Allogeneic RBCs in Days as Measured by the Antigenic Method Using Flow Cytometry for Comparison With BioRBC in Premature Infants

  4 months

Study Arms (2)

PPG1A - Adults

EXPERIMENTAL

Phase I completed: Healthy male and post-menopausal female volunteers between the ages of 18 and 65. Volunteers must not have donated blood in the previous 8 weeks.

Biological: Transfused Biotin RBCs - Adults Phase I

PPG1B - Infants

EXPERIMENTAL

Phase II in progress: Newborns \>= 24 weeks gestation who are patients in the Neonatal Intensive Care Unit at the University of Iowa Hospitals and Clinics that are being treated with the expectation of survival.

Biological: Transfused Biotin RBCs - Infants Phase II; Biological: Transfused Biotin RBCs - Infants Phase III

Interventions

Transfused Biotin RBCs - Adults Phase I BIOLOGICAL

A 3 mL venous blood sample is obtained. 250 mL of blood will be drawn to a blood collection bag containing the anticoagulant CPD. Separate equal volumes of RBCs are labeled with up to five different densities of biotin. The biotinylated RBCs are resuspended in autologous plasma to achieve a 60 to 70% hematocrit. An IV is inserted for the reinfusion of the biotinylated RBCs. Three mL aliquots of blood are sampled at 5, 10, 20, and 60 minutes after infusion. The subject returns \~24 hours and 3 days after the RBC infusion to obtain a 3 mL venous blood sample. Subjects return for weekly 3 mL blood sampling.

PPG1A - Adults

Transfused Biotin RBCs - Infants Phase II BIOLOGICAL

After the infant's clinical care team decides that a RBC transfusion is needed, a 15mL/kilogram of body weight is ordered. Transfusion will be given in 2 parts: 1) approximately 80% of the total transfusion to be transfused over 3-4 hours and 2) approximately 20% of the total transfusion will be marked with biotin to be transfused upon completion of the first part. The bedside nurse maintains constant observation of the infant as appropriate for the infant's condition, assessing for signs and symptoms of a transfusion reaction.

PPG1B - Infants

Transfused Biotin RBCs - Infants Phase III BIOLOGICAL

Phase III (infants) to be determined upon completion of Phase II (infants).

PPG1B - Infants

Eligibility Criteria

• Age: 1 Hour - 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Males or post-menopausal females
• 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.

You may not qualify if:

• 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
• 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
• \>/= 24 weeks gestation
• mothers who deliver through the birth canal or by c-section can be included in the study.
• 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 (\<18 years old) are excluded from the study.
• INFANT STUDY SUBJECTS

Sponsors & Collaborators

• John A Widness: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Thrasher Research Fund: collaborator

Study Sites (2)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Related Publications (10)

• Mock DM, Matthews NI, Strauss RG, Burmeister LF, Schmidt R, Widness JA. Red blood cell volume can be independently determined in vitro using sheep and human red blood cells labeled at different densities of biotin. Transfusion. 2009 Jun;49(6):1178-85. doi: 10.1111/j.1537-2995.2009.02095.x. Epub 2009 Feb 10.

  PMID: 19220818 RESULT

• Mock DM, Matthews NI, Zhu S, Burmeister LF, Zimmerman MB, Strauss RG, Schmidt RL, Nalbant D, Cress GA, Widness JA. Red blood cell (RBC) volume can be independently determined in vivo in humans using RBCs labeled at different densities of biotin. Transfusion. 2011 Jan;51(1):148-57. doi: 10.1111/j.1537-2995.2010.02770.x.

  PMID: 20630041 RESULT

• Mock DM, Matthews NI, Zhu S, Strauss RG, Schmidt RL, Nalbant D, Cress GA, Widness JA. Red blood cell (RBC) survival determined in humans using RBCs labeled at multiple biotin densities. Transfusion. 2011 May;51(5):1047-57. doi: 10.1111/j.1537-2995.2010.02926.x. Epub 2010 Nov 9.

  PMID: 21062290 RESULT

• Mock DM, Lankford GL, Matthews NI, Burmeister LF, Kahn D, Widness JA, Strauss RG. Accelerated removal of antibody-coated red blood cells from the circulation is accurately tracked by a biotin label. Transfusion. 2012 May;52(5):1097-105. doi: 10.1111/j.1537-2995.2011.03397.x. Epub 2011 Oct 24.

  PMID: 22023312 RESULT

• Mock DM, Widness JA, Strauss RG, Franco RS. Posttransfusion red blood cell (RBC) survival determined using biotin-labeled RBCs has distinct advantages over labeling with (51) Cr. Transfusion. 2012 Jul;52(7):1596-8. doi: 10.1111/j.1537-2995.2012.03588.x. No abstract available.

  PMID: 22780899 RESULT

• Nalbant D, Bhandary P, Matthews NI, Schmidt RL, Bogusiewicz A, Cress GA, Zimmerman MB, Strauss RG, Mock DM, Widness JA. Comparison of multiple red cell volume methods performed concurrently in premature infants following allogeneic transfusion. Pediatr Res. 2013 Nov;74(5):592-600. doi: 10.1038/pr.2013.143. Epub 2013 Sep 3.

  PMID: 24088873 RESULT

• Widness JA, Nalbant D, Matthews NI, Strauss RG, Schmidt RL, Cress GA, Zimmerman MB, Mock DM. Tracking donor RBC survival in premature infants: agreement of multiple populations of biotin-labeled RBCs with Kidd antigen-mismatched RBCs. Pediatr Res. 2013 Dec;74(6):689-97. doi: 10.1038/pr.2013.163. Epub 2013 Sep 4.

  PMID: 24108188 RESULT

• Widness JA, Kuruvilla DJ, Mock DM, Matthews NI, Nalbant D, Cress GA, Schmidt RL, Strauss RG, Zimmerman MB, Veng-Pedersen P. Autologous Infant and Allogeneic Adult Red Cells Demonstrate Similar Concurrent Post-Transfusion Survival in Very Low Birth Weight Neonates. J Pediatr. 2015 Nov;167(5):1001-6. doi: 10.1016/j.jpeds.2015.08.028. Epub 2015 Sep 9.

  PMID: 26363547 RESULT

• Schmidt RL, Mock DM, Franco RS, Cohen RM, North AK, Cancelas JA, Geisen C, Strauss RG, Vlaar AP, Nalbant D, Widness JA. Antibodies to biotinylated red blood cells in adults and infants: improved detection, partial characterization, and dependence on red blood cell-biotin dose. Transfusion. 2017 Jun;57(6):1488-1496. doi: 10.1111/trf.14075. Epub 2017 Mar 5.

  PMID: 28261808 RESULT

• Nalbant D, Cancelas JA, Mock DM, Kyosseva SV, Schmidt RL, Cress GA, Zimmerman MB, Strauss RG, Widness JA. In premature infants there is no decrease in 24-hour posttransfusion allogeneic red blood cell recovery after 42 days of storage. Transfusion. 2018 Feb;58(2):352-358. doi: 10.1111/trf.14396. Epub 2017 Nov 29.

  PMID: 29193118 DERIVED

MeSH Terms

Conditions

Anemia, Neonatal

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: John A. Widness, M.D.
• Organization: University of Iowa

john-widness@uiowa.edu

319-356-8102

Study Officials

• John A Widness, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 5, 2008
• First Posted: August 11, 2008
• Study Start: June 1, 2008
• Primary Completion: March 1, 2017
• Study Completion: March 2, 2018
• Last Updated: August 13, 2021
• Results First Posted: August 13, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)