- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02566577
Physiologic Effects of RBC Transfusion
May 3, 2019 updated by: Arshed A. Quyyumi, Emory University
Physiologic Effects of RBC Storage in Chronic Transfusion Recipients: Vasoreactivity, Exercise Capacity, and Oxygen Consumption
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.
Study Overview
Status
Terminated
Conditions
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 Type
Interventional
Enrollment (Actual)
15
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Georgia
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Atlanta, Georgia, United States, 30322
- Emory University Hospital
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
19 years to 78 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Fresh RBC transfusion/Storage-aged 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.
|
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.
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.
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.
|
Active Comparator: Storage-aged RBC transfusion/Fresh 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).
|
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.
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.
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Flow-mediated Vasodilation (FMD)
Time Frame: 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.
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Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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Change in Reactive Hyperemic Index (RHI)
Time Frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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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)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximal Oxygen Uptake (VO2Max)
Time Frame: 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.
|
Day 1 (first post-transfusion day)
|
Respiratory Exchange Ratio (RER):
Time Frame: 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.
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Day 1 (first post-transfusion day)
|
O2 Pulse
Time Frame: 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.
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Day 1 (first post-transfusion day)
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Peak VO2 Lean
Time Frame: 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.
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Day 1 (first post-transfusion day)
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Change in Oxidative Stress Markers
Time Frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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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.
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Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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Change in Levels of Nitric Oxide Metabolites
Time Frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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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.
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Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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Change in High-sensitivity C-reactive Protein (hsCRP)hsCRP
Time Frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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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.
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Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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Change in Levels of IL-6
Time Frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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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.
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Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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Change in Levels of IL-2
Time Frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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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.
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Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Arshed Quyyumi, MD, FACC, Emory University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2013
Primary Completion (Actual)
March 1, 2018
Study Completion (Actual)
March 1, 2018
Study Registration Dates
First Submitted
October 1, 2015
First Submitted That Met QC Criteria
October 1, 2015
First Posted (Estimate)
October 2, 2015
Study Record Updates
Last Update Posted (Actual)
May 24, 2019
Last Update Submitted That Met QC Criteria
May 3, 2019
Last Verified
May 1, 2019
More Information
Terms related to this study
Other Study ID Numbers
- IRB00064523
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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