Adverse Effects of Red Blood Cell Transfusions: A Unifying Hypothesis (Aim 3)

NCT02280655 | Completed Phase 2 Results DMC

• 1 other identifier: IRB00015316a
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Transfusion of red blood cells is often used in critically ill patients with low red blood cell counts to prevent disease progression and death. Recent studies suggest that the use of "aged" versus "fresh" red blood cells are associated with worse clinical outcomes. There is evidence that red blood cells work with the cells lining our blood vessels to produce a variety of substances that normally cause arteries to relax and increase blood supply. Two of these substances are called nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). The investigators are trying to determine the nature of these substances in human beings when they are transfused "aged" versus "fresh" red blood cells. The purpose of the study is to test the effects of transfusing "aged" versus "fresh" red blood cells in volunteers with traditional cardiovascular risk factors (high blood pressure, diabetes, high cholesterol, and tobacco use) on 1) the degree of relaxation in the arteries and subsequent changes in blood flow, 2) blood levels of oxidant molecules, 3) inflammation, and 4) stem cells. A similar study with healthy volunteers are further described in NCT00838331.

Conditions

Cardiovascular Diseases

Keywords

Blood Transfusions

Outcome Measures

Primary Outcomes (2)

• Brachial Artery Flow-mediated Dilation (FMD) After Fresh Red Blood Cells (RBCs) Transfusions vs. Storage-aged Red Blood Cells (saRBCs) Transfusions at Baseline

  Ultrasonography of the brachial artery performed at the bedside using a high-resolution 10-megahertz (MHz) ultrasound transducer before and after suprasystolic inflation of a blood pressure cuff for 5 minutes in the ipsilateral upper arm. Brachial artery FMD was calculated as (hyperemic diameter - baseline diameter)/baseline diameter × 100.

  Baseline

• Brachial Artery Flow-mediated Dilation (FMD) After Fresh Red Blood Cells (RBCs) Transfusions vs. Storage-aged Red Blood Cells (saRBCs) Transfusions at 24 Hours After Transfusion

  Ultrasonography of the brachial artery performed at the bedside using a high-resolution 10-megahertz (MHz) ultrasound transducer before and after suprasystolic inflation of a blood pressure cuff for 5 minutes in the ipsilateral upper arm. Brachial artery FMD was calculated as (hyperemic diameter -24 hour diameter)/24 hour diameter × 100.

  24 hours after transfusion

Study Arms (2)

Storage-aged red blood cells (saRBCs)

ACTIVE COMPARATOR

Subjects with cardiovascular disease (CVD) received a transfusion with older stored red blood cells (RBCs) units. The units had been stored for greater than 21 days.

Biological: Storage-aged red blood cells (saRBCs) units

Fresh red blood cells (RBCs)

ACTIVE COMPARATOR

Subjects with cardiovascular disease (CVD) received a transfusion with fresh red blood cells (RBCs) units. The units had been stored for less than 14 days.

Biological: Fresh red blood cells units

Interventions

Storage-aged red blood cells (saRBCs) units BIOLOGICAL

Packed RBCs units stored for greater than 21 days, with a mean storage duration of 29.6 ± 4.9 days (mean ± SD)

Storage-aged red blood cells (saRBCs)

Fresh red blood cells units BIOLOGICAL

Packed RBCs units stored for less than 14 days, with a mean storage duration of 9.6 ± 3.9 days (mean ± SD)

Fresh red blood cells (RBCs)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Inpatient or outpatient at Emory University Hospital who's physicians have ordered a transfusion of packed red blood cells (pRBCs) of 1 or more units
• Cardiovascular risk factors (hypercholesterolemia, diabetes, hypertension, and tobacco smoking) or known cardiovascular disease) will be carefully documented for each subject
• Cardiac risk factors are defined as follows:
• Hypercholesterolemia: Defined as serum low density lipoprotein cholesterol \> 140 mg/dL if not currently on lipid-lowering therapy or \> 100 mg/dL if on lipid-lowering therapy
• Diabetes: Defined as having fasting blood glucose sample of \> 126 mg/dL or a hemoglobin A1c of \> 7% or being treated with diabetes medications such as oral hypoglycemic agents, insulin sensitizing agents, or subcutaneous insulin
• Smoking: active tobacco use, 20 cigarettes per day for the past year
• Hypertension: Blood pressure of \> 140/90 or currently on anti-hypertensive medications
• Cardiovascular disease: known coronary artery disease by angiogram or documented myocardial infarction

You may not qualify if:

• Pregnancy
• Previous transfusion within one week.
• Inability to give informed consent
• On oral or IV nitrate therapy
• On vasopressor agents
• Active illicit drug use

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Limitations and Caveats

Only patients receiving routine transfusions were included in the study, thus excluding critically ill/actively bleeding patients requiring emergent transfusions.

Results Point of Contact

• Title: Dr. John D. Roback
• Organization: Emory University

jroback@emory.edu

404-712-1774

Study Officials

• John Roback, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 29, 2014
• First Posted: October 31, 2014
• Study Start: April 1, 2009
• Primary Completion: November 1, 2012
• Study Completion: October 1, 2013
• Last Updated: April 11, 2016
• Results First Posted: December 4, 2014

Record last verified: 2016-04

Locations

US (1)