Trial Outcomes & Findings for Red Blood Cell (RBC) Survival Following Transfusion in Infants (NCT NCT00731588)

Last Updated: 2021-08-13

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

140 participants

Primary outcome timeframe

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

Results posted on

2021-08-13

Participant Flow

Some infants (actually the mothers were asked for consent for their infants) were enrolled before birth and then after birth were found to be ineligible. No cord blood was available in some cases and thus could not be studied.

Participant milestones

Participant milestones
Measure	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. 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.	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. 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. Transfused Biotin RBCs - Infants Phase III: Phase III (infants) to be determined upon completion of Phase II (infants).
Overall Study STARTED	9	95
Overall Study COMPLETED	9	53
Overall Study NOT COMPLETED	0	42

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Red Blood Cell (RBC) Survival Following Transfusion in Infants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PPG1A - Adults n=9 Participants 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. 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.	PPG1B - Infants n=53 Participants 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. 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. Transfused Biotin RBCs - Infants Phase III: Phase III (infants) to be determined upon completion of Phase II (infants).	Total n=62 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	53 Participants n=7 Participants	53 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	0 Participants n=7 Participants	9 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	32 Participants n=7 Participants	38 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	21 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	47 Participants n=7 Participants	56 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	9 Participants n=5 Participants	53 Participants n=7 Participants	62 Participants n=5 Participants

PRIMARY outcome

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

Population: These were representative samples studied in vitro from infants and adults

Outcome measures

Outcome measures
Measure	PPG1A - Adults n=3 Participants 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. 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.	PPG1B - Infants n=3 Participants 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. 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. Transfused Biotin RBCs - Infants Phase III: Phase III (infants) to be determined upon completion of Phase II (infants).
Number of Discrete Biotinylated RBC Densities (up to 5 Discrete Densities) That Can be Accurately Measured by Flow Cytometry, i.e., Without Overlap.	5 flow cytometry RBC discrete peaks	5 flow cytometry RBC discrete peaks

PRIMARY outcome

Timeframe: for up to 5 months

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

Outcome measures

Outcome measures
Measure	PPG1A - Adults n=9 Participants 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. 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.	PPG1B - Infants n=53 Participants 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. 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. Transfused Biotin RBCs - Infants Phase III: Phase III (infants) to be determined upon completion of Phase II (infants).
RBC Survival (Life Span) in Days of Multiple, Distinct BioRBC Density Populations of Transfused Autologous RBCs in Adults and Premature Infants. BioRBC 2 µg/mL	NA days Standard Deviation NA Adults were never studied at the 2 µg/mL BioRBC density. The is because our protocol did not allow for normal adults to be studied at this BioRBC density.	60 days Standard Deviation 20
RBC Survival (Life Span) in Days of Multiple, Distinct BioRBC Density Populations of Transfused Autologous RBCs in Adults and Premature Infants. BioRBC 6 µg/mL	120 days Standard Deviation 10	60 days Standard Deviation 20
RBC Survival (Life Span) in Days of Multiple, Distinct BioRBC Density Populations of Transfused Autologous RBCs in Adults and Premature Infants. BioRBC 18 µg/mL	120 days Standard Deviation 10	60 days Standard Deviation 20
RBC Survival (Life Span) in Days of Multiple, Distinct BioRBC Density Populations of Transfused Autologous RBCs in Adults and Premature Infants. BioRBC 54 µg/mL	95 days Standard Deviation 10	60 days Standard Deviation 20
RBC Survival (Life Span) in Days of Multiple, Distinct BioRBC Density Populations of Transfused Autologous RBCs in Adults and Premature Infants. BioRBC 162 µg/mL	80 days Standard Deviation 10	NA days Standard Deviation NA This was not tested infants because of prior results in adults.

PRIMARY outcome

Timeframe: for up to 4 months

Population: This only applies to infants since no adults received allogeneic biotin labeled RBC

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

Outcome measures

Outcome measures
Measure	PPG1A - Adults n=40 Participants 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. 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.	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. 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. Transfused Biotin RBCs - Infants Phase III: Phase III (infants) to be determined upon completion of Phase II (infants).
RBC Survival (Life Span) in Days of Multiple, Distinct BioRBC Density Populations of Transfused Allogeneic RBCs in Premature Infants. BioRBC 2 µg/mL	60 days Standard Deviation 20	—
RBC Survival (Life Span) in Days of Multiple, Distinct BioRBC Density Populations of Transfused Allogeneic RBCs in Premature Infants. BioRBC 6 µg/mL	60 days Standard Deviation 20	—
RBC Survival (Life Span) in Days of Multiple, Distinct BioRBC Density Populations of Transfused Allogeneic RBCs in Premature Infants. BioRBC 18 µg/mL	60 days Standard Deviation 20	—
RBC Survival (Life Span) in Days of Multiple, Distinct BioRBC Density Populations of Transfused Allogeneic RBCs in Premature Infants. BioRBC 54 µg/mL	60 days Standard Deviation 20	—

SECONDARY outcome

Timeframe: 4 to 5 mo post transfusion of biotin RBCs

IgG gel card agglutination test that was developed in our laboratory

Outcome measures

Outcome measures
Measure	PPG1A - Adults n=9 Participants 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. 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.	PPG1B - Infants n=53 Participants 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. 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. Transfused Biotin RBCs - Infants Phase III: Phase III (infants) to be determined upon completion of Phase II (infants).
Number of Participants With Positive Antibody Screen in Response to Biotin-labeled RBCs.	3 Participants	0 Participants

SECONDARY outcome

Timeframe: 4 months

Population: Only applies to allogeneic RBCs and all infants did not have autologous transfusions

Outcome measures

Outcome measures
Measure	PPG1A - Adults n=40 Participants 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. 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.	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. 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. Transfused Biotin RBCs - Infants Phase III: Phase III (infants) to be determined upon completion of Phase II (infants).
Survival of Allogeneic RBCs in Days as Measured by the Antigenic Method Using Flow Cytometry for Comparison With BioRBC in Premature Infants	70 days Standard Deviation 20	—

Adverse Events

PPG1A - Adults

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

PPG1B - Infants

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

John A. Widness, M.D.

University of Iowa

Phone: 319-356-8102

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place