Donor Iron Deficiency Study - Red Blood Cells From Iron-deficient Donors: Recovery and Storage Quality

A Randomized Trial to Determine if RBCs From Donors With Iron Deficient Erythropoiesis Have Decreased Post-transfusion RBC Recovery and Whether Iron Repletion Improves Recovery

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02889133

Acronym

DIDS

Enrollment

Registered

2016-09-05

Start date

2017-01-31

Completion date

2021-10-05

Last updated

2024-06-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Iron Deficiency

Keywords

Iron deficiency, Transfusion, Blood donation

Brief summary

Primary Hypothesis * The 24-hour post-transfusion RBC recovery of units obtained from donors exhibiting iron-deficient erythropoiesis will not meet FDA standards for clinical use. * The 24-hour post-transfusion RBC recovery of units obtained after intravenous iron repletion will improve significantly and will meet FDA standards for clinical use.

Detailed description

Iron deficiency is common among regular blood donors, but the recovery and quality of red blood cell (RBC) units from iron-deficient donors has not been rigorously examined. Evidence from both animal and human studies indicate that when the iron supply for erythropoiesis is inadequate, the RBCs produced have multiple metabolic defects that impair their ability to tolerate refrigerated storage. Studies in a mouse model demonstrated decreased post-transfusion recovery of refrigerator-stored RBCs obtained from iron-deficient donors. The planned studies will identify human donors at greatest risk of providing RBCs with poor post-transfusion recovery by using a combination of a decreased serum ferritin concentration and increased RBC zinc protoporphyrin, as described below. To evaluate unequivocally the role of iron deficiency in poor posttransfusion RBC recovery, intravenous iron will be used for iron repletion.

Interventions

DRUGIron-dextran

Approved for clinical use: 1-gram dose IV - diluted in 500 mL, one pint normal saline.

DRUGSaline

Salt water IV - 500 mL, one pint normal saline.

PROCEDUREBlood Donation

Standard process of collecting and storing blood and blood components (approximately 450 mL, or a pint of blood). Following donation, the blood will be leukoreduced, packed, and stored in AS-3 solution.

PROCEDURE24-hour PTR

The way the FDA determines how good blood is for transfusion is called a radioactive 51-Chromium 24-hour post-transfusion red cell recovery study. The purpose is to measure how many of the transfused red cells are still in circulation (being pumped by the heart through blood vessels) 24 hours after transfusion. In order to measure the percent of red cells that are still in circulation, a small amount of the donated blood will be radioactively labeled. This will be infused in one arm and then blood will be collected from the other arm at different time points to measure how much of the transfused red cells are still in circulation.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Yes

Inclusion criteria

1. 18-75 years old; 2. healthy (by self report); 3. body weight \>110 lbs; 4. female hematocrit \>=38%, male hematocrit \>39%; 5. frequent blood donor (men ≥2 and female ≥1 RBC unit donations in past year); 6. ferritin \<=15 ng/mL; and 7. zinc protoporphyrin \>=60 µmol/mol heme.

Exclusion criteria

1. ineligible for donation based on the New York Blood Center donor autologous questionnaire; 2. taking iron supplementation; 3. C-reactive protein \>10 mg/L; 4. sickle cell trait; 5. systolic blood pressure \>180 or \<90 mm Hg, diastolic blood pressure \>100 or \<50 mm Hg; 6. heart rate \<50 or \>100; 7. temperature \>99.5°F prior to donation; 8. temperature \>100.4°F or subjective feeling of illness prior to 51-Chromium 24-hour RBC recovery study (to avoid the subject having a concurrent illness that may affect post-transfusion recovery); 9. positive results on standard blood donor infectious disease testing; 10. pregnancy; 11. taking, or planning to take, iron supplements; and 12. history of severe asthma requiring hospitalization, allergic eczema (atopic dermatitis), or other atopic allergy causing anaphylaxis.

Design outcomes

Primary

Measure	Time frame	Description
51-Chromium 24-hour Post-transfusion RBC Recovery of Units	Performed 42 days after blood donation	Comparison of the percentage change in 51-Chromium-labeled RBCs remaining from pre- and 24 hour post-transfusion measurement between the Iron Repletion and the Placebo group. The post-transfusion recovery represents the percent of 51-Chromium-labeled RBCs remaining in circulation 24 hours after infusion as compared to an extrapolated time zero measurement.

Secondary

Measure	Time frame	Description
Serum Ferritin	End of participation (e.g., ~6 months)	Measured in a clinical laboratory. Will be used to determine the association between pre-donation ferritin levels and post-transfusion recovery along with the effect of treatment on ferritin levels.
Hemoglobin	End of participation (e.g., ~6 months)	Measured in a clinical laboratory. Will be used to determine the association between pre-donation hemoglobin levels and post-transfusion recovery along with the effect of treatment on hemoglobin levels.
Reticulocyte Hemoglobin	End of participation (e.g., ~6 months)	Measured in a clinical laboratory. Will be used to determine the association between pre-donation reticulocyte hemoglobin levels and post-transfusion recovery along with the effect of treatment on reticulocyte hemoglobin levels.
Soluble Transferrin Receptor	End of participation (e.g., ~6 months)	Measured in a clinical laboratory. Will be used to determine the association between pre-donation soluble transferrin receptor levels and post-transfusion recovery along with the effect of treatment on soluble transferrin receptor levels.
Hepcidin	End of participation (e.g., ~6 months)	Measured as a research use only test in a research laboratory using an ELISA from Intrinsic LifeSciences. Will be used to determine the association between pre-donation hepcidin levels and post-transfusion recovery along with the effect of treatment on hepcidin levels.
Transferrin Saturation	End of participation (e.g., ~6 months)	Measured in a clinical laboratory. Will be used to determine the association between pre-donation transferrin saturation levels and post-transfusion recovery along with the effect of treatment on transferrin saturation levels.
SF-36 Physical Functioning Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
SF-36 Role Functioning/Physical Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
SF-36 Role Functioning/Emotional Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
RBC Zinc Protoporphyrin Levels	End of participation (e.g., ~6 months)	Measured in a clinical laboratory. Will be used to determine the association between pre-donation zinc protoporphyrin levels and post-transfusion recovery along with the effect of treatment on zinc protoporphyrin levels.
SF-36 Emotional Well-being Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
SF-36 Social Functioning Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
SF-36 Pain Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
SF-36 General Health Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
SF-36 Health Change Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.
Beck Depression Inventory (BDI) II Score	End of participation (e.g., ~6 months)	Evaluating subjects' depression using the Beck Depression Inventory-II survey. Scores range from 0-63 with higher scores indicating more severe depression.
Beck Anxiety Inventory (BAI) Score	End of participation (e.g., ~6 months)	Evaluating subjects' anxiety using the Beck Anxiety Inventory survey. Scores range from 0-63 with higher scores indicating more severe anxiety.
Global Fatigue Index (GFI) Score	End of participation (e.g., ~6 months)	Evaluating subjects' fatigue using the Multidimensional Assessment of Fatigue (MAF) survey. Scores range from 1-50 with higher scores indicating more severe fatigue.
Restless Legs Syndrome Rating Scale Score	End of participation (e.g., ~6 months)	Evaluating subjects' symptoms of restless leg syndrome using the Restless Legs Syndrome Rating Scale survey. Scores range from 0-40 with higher scores indicating more severe symptoms.
SF-36 Energy/Fatigue Score	End of participation (e.g., ~6 months)	Evaluating subjects' health status using Short Form (SF)-36 question survey. Scores range from 0-100% with higher scores indicating better health.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Iron Repletion Subjects will donate blood donation and undergo 24-hour PTR and receive IV iron-dextran. After 5 months, subjects will donate blood again and undergo 24-hour PTR. Iron-dextran: Approved for clinical use: 1-gram dose IV - diluted in 500 mL, one pint normal saline. Saline: Salt water IV - 500 mL, one pint normal saline. Blood Donation: Standard process of collecting and storing blood and blood components (approximately 450 mL, or a pint of blood). Following donation, the blood will be leukoreduced, packed, and stored in AS-3 solution. 24-hour PTR: The way the FDA determines how good blood is for transfusion is called a radioactive 51-Chromium 24-hour post-transfusion red cell recovery study. The purpose is to measure how many of the transfused red cells are still in circulation (being pumped by the heart through blood vessels) 24 hours after transfusion. In order to measure the percent of red cells that are still in circulation, a small amount of the donated blood will be radioactively labeled. This will be infused in one arm and then blood will be collected from the other arm at different time points to measure how much of the transfused red cells are still in circulation.	39
Placebo Subjects will donate blood donation and undergo 24-hour PTR and receive IV saline. After 5 months, subjects will donate blood again and undergo 24-hour PTR. Iron-dextran: Approved for clinical use: 1-gram dose IV - diluted in 500 mL, one pint normal saline. Saline: Salt water IV - 500 mL, one pint normal saline. Blood Donation: Standard process of collecting and storing blood and blood components (approximately 450 mL, or a pint of blood). Following donation, the blood will be leukoreduced, packed, and stored in AS-3 solution. 24-hour PTR: The way the FDA determines how good blood is for transfusion is called a radioactive 51-Chromium 24-hour post-transfusion red cell recovery study. The purpose is to measure how many of the transfused red cells are still in circulation (being pumped by the heart through blood vessels) 24 hours after transfusion. In order to measure the percent of red cells that are still in circulation, a small amount of the donated blood will be radioactively labeled. This will be infused in one arm and then blood will be collected from the other arm at different time points to measure how much of the transfused red cells are still in circulation.	40
Total	79

Withdrawals & dropouts

Period	Reason	FG000	FG001
Completed Primary Outcome	Chromium labeling failure	1	0
Completed Primary Outcome	COVID-19/Illness	4	2
Completed Primary Outcome	Lost to Follow-up	1	1
Completed Primary Outcome	Manufacturing error	3	8
Completed Primary Outcome	Protocol Violation	1	0
Completed Primary Outcome	Subject did not meet donor criteria	0	1
Completed Secondary Outcomes	COVID-19/illness	4	2
Completed Secondary Outcomes	Lost to Follow-up	1	1
Completed Secondary Outcomes	Protocol Violation	1	0
Completed Secondary Outcomes	Subject could not donate blood after randomization	0	2

Baseline characteristics

Characteristic	Iron Repletion	Total	Placebo
Age, Continuous	33 years	34 years	34 years
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants	9 Participants	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants	70 Participants	37 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	6 Participants	10 Participants	4 Participants
Race (NIH/OMB) Black or African American	1 Participants	2 Participants	1 Participants
Race (NIH/OMB) More than one race	7 Participants	11 Participants	4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	25 Participants	56 Participants	31 Participants
Region of Enrollment United States	39 participants	79 participants	40 participants
Sex: Female, Male Female	27 Participants	54 Participants	27 Participants
Sex: Female, Male Male	12 Participants	25 Participants	13 Participants
Weight	73 kg	68 kg	66 kg

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 39	0 / 40
other Total, other adverse events	1 / 39	3 / 40
serious Total, serious adverse events	0 / 39	1 / 40

Outcome results

Primary

51-Chromium 24-hour Post-transfusion RBC Recovery of Units

Comparison of the percentage change in 51-Chromium-labeled RBCs remaining from pre- and 24 hour post-transfusion measurement between the Iron Repletion and the Placebo group. The post-transfusion recovery represents the percent of 51-Chromium-labeled RBCs remaining in circulation 24 hours after infusion as compared to an extrapolated time zero measurement.

Time frame: Performed 42 days after blood donation

Population: See participant flow for primary outcome for subject number explanation.

Arm	Measure	Value (MEDIAN)
Iron Repletion	51-Chromium 24-hour Post-transfusion RBC Recovery of Units	1.6 percentage change
Placebo	51-Chromium 24-hour Post-transfusion RBC Recovery of Units	-0.4 percentage change

Secondary

Beck Anxiety Inventory (BAI) Score

Evaluating subjects' anxiety using the Beck Anxiety Inventory survey. Scores range from 0-63 with higher scores indicating more severe anxiety.

Time frame: End of participation (e.g., ~6 months)