Physiologic Effects of RBC Transfusion

Phase 4

Terminated

• Conditions: Red Blood Cell Transfusion
• Interventions: Biological: Fresh red blood cell (RBC) transfusion; Biological: Storage-aged red blood cell (RBC) transfusion; Device: Electronic infusion pump

• Registration Number: NCT02566577
• Lead Sponsor: Emory University

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2013-07
• Study First Submitted: 2015-10-01
• Study First Submitted QC: 2015-10-01
• Study First Posted: 2015-10-02
• Primary Completion: 2018-03
• Study Completion: 2018-03
• Results First Submitted: 2019-03-29
• Status Verified: 2019-05
• Results First Submitted QC: 2019-05-03
• Last Update Submitted: 2019-05-03
• Results First Posted: 2019-05-24
• Last Update Posted: 2019-05-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Subjects with any condition resulting in transfusion-dependent anemia

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Fresh RBC transfusion/Storage-aged RBC transfusion	Fresh red blood cell (RBC) transfusion	Subjects will receive a transfusion of packed red blood cell (RBC) units of fresh blood (\<10 days old) followed by a transfusion of packed RBC units of storage-aged (\>21 days old) blood.
Storage-aged RBC transfusion/Fresh RBC transfusion	Electronic infusion pump	Subjects will receive a transfusion of packed red blood cell (RBC) units of storage-aged (\>21 days old) blood followed by a transfusion of packed RBC units of fresh blood (\<10 days old).
Storage-aged RBC transfusion/Fresh RBC transfusion	Fresh red blood cell (RBC) transfusion	Subjects will receive a transfusion of packed red blood cell (RBC) units of storage-aged (\>21 days old) blood followed by a transfusion of packed RBC units of fresh blood (\<10 days old).
Fresh RBC transfusion/Storage-aged RBC transfusion	Storage-aged red blood cell (RBC) transfusion	Subjects will receive a transfusion of packed red blood cell (RBC) units of fresh blood (\<10 days old) followed by a transfusion of packed RBC units of storage-aged (\>21 days old) blood.
Fresh RBC transfusion/Storage-aged RBC transfusion	Electronic infusion pump	Subjects will receive a transfusion of packed red blood cell (RBC) units of fresh blood (\<10 days old) followed by a transfusion of packed RBC units of storage-aged (\>21 days old) blood.
Storage-aged RBC transfusion/Fresh RBC transfusion	Storage-aged red blood cell (RBC) transfusion	Subjects will receive a transfusion of packed red blood cell (RBC) units of storage-aged (\>21 days old) blood followed by a transfusion of packed RBC units of fresh blood (\<10 days old).

Primary Outcome Measures

Name	Time	Method
Change in Reactive Hyperemic Index (RHI)	Baseline (prior to transfusion), Day 1 (first post-transfusion day)	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.
Change in Flow-mediated Vasodilation (FMD)	Baseline (prior to transfusion), Day 1 (first post-transfusion day)	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.

Secondary Outcome Measures

Name	Time	Method
Respiratory Exchange Ratio (RER):	Day 1 (first post-transfusion day)	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.
Peak VO2 Lean	Day 1 (first post-transfusion day)	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.
Maximal Oxygen Uptake (VO2Max)	Day 1 (first post-transfusion day)	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.
O2 Pulse	Day 1 (first post-transfusion day)	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.
Change in Oxidative Stress Markers	Baseline (prior to transfusion), Day 1 (first post-transfusion day)	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.
Change in Levels of IL-6	Baseline (prior to transfusion), Day 1 (first post-transfusion day)	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.
Change in Levels of IL-2	Baseline (prior to transfusion), Day 1 (first post-transfusion day)	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.
Change in Levels of Nitric Oxide Metabolites	Baseline (prior to transfusion), Day 1 (first post-transfusion day)	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.
Change in High-sensitivity C-reactive Protein (hsCRP)hsCRP	Baseline (prior to transfusion), Day 1 (first post-transfusion day)	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.

Trial Locations

Locations (1)

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States