Effects of Transfusion of Older Red Blood Cells on Patients With Hemoglobinopathies

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2012 by Columbia University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Columbia University
ClinicalTrials.gov Identifier:
NCT01534676
First received: February 14, 2012
Last updated: February 16, 2012
Last verified: February 2012
  Purpose

Epidemiologic studies suggest that older stored blood is associated with worse outcomes in certain hospitalized patients. Storage of red cells is associated with a storage lesion and the survival of transfused red cells decreases with increasing storage time, thus older blood is associated with an increased acute delivery of hemoglobin-iron to the reticuloendothelial system. The investigators have preliminary data in healthy human volunteers suggesting that delivery of a significant iron load to the reticuloendothelial system from aged red cells leads to the elaboration of a potentially toxic form of iron known as non-transferrin--bound iron. The investigators will extend these results by testing whether a similar effect is seen in chronically transfused patients with hemoglobinopathies. This patient population will also allow us to test whether iron- chelation therapy is beneficial in this setting. Finally, the investigators will also test whether washing or cryopreserving the red blood cells has any effect on this outcome. These findings may explain the immunomodulatory effects of older stored blood in patients and will help us develop safer transfusion products for patients.


Condition Intervention
Sickle Cell Disease
Thalassemia
Biological: Transfusion

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Harmful Effects of Transfusion of Older Stored Red Cells: Iron and Inflammation

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Non-transferrin-bound iron [ Time Frame: 2 hours after transfusion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • transferrin saturation [ Time Frame: 2 hours following transfusion ] [ Designated as safety issue: No ]
  • pro-inflammatory cytokines [ Time Frame: 2 hours after transfusion ] [ Designated as safety issue: No ]
    Interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 will be measured.


Estimated Enrollment: 60
Study Start Date: February 2012
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: Transfusion
    1 or 2 unit transfusion of fresh (defined as less than 14 days of storage) packed red blood cells stored in an additive solution vs. 1 or 2 unit transfusion of older (defined as greater than 28 days of storage) packed red blood cells stored in an additive solution.
    Other Names:
    • Washed red blood cells
    • Cryopreserved red blood cells
Detailed Description:

Below is a summary of the procedures to be performed on each donor participant followed by the procedures for each recipient participant:

Donor participants:

Screening 2 tubes of blood will be drawn from a peripheral vein to perform a complete blood count and to perform blood bank testing (e.g. antibody screen, red cell phenotype). All donors who qualify based on criteria listed below, and have a red cell phenotype that matches a specific study patient will be recruited to perform 4 double red blood cell donations at the New York Blood Center over a 3 -year period based on the recipient's transfusion schedule. At least 112 days will be allotted between each blood donation (as per FDA regulations). Donors will have to pass the standard screening process (per FDA regulations) performed at the Blood Center, including standard infectious disease testing. Any donor failing screening due to infectious disease testing will be notified by trained counselors at the NY Blood Center and will be excluded from study participation. In addition, a new dedicated donor will replace any participant that drops out of the study, or becomes ineligible on subsequent attempts after successfully donating.

Recipient participants:

Study transfusions will be scheduled according to the patient's regular transfusion schedule such that one unit of the double red blood cell donation can be transfused "fresh" (i.e. prior to 14 days of storage) and the other unit can be transfused "old" (i.e. after 28 days of storage). The 8 transfusion events are listed below:

  1. "Fresh" transfusion while patient OFF chelation therapy
  2. "Old" transfusion while patient OFF chelation therapy
  3. "Fresh" transfusion while patient ON chelation therapy
  4. "Old" transfusion while patient ON chelation therapy
  5. "Fresh" washed transfusion while patient OFF chelation therapy
  6. "Old" washed transfusion while patient OFF chelation therapy
  7. "Fresh" transfusion while patient OFF chelation therapy
  8. Cryopreserved transfusion while patient OFF chelation therapy

For the 6 transfusions off chelation therapy, the patient will be asked to discontinue chelation therapy for 3 days prior to the scheduled transfusion. The washed and cryopreserved red cell units will be obtained per standard operating procedure from the New York Blood Center. Cryopreservation of one of the two donated double red blood cell units will be performed using Standard Operating Procedures at the New York Blood Center within 3 days of collection. Washing older stored RBC units and deglycerolizing cryopreserved red blood cell units will both be performed within 24 hours of transfusion, also by NYBC Standard Operating Procedures. Deglycerolization and washing of red blood cell units will each be performed using an automatic cell washing system (COBE 2991, CaridianBCT). All red cell units will be issued by the CUMC blood bank following standard operating procedures and a crossmatch.

The transfusion will take place in the Pediatric Hematology Clinic infusion center following standard procedures. An intravenous line will be placed and 4 tubes of blood will be drawn from the IV line prior to transfusion, immediately after transfusion, 1 hour after transfusion, and 2 hours after transfusion.

  Eligibility

Ages Eligible for Study:   1 Year to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria (Recipient):

  • specific, well-characterized hemoglobinopathy
  • chronic simple transfusion therapy (transfusion episodes < 6 weeks apart in frequency)
  • chronic iron chelation therapy
  • not pregnant by self-report and not planning pregnancy
  • age > 1 year old

Exclusion Criteria (Recipient):

  • clinically unstable
  • treatment for mental illness
  • imprisonment
  • institutionalization

Inclusion Criteria (Donor):

  • 21-65 years of age
  • male weight > 130 lbs, female weight > 150 lbs
  • male height > 5'1", female height > 5'5"
  • hemoglobin > 15.0 g/dL
  • reasonably certain of intention to stay in New York City metropolitan area for study duration
  • previously tolerated red blood cell donation

Exclusion Criteria (Donor):

  • ineligible for donation based on New York Blood Center blood donor screening questionnaire
  • systolic blood pressure < 90 or > 180 mm Hg, diastolic blood pressure < 50 or > 100 mm Hg
  • heart rate < 50 or > 100
  • temperature > 99.5 F prior to donation
  • positive by standard infectious disease testing performed on blood donors
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01534676

Contacts
Contact: Eldad Hod, MD 212-342-5648 eh2217@columbia.edu
Contact: Shruti Sharma, MS 212-342-5648 ss3558@columbia.edu

Locations
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Eldad Hod, MD       eh2217@columbia.edu   
Contact: Shruti Sharma, MS       ss3558@columbia.edu   
Principal Investigator: Steven Spitalnik, MD         
Sub-Investigator: Eldad Hod, MD         
Sub-Investigator: Margaret Lee, MD         
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Steven Spitalnik, MD Columbia University
  More Information

No publications provided

Responsible Party: Columbia University
ClinicalTrials.gov Identifier: NCT01534676     History of Changes
Other Study ID Numbers: AAAI1111, R01HL098014
Study First Received: February 14, 2012
Last Updated: February 16, 2012
Health Authority: United States: Federal Government

Keywords provided by Columbia University:
iron
transfusion
red blood cells
sickle cell disease
thalassemia
blood donors

Additional relevant MeSH terms:
Anemia, Sickle Cell
Hemoglobinopathies
Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on July 28, 2014