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

Sickle Cell Disease Clinical Trial

Official title:

Harmful Effects of Transfusion of Older Stored Red Cells: Iron and Inflammation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01534676
• Other study ID #: AAAI1111
• Secondary ID: R01HL098014
• Status: Terminated
• Phase: N/A
• First received: February 14, 2012
• Last updated: May 15, 2015
• Start date: February 2012

Study information

• Verified date: May 2015
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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 the investigators 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.

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 Food and Drug Administration (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 New York 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 (NYBC) within 3 days of collection. Washing older stored red blood cell (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 Columbia University Medical Center (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 intravenous (IV) line prior to transfusion, immediately after transfusion, 1 hour after transfusion, and 2 hours after transfusion.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. primary completion date: February 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 1 Year to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease
• Thalassemia

Intervention

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.

Locations

Country	Name	City	State
United States	Columbia University Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Non-transferrin-bound iron		2 hours after transfusion	Yes
Secondary	transferrin saturation		2 hours following transfusion	No
Secondary	pro-inflammatory cytokines	Interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 will be measured.	2 hours after transfusion	No