Trial Outcomes & Findings for Transfusion of Biotin-Labeled Red Blood Cells (NCT NCT03364686)

Last Updated: 2022-04-21

Results Overview

This will be determined using enumeration of biotinylated red blood cells obtained by flow cytometry from blood samples obtained at various time points from subjects with specified genetic mutations, compared with control subjects without the specified mutation. Percentage of Biotin Labeled Red Blood Cells is determined by Biotin Labeled Red Blood Cells in circulation at each time point/baseline Biotin Labeled Red Blood Cells in circulation x 100.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

24 hours, 30 days and 60 days after transfusion

Results posted on

2022-04-21

Participant Flow

Participant milestones

Participant milestones
Measure	Biotin-Labeled Red Blood Cells Infusion Each participant will receive 2 transfusions of biotin labeled red blood cells. Biotin-Labeled Red Blood Cells: We will collect 500 mL of blood. The blood will be processed and split into two bags and labeled with a naturally occurring vitamin, biotin. The blood will then be re-infused back into the same participant at 2 time points (5-7 days and 35-42 days after storage).
Overall Study STARTED	6
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Biotin-Labeled Red Blood Cells Infusion Each participant will receive 2 transfusions of biotin labeled red blood cells. Biotin-Labeled Red Blood Cells: We will collect 500 mL of blood. The blood will be processed and split into two bags and labeled with a naturally occurring vitamin, biotin. The blood will then be re-infused back into the same participant at 2 time points (5-7 days and 35-42 days after storage).
Overall Study Physician Decision	2

Baseline Characteristics

Transfusion of Biotin-Labeled Red Blood Cells

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Biotin-Labeled Red Blood Cells Infusion n=6 Participants Each participant will receive 2 transfusions of biotin labeled red blood cells. Biotin-Labeled Red Blood Cells: We will collect 500 mL of blood. The blood will be processed and split into two bags and labeled with a naturally occurring vitamin, biotin. The blood will then be re-infused back into the same participant at 2 time points (5-7 days and 35-42 days after storage).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 hours, 30 days and 60 days after transfusion

Population: The blood sample at 24 hours from one of the 4 completed subjects was not collected.

Outcome measures

Outcome measures
Measure	Biotin-Labeled Red Blood Cells Infusion n=3 Participants Each participant will receive 2 transfusions of biotin labeled red blood cells. Biotin-Labeled Red Blood Cells: We will collect 500 mL of blood. The blood will be processed and split into two bags and labeled with a naturally occurring vitamin, biotin. The blood will then be re-infused back into the same participant at 2 time points (5-7 days and 35-42 days after storage).
Percentage of Biotin Labeled Red Blood Cells Percentage of Fresh Biotin Labeled Red Blood Cells at 24 Hours	99.2 percentage of biotin labeled RBC Interval 99.2 to 99.3
Percentage of Biotin Labeled Red Blood Cells Percentage of Fresh Biotin Labeled Red Blood Cells at Day 30	77.2 percentage of biotin labeled RBC Interval 74.7 to 79.6
Percentage of Biotin Labeled Red Blood Cells Percentage of Fresh Biotin Labeled Red Blood Cells at Day 60	54.3 percentage of biotin labeled RBC Interval 49.5 to 59.2
Percentage of Biotin Labeled Red Blood Cells Percentage of Aged Biotin Labeled Red Blood Cells at 24 Hours	99.2 percentage of biotin labeled RBC Interval 99.1 to 99.3
Percentage of Biotin Labeled Red Blood Cells Percentage of Aged Biotin Labeled Red Blood Cells at Day 30	75.9 percentage of biotin labeled RBC Interval 72.9 to 78.9
Percentage of Biotin Labeled Red Blood Cells Percentage of Aged Biotin Labeled Red Blood Cells at Day 60	51.9 percentage of biotin labeled RBC Interval 45.9 to 57.8

SECONDARY outcome

Timeframe: 5-7 days and 35-42 days following blood donation

This will be quantified as percent hemolysis, which accounts for the levels of RBC-derived free hemoglobin in response to cold storage. We will define the associations between the primary endpoints and the quantification of storage hemolysis. Quantification of storage hemolysis is based on this equation: (sample hematocrit x levels of free hemoglobin obtained after centrifugation measured in the supernatant / the total amount of sample hemoglobin before centrifugation) x 100.

Outcome measures

Outcome measures
Measure	Biotin-Labeled Red Blood Cells Infusion n=4 Participants Each participant will receive 2 transfusions of biotin labeled red blood cells. Biotin-Labeled Red Blood Cells: We will collect 500 mL of blood. The blood will be processed and split into two bags and labeled with a naturally occurring vitamin, biotin. The blood will then be re-infused back into the same participant at 2 time points (5-7 days and 35-42 days after storage).
The Percentage of Storage Hemolysis 5-7 days	0.27 percentage of storage hemolysis Standard Deviation 0.09
The Percentage of Storage Hemolysis 35-42 days	0.21 percentage of storage hemolysis Standard Deviation 0.14

SECONDARY outcome

Timeframe: 5-7 days and 35-42 days following blood donation

This will be quantified by the evaluation of osmotic stress assays. We will define the associations between the primary endpoints and the quantification of osmotic hemolysis. The percent osmotic hemolysis is determined by this equation: (supernatant cell-free hemoglobin of pink test-treated RBCs / total amount of hemoglobin) x 100.

Outcome measures

Outcome measures
Measure	Biotin-Labeled Red Blood Cells Infusion n=4 Participants Each participant will receive 2 transfusions of biotin labeled red blood cells. Biotin-Labeled Red Blood Cells: We will collect 500 mL of blood. The blood will be processed and split into two bags and labeled with a naturally occurring vitamin, biotin. The blood will then be re-infused back into the same participant at 2 time points (5-7 days and 35-42 days after storage).
The Percentage of Red Blood Cell Osmotic Hemolysis 5-7 days	7.4 percentage of osmotic hemolysis Standard Deviation 4.66
The Percentage of Red Blood Cell Osmotic Hemolysis 35-42 days	7.9 percentage of osmotic hemolysis Standard Deviation 6.86

SECONDARY outcome

Timeframe: 5-7 days and 35-42 days following blood donation

This will be quantified by the evaluation of oxidative stress assays. We will define the associations between the primary endpoints and the quantification of oxidative hemolysis. The percent osmotic hemolysis is determined by this equation: (supernatant cell-free hemoglobin of 2,2'-azobis-2-methyl-propanimidamide, dihydrochloride treated RBCs - supernatant cell-free hemoglobin of untreated red blood cells / total amount of hemoglobin) x 100.

Outcome measures

Outcome measures
Measure	Biotin-Labeled Red Blood Cells Infusion n=4 Participants Each participant will receive 2 transfusions of biotin labeled red blood cells. Biotin-Labeled Red Blood Cells: We will collect 500 mL of blood. The blood will be processed and split into two bags and labeled with a naturally occurring vitamin, biotin. The blood will then be re-infused back into the same participant at 2 time points (5-7 days and 35-42 days after storage).
The Percentage of Red Blood Cell Oxidative Hemolysis 5-7 days	39.93 percentage of oxidative hemolysis Standard Deviation 12.45
The Percentage of Red Blood Cell Oxidative Hemolysis 35-42 days	46.90 percentage of oxidative hemolysis Standard Deviation 21.92

POST_HOC outcome

Timeframe: up to 165 days

Population: The fresh stored blood sample from one participant was not collected and analyzed.

This will be determined using enumeration of biotinylated red blood cells obtained by flow cytometry from blood samples obtained at various time points from subjects.

Outcome measures

Outcome measures
Measure	Biotin-Labeled Red Blood Cells Infusion n=4 Participants Each participant will receive 2 transfusions of biotin labeled red blood cells. Biotin-Labeled Red Blood Cells: We will collect 500 mL of blood. The blood will be processed and split into two bags and labeled with a naturally occurring vitamin, biotin. The blood will then be re-infused back into the same participant at 2 time points (5-7 days and 35-42 days after storage).
Length of Time Biotin-labeled Red Blood Cells Can be Detected Following Infusion Fresh Stored Cells	135 days Standard Deviation 12
Length of Time Biotin-labeled Red Blood Cells Can be Detected Following Infusion Stored Cells	104 days Standard Deviation 12

Adverse Events

Biotin-Labeled Red Blood Cells Infusion

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Biotin-Labeled Red Blood Cells Infusion n=6 participants at risk Each participant will receive 2 transfusions of biotin labeled red blood cells. Biotin-Labeled Red Blood Cells: We will collect 500 mL of blood. The blood will be processed and split into two bags and labeled with a naturally occurring vitamin, biotin. The blood will then be re-infused back into the same participant at 2 time points (5-7 days and 35-42 days after storage).
Blood and lymphatic system disorders Weakly positive antibodies	16.7% 1/6 • Number of events 1 • Day 125-150 post blood transfusion

Additional Information

Darrell J. Triulzi, MD

University of Pittsburgh

Phone: 412-209-7304

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place