Red Blood Cell TransfusionPhase 4NCT02566577
Physiologic Effects of RBC Transfusion
A Phase 4 study testing Fresh red blood cell (RBC) transfusion, Storage-aged red blood cell (RBC) transfusion and Electronic infusion pump in people with Red Blood Cell Transfusion, run by Emory University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Red Blood Cell Transfusion
- What is being tested?
- Fresh red blood cell (RBC) transfusion, Storage-aged red blood cell (RBC) transfusion and Electronic infusion pump
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to Mar 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects with any condition resulting in transfusion-dependent anemia
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Red Blood Cell Transfusion
- Being tested
- Fresh red blood cell (RBC) transfusion, Storage-aged red blood cell (RBC) transfusion, Electronic infusion pump
- Keywords
- Chronic anemia, Cardiopulmonary testing, Transfusion-dependent anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fresh red blood cell (RBC) transfusionBiological
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) transfusionBiological
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.
Electronic infusion pumpDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Fresh RBC transfusion/Storage-aged RBC transfusion | Active comparator | 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. Receives: Biological: Fresh red blood cell (RBC) transfusion; Biological: Storage-aged red blood cell (RBC) transfusion; Device: Electronic infusion pump |
| Storage-aged RBC transfusion/Fresh RBC transfusion | Active comparator | 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). Receives: Biological: Fresh red blood cell (RBC) transfusion; Biological: Storage-aged red blood cell (RBC) transfusion; Device: Electronic infusion pump |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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.
Measured: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Secondary outcomes (9)
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.
Measured: Day 1 (first post-transfusion day)
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.
Measured: Day 1 (first post-transfusion day)
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.
Measured: Day 1 (first post-transfusion day)
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.
Measured: Day 1 (first post-transfusion day)
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.
Measured: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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.
Measured: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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.
Measured: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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.
Measured: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
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.
Measured: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2015 (estimated)
- Study startJul 2013
- Primary completionMar 2018
- Study completionMar 2018
Why it stopped: Difficulties in recruiting.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Red Blood Cell TransfusionStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Arshed A. Quyyumi, Emory University
- Investigators
- Arshed Quyyumi, MD, FACC, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02566577
- Sponsor's protocol ID
- IRB00064523
- Status last verified
- May 2019
- First submitted
- 1 Oct 2015
- Last updated
- 24 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Radford M, Estcourt LJ, Sirotich E, Pitre T, Britto J, Watson M, Brunskill SJ, Fergusson DA, Doree C, Arnold DM. Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support. Cochrane Database Syst Rev. 2024 May 23;5(5):CD011305. doi: 10.1002/14651858.CD011305.pub3.
PubMed 38780066
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physiologic Effects of RBC Storage in Chronic Transfusion Recipients: Vasoreactivity, Exercise Capacity, and Oxygen Consumption
- ClinicalTrials.gov ID
- NCT02566577
- Acronym / sponsor ID
- IRB00064523
- Conditions
- Red Blood Cell Transfusion
- Keywords
- Chronic anemia, Cardiopulmonary testing, Transfusion-dependent anemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulties in recruiting.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Mar 2018 (actual)
- Study completion
- Mar 2018 (actual)
- First posted
- 2 Oct 2015 (estimated)
- Results
- Posted 24 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fresh RBC transfusion/Storage-aged RBC transfusion | Active comparator | Biological: Fresh red blood cell (RBC) transfusion, Biological: Storage-aged red blood cell (RBC) transfusion, Device: Electronic infusion pumpSubjects 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 | Active comparator | Biological: Fresh red blood cell (RBC) transfusion, Biological: Storage-aged red blood cell (RBC) transfusion, Device: Electronic infusion pumpSubjects 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). |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Subjects with any condition resulting in transfusion-dependent anemia
Key exclusion criteria (7 listed)
- Age <21 or >80 years
- Pregnancy
- Acute infection in previous 4 weeks
- Active substance abuse within the past year
- Inability to give informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fresh red blood cell (RBC) transfusion1 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. | Biological | Fresh RBC transfusion/Storage-aged RBC transfusion, Storage-aged RBC transfusion/Fresh RBC transfusion |
| Storage-aged red blood cell (RBC) transfusion1 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. | Biological | Fresh RBC transfusion/Storage-aged RBC transfusion, Storage-aged RBC transfusion/Fresh RBC transfusion |
| Electronic infusion pumpA 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. | Device | Fresh RBC transfusion/Storage-aged RBC transfusion, Storage-aged RBC transfusion/Fresh RBC transfusion |
Primary outcome
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.
Change in Reactive Hyperemic Index (RHI)
Time frame: 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.
9 secondary outcomes
Maximal Oxygen Uptake (VO2Max)
Time frame: Day 1 (first post-transfusion day)
Respiratory Exchange Ratio (RER):
Time frame: Day 1 (first post-transfusion day)
O2 Pulse
Time frame: Day 1 (first post-transfusion day)
Peak VO2 Lean
Time frame: Day 1 (first post-transfusion day)
Change in Oxidative Stress Markers
Time frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Change in Levels of Nitric Oxide Metabolites
Time frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Change in High-sensitivity C-reactive Protein (hsCRP)hsCRP
Time frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Change in Levels of IL-6
Time frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Change in Levels of IL-2
Time frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38780066Radford M, Estcourt LJ, Sirotich E, Pitre T, Britto J, Watson M, Brunskill SJ, Fergusson DA, Doree C, Arnold DM. Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support. Cochrane Database Syst Rev. 2024 May 23;5(5):CD011305. doi: 10.1002/14651858.CD011305.pub3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arshed Quyyumi, MD, FACC principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fresh red blood cell (RBC) transfusion, Storage-aged red blood cell (RBC) transfusion and Electronic infusion pump in people with Red Blood Cell Transfusion, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Flow-mediated Vasodilation (FMD) (time frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02566577, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2019.