Red Blood Cell (RBC) Survival Following Transfusion in Infants - Full Text View

Purpose

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.

Condition	Intervention	Phase
Neonatal Anemia	Biological: Transfused Biotin RBCs - Adults Phase I Biological: Transfused Biotin RBCs - Infants Phase II Biological: Transfused Biotin RBCs - Infants Phase III	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	Red Blood Cell Survival Following Transfusion in Infants

Resource links provided by NLM:

MedlinePlus related topics: Anemia Blood Transfusion and Donation

Drug Information available for: Biotin

U.S. FDA Resources

Further study details as provided by University of Iowa:

Primary Outcome Measures:

To develop in vitro and validate in vivo in adults the capability for biotinylating RBCs at up to 5 discrete densities that are measurable by flow cytometry. [ Time Frame: 5 min - 6 mo post transfusion of biotin RBC's ] [ Designated as safety issue: No ]
Simultaneously determine RBC survival of multiple, distinct populations of transfused RBCs in premature infants. RBC survival results will be compared with those of the differential agglutination, antigenic method. [ Time Frame: 20 minutes - 2 months ] [ Designated as safety issue: No ]
To compare long-term survival results for transfused adult donor and fetal/placental RBCs in anemic newborn infants. [ Time Frame: 20 min - 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess if antibodies to biotin-labeled RBCs may develop and to assess if the biotinylated RBCs may be removed ot destroyed by the subject's circulatory system. [ Time Frame: 5 min - 6 mo post transfusion of biotin RBCs ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	80
Study Start Date:	June 2008
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	February 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: PPG1A - Adults 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 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.
Experimental: PPG1B - Infants 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 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. Biological: Transfused Biotin RBCs - Infants Phase III Phase III (infants) to be determined upon completion of Phase II (infants).

Arms

Assigned Interventions

Experimental: PPG1A - Adults

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

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.

Experimental: PPG1B - Infants

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

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.

Biological: Transfused Biotin RBCs - Infants Phase III

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

Show Detailed Description

Eligibility

Ages Eligible for Study:	up to 6 Months
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 birthcanal 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 (<18 years old) are excluded from the study.

INFANT STUDY SUBJECTS

Inclusion Criteria:

Newborns >/=24 weeks gestation who are patients in the Neonatal Intensive Care Unit (NICU) at UIHC that:

1) 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00731588

Contacts

Contact: Gretchen Cress

319-356-2151

gretchen-cress@uiowa.edu

Locations

United States, Iowa
University of Iowa	Recruiting
Iowa City, Iowa, United States, 52242
University of Iowa Hospitals and Clinics	Recruiting
Iowa City, Iowa, United States, 52242

Sponsors and Collaborators

University of Iowa

National Institutes of Health (NIH)

National Heart, Lung, and Blood Institute (NHLBI)

Thrasher Research Fund

Investigators

Principal Investigator:

John A Widness, MD

University of Iowa

More Information

No publications provided

Responsible Party:	University of Iowa
ClinicalTrials.gov Identifier:	NCT00731588 History of Changes
Other Study ID Numbers:	200710747, 2P01HL046925
Study First Received:	August 5, 2008
Last Updated:	December 6, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Anemia
Anemia, Neonatal
Hematologic Diseases
Infant, Newborn, Diseases
Biotin
Vitamin B Complex

Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 17, 2013