Intravenous High Dose Iron in Blood Donors - Full Text View

Purpose

2-3% of the population participates in blood donation programmes. Traditionally, safety issues in transfusion medicine have been concentrating on product and recipient safety. Extensive efforts including strict donor inclusion criteria and testing for important transmissible infections have substantially improved product quality. One of the most common risks of blood donation is iatrogenic iron deficiency. It may affect up to 30% of regular blood donors because each whole blood donation causes a loss of 200 to 250 mg of iron. Although this has been known for at least 50 years, iron deficiency is not routinely assessed or treated in this population. Contributing factors include donation frequency, lower weight and female gender. Women have lower iron reserves and in premenopausal women, the daily required amount of iron is higher than in men. Besides anemia, iron deficiency may lead to fatigue and impaired cognitive and physical performance. Oral iron substitution is often associated with significant gastrointestinal side effects leading to poor compliance. Today, intravenous (iv.) iron preparations are well tolerated and allow the application of a large dose of 1000mg in one visit. Our hypothesis is that in blood donors with iron deficiency intravenous iron is feasible and preferable to oral iron because of its high efficacy and optimal compliance with a similar safety profile that has been extensively studied in other populations than blood donors.

Condition	Intervention	Phase
Iron Deficiency	Drug: ferric carboxymaltose Drug: oral iron	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	High Dose Intravenous Iron in Blood Donors With Iron Deficiency: a Randomized, Controlled Trial

Resource links provided by NLM:

MedlinePlus related topics: Anemia Blood Transfusion and Donation Fatigue Iron

U.S. FDA Resources

Further study details as provided by Medical University of Graz:

Primary Outcome Measures:

transferrin saturation (%) at visit 1 (V1) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number of patients with adverse events of different grades [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

Other Outcome Measures:

Other parameters of iron metabolism and red blood count [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Subjective symptoms fatigue [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	200
Study Start Date:	September 2013
Estimated Study Completion Date:	August 2015
Estimated Primary Completion Date:	August 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Oral Iron oral iron in a corresponding dose of 10g (assuming an absorption of 10%, 100 capsules a 100mg iron each) taken over 8-12 weeks	Drug: oral iron
Experimental: Intravenous high dose iron high dose intravenous iron (ferric carboxymaltose, 1000mg)	Drug: ferric carboxymaltose

Detailed Description:

Iron deficiency is possibly the most prevalent worldwide nutritive deficiency and it has been estimated that > 500 million people have adverse effects as a result. Total body iron amounts to 3 to 4.5 grams, the largest part being bound to hemoglobin in red cells.

One of the most common risks of blood donation is iatrogenic iron deficiency which may affect up to 30% of regular blood donors. Each whole blood donation means a whole blood loss of 450 ml ±10% for the bag and additional samples for the required tests, corresponding to a loss of 200 to 300 mg of iron. It has been estimated that 10 apheresis donations equal 1 whole blood donation. Contributing factors include donation frequency, low body weight and female gender. In Austria, the maximal annual donation frequency is 50x for plasmapheresis, 26x for plateletpheresis and 4 (women) respectively 6x (men) for whole blood donations. Although the frequent donation-induced development of iron depletion has been recognized for at least 50 years, iron deficiency is not routinely assessed or treated in this population. Recently it was reported that the presence of pica, the bizarre consumption of nonnutritive substances such as ice cubes, is associated with a high probability of iron depletion in blood donors.

Contributing factors to a poor iron status in blood donors include donation frequency, lower weight and female gender. Women also have lower iron reserves and in premenopausal women, the daily required amount of iron is higher than in men. Besides anemia, iron deficiency may lead to fatigue and impaired cognitive and physical performance. Several trials have evaluated different regimens of iron substitution in blood donors and demonstrated good treatment compliance and efficacy in improving iron status. Oral iron substitution is often associated with significant gastrointestinal side effects leading to poor compliance. Today, high-dose intravenous (iv.) iron preparations are available, well tolerated and allow for the application of a large dose of 1000mg in one visit.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

age ≥18 years and ≤ 65 years
ferritin ≤ 30 ng/ml
fulfilment of the strict criteria for blood donation

Exclusion Criteria:

hemochromatosis
active infection
pregnancy or lactation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01787526

Contacts

Contact: Karin Amrein, MD, MSc	43/316/3850 ext 80798	karin.amrein@medunigraz.at
Contact: Camilla Drexler, MD	43/316/3850 ext 83066	camilla.drexler@klinikum-graz.at

Locations

Austria
Medical University of Graz	Not yet recruiting
Graz, Austria, 8036
Principal Investigator: Karin Amrein, MD, MSc
Sub-Investigator: Camilla Drexler, MD
Sub-Investigator: Nazanin Sareban, MD

Sponsors and Collaborators

Medical University of Graz

Investigators

Principal Investigator:

Karin Amrein, MD

Medical University Graz, Austria

More Information

Publications:

Amrein K, Valentin A, Lanzer G, Drexler C. Adverse events and safety issues in blood donation--a comprehensive review. Blood Rev. 2012 Jan;26(1):33-42. doi: 10.1016/j.blre.2011.09.003. Epub 2011 Oct 11. Review.

Semmelrock MJ, Raggam RB, Amrein K, Avian A, Schallmoser K, Lanzer G, Semmelrock HJ, Prueller F, Berghold A, Rohde E. Reticulocyte hemoglobin content allows early and reliable detection of functional iron deficiency in blood donors. Clin Chim Acta. 2012 Apr 11;413(7-8):678-82. doi: 10.1016/j.cca.2011.12.006. Epub 2011 Dec 23.

Newman B. Iron depletion by whole-blood donation harms menstruating females: the current whole-blood-collection paradigm needs to be changed. Transfusion. 2006 Oct;46(10):1667-81. Review. No abstract available.

Cable RG, Glynn SA, Kiss JE, Mast AE, Steele WR, Murphy EL, Wright DJ, Sacher RA, Gottschall JL, Tobler LH, Simon TL; NHLBI Retrovirus Epidemiology Donor Study-II (REDS-II). Iron deficiency in blood donors: the REDS-II Donor Iron Status Evaluation (RISE) study. Transfusion. 2012 Apr;52(4):702-11. doi: 10.1111/j.1537-2995.2011.03401.x. Epub 2011 Oct 24.

Brittenham GM. Iron deficiency in whole blood donors. Transfusion. 2011 Mar;51(3):458-61. doi: 10.1111/j.1537-2995.2011.03062.x.

Bianco C, Brittenham G, Gilcher RO, Gordeuk VR, Kushner JP, Sayers M, Chambers L, Counts RB, Aylesworth C, Nemo G, Alving B. Maintaining iron balance in women blood donors of childbearing age: summary of a workshop. Transfusion. 2002 Jun;42(6):798-805.

BAST G, PEISKER H, SCHUMANN HD. [Latent disorders caused by iron deficiency in frequent blood donors]. Langenbecks Arch Klin Chir Ver Dtsch Z Chir. 1956;283(3):280-90. German.

Moore RA, Gaskell H, Rose P, Allan J. Meta-analysis of efficacy and safety of intravenous ferric carboxymaltose (Ferinject) from clinical trial reports and published trial data. BMC Blood Disord. 2011 Sep 24;11:4. doi: 10.1186/1471-2326-11-4.

Birgegård G, Schneider K, Ulfberg J. High incidence of iron depletion and restless leg syndrome (RLS) in regular blood donors: intravenous iron sucrose substitution more effective than oral iron. Vox Sang. 2010 Nov;99(4):354-61. doi: 10.1111/j.1423-0410.2010.01368.x.

Responsible Party:	Medical University of Graz
ClinicalTrials.gov Identifier:	NCT01787526 History of Changes
Other Study ID Numbers:	1.0, 2013-000327-14
Study First Received:	February 6, 2013
Last Updated:	February 13, 2013
Health Authority:	Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Graz:

iron depletion, donor safety, blood donation, transfusion medicine, iron deficiency, intravenous iron, fatigue, restless legs syndrome, anemia

Additional relevant MeSH terms:

Anemia, Iron-Deficiency
Iron Metabolism Disorders
Anemia, Hypochromic
Anemia
Hematologic Diseases
Metabolic Diseases
Iron
Ferric Compounds

Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Hematinics
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 16, 2013

Intravenous High Dose Iron in Blood Donors (IronWoMan)