Physiologic Effects of RBC Transfusion

Red Blood Cell Transfusion Clinical Trial

Official title:

Physiologic Effects of RBC Storage in Chronic Transfusion Recipients: Vasoreactivity, Exercise Capacity, and Oxygen Consumption

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02566577
• Other study ID #: IRB00064523
• Status: Terminated
• Phase: Phase 4
• Start date: July 2013
• Est. completion date: March 2018

Study information

• Verified date: May 2019
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine how red blood cell transfusions, particularly the length of storage time of units of packed red blood cells, affects the cardiovascular function in patients receiving transfusions. This study will also determine the most ideal way of storing and processing blood, and assess how transfusion affects a person's ability to exercise and how their blood vessels relax and contract.

Description:

The purpose of this study is determine red blood cell transfusion, particularly the length of storage time of units of packed red blood cells, affects cardiovascular function in patients receiving transfusions. Transfusion of red blood cells is often used clinically in patients with low red blood cell counts in order to prevent disease progression and death. Recent studies suggest that the use of "aged" versus "fresh" red blood cells is associated with worse clinical outcomes, but there is no clear understanding on how this happens. The investigators want to determine the most ideal way of storing and processing blood, and learn how transfusion affects the ability to exercise in the study subjects and assess the relaxation and contraction of the blood vessels.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: March 2018
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 80 Years

Eligibility

Inclusion Criteria:

• Subjects with any condition resulting in transfusion-dependent anemia

Exclusion Criteria:

• Age <21 or >80 years

• Pregnancy

• Acute infection in previous 4 weeks

• Active substance abuse within the past year

• Inability to give informed consent

• Inability to return for follow-up

• The presence of alloantibodies that would limit the blood bank's ability to obtain correctly aged red blood cell (RBC) units

Related Conditions & MeSH terms

• Red Blood Cell Transfusion

Intervention

Biological:
• Fresh red blood cell (RBC) transfusion
1 or 2 cross-matched, packed red blood cells (RBC) units from fresh (<10 days old) blood, as ordered by the attending physician, will be given as an intravenous infusion via a programmable electronic infusion pump (Baxter, Inc) over a period of 1 hour per unit.
• Storage-aged red blood cell (RBC) transfusion
1 or 2 cross-matched, packed red blood cells (RBC) units from storage-aged (>21 days old) blood, as ordered by the attending physician, will be given as an intravenous infusion via a programmable electronic infusion pump (Baxter, Inc) over a period of 1 hour per unit.

Device:
• Electronic infusion pump
A programmable, electronic infusion pump (Baxter, Inc) will be used for intravenous transfusion of units of packed red blood cells (RBC). The pump will be programmed to deliver 1 unit of packed RBC per hour.

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Emory University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Flow-mediated Vasodilation (FMD)	Brachial artery flow-mediated dilation (FMD) will be performed by using ultrasonography. The brachial artery of the non-dominant arm will be imaged using a high-resolution 13 MHz ultrasound transducer. A blood pressure cuff on the forearm will be inflated to supra-systolic pressures to produce 5 minutes of ischemia. After cuff deflation, imaging of the brachial artery will be performed continuously for the next 120 seconds and the flow-mediated dilation will be calculated. Change in FMD is the percent change in the diameter of the brachial artery from baseline (prior to transfusion) to Day 1 (first post-transfusion day). A higher FMD indicates better nitric oxide-dependent endothelial function.	Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Primary	Change in Reactive Hyperemic Index (RHI)	Reactive Hyperemia Index (RHI) will be measured using Pulsatile Arterial Tonometry (PAT). Baseline blood pressure of both hands is measured and PAT probes are placed one on each hand at the same finger (fingers 2, 3 or 4). Following an equilibration period of 10 minutes, the blood pressure cuff will be inflated to 60 mmHg above systolic pressure for 5 minutes followed by deflation of the cuff and the pulsatile recordings from both study and control fingers will be measured. RHI will be calculated from the ratio of the digital pulse volume during reactive hyperemia (following cuff deflation) and baseline. A higher RHI indicates better nitric oxide-dependent endothelial function.	Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Secondary	Maximal Oxygen Uptake (VO2Max)	Subjects will undergo graded treadmill testing following American Heart Association guidelines using the modified Balke protocol. A treadmill with full metabolic cart will be used for the cardiopulmonary testing. Maximal oxygen uptake (VO2Max) is the value achieved when the oxygen uptake remains stable despite a progressive increase in the intensity of exercise. The VO2Max will be calculated from the cardiac output and the arteriovenous oxygen difference during peak exercise. VO2Max is expressed in milliliters of oxygen per minute per kilogram of body weight (ml/min/kg). A higher VO2Max indicates better vascular reactivity.	Day 1 (first post-transfusion day)
Secondary	Respiratory Exchange Ratio (RER):	Subjects will undergo graded treadmill testing following American Heart Association guidelines using the modified Balke protocol. A treadmill with full metabolic cart will be used for the cardiopulmonary testing. RER is the ratio of VCO2 (carbon dioxide output) to VO2 (oxygen uptake). A higher RER indicates better vascular reactivity.	Day 1 (first post-transfusion day)
Secondary	O2 Pulse	Subjects will undergo graded treadmill testing following American Heart Association guidelines using the modified Balke protocol. A treadmill with full metabolic cart will be used for the cardiopulmonary testing. O2 (oxygen) pulse is the amount of O2 consumed from the volume of blood delivered to tissues by each heartbeat; this index is calculated as: O2 pulse = VO2 / heart rate. A higher O2 pulse indicates better vascular reactivity.	Day 1 (first post-transfusion day)
Secondary	Peak VO2 Lean	Subjects will undergo graded treadmill testing following American Heart Association guidelines using the modified Balke protocol. A treadmill with full metabolic cart will be used for the cardiopulmonary testing. Peak VO2 lean is the peak oxygen uptake adjusted for lean body mass and is reported as a lean body weight-adjustment parameter in mL/kg per minute.	Day 1 (first post-transfusion day)
Secondary	Change in Oxidative Stress Markers	Oxidative stress will be measured using high-performance liquid chromatography (HPLC) to collect plasma cystine, cysteine, glutathione, and glutathione disulfide levels. Higher levels of cystine, cysteine, glutathione, and glutathione disulfide indicate higher levels of vascular inflammation.	Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Secondary	Change in Levels of Nitric Oxide Metabolites	Nitric oxide metabolites like nitrite, nitrate, S-nitrosothiols (SNO-Hb and SNO-thiol) will be measured from blood samples using high-performance liquid chromatography (HPLC). Higher levels of nitric oxide metabolites indicate higher levels of nitric oxide (NO) synthesis and better vascular reactivity.	Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Secondary	Change in High-sensitivity C-reactive Protein (hsCRP)hsCRP	Levels of high-sensitivity C-reactive protein (hsCRP) in the blood will be measured by using Dade Behring nephelometry. Higher levels of hsCRP indicate increased vascular inflammation.	Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Secondary	Change in Levels of IL-6	Plasma IL-6 concentration will be measured by enzyme-linked immunosorbent assay (ELISA). Change is the difference in the levels of IL-6 from baseline to Day 1 (first post-transfusion day). Higher concentrations of IL-6 indicate increased vascular inflammation.	Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Secondary	Change in Levels of IL-2	Plasma IL-2 concentration will be measured by enzyme-linked immunosorbent assay (ELISA). Change is the difference in the levels of IL-2 from baseline to Day 1 (first post-transfusion day). Higher concentrations of IL-2 indicate increased vascular inflammation.	Baseline (prior to transfusion), Day 1 (first post-transfusion day)