Blood Transfusion Complications
Conditions
Keywords
Transfusion, RBC, cardiac, surgery, transfusion related acute lung injury (TRALI), transfusion associated circulatory overload (TACO)
Brief summary
This study is designed to determine if point-of-care washing of allogeneic Leukocyte-Reduced Red Blood Cells reduces pulmonary complications when compared to standard-of-care Leukocyte-Reduced Red Blood Cells in a cardiac surgical population.
Interventions
BIOLOGICALPoint-of-care washed red blood cell transfusion.
BIOLOGICALStandard of care red blood cell transfusion.
Sponsors
Duke University
Vitalant Research Institute
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age equal to or greater than 18 years of age. * Scheduled to have cardiac bypass surgery at Mayo Clinic in Rochester, Minnesota or Duke University Medical Center in Durham, North Carolina * At risk for needing at least 4 units of blood during/after surgery
Exclusion criteria
* Emergency surgery * Immunoglobulin A (IgA) deficiency * History of severe recurrent transfusion reactions * Refusal to receive allogeneic blood products * Refusal to provide informed consent * Prevalent lung injury prior to randomization * Prevalent congestive heart failure prior to randomization * Expected hospital stay \< 48 hours * Not anticipated to survive \> 48 hours * Previously enrolled in this trial * No plan for placement of a pulmonary artery catheter * Use of home oxygen therapy * Complex RBC antibody profiles * Need for the use of irradiated RBCs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Haptoglobin | Pre transfusion to study day 5 or hospital discharge, approximately 5 days | Change in Haptoglobin from pre-transfusion to worst (minimum) post-transfusion |
| Biomarkers Associated With Transfusion-Related Acute Lung Injury and Transfusion Associated Circulatory Overload. | 18 hours after the initiation of the first red blood cell transfusion. | This panel of biomarkers measures inflammation, altered coagulation, and endothelial activation all of which play key roles in the pathogenesis of lung injury. |
| Number of Off-protocol Transfusions | Day of surgery. Approximately 1 day. | The number of standard issued red blood cell units that were transfused to study participants in the washed red blood cell arm of the trial. Additionally, emergency red blood cell transfusions in the standard issued arm of the trial that were administered outside of the study protocol were also included to the definition of off protocol transfusion. |
| Change in Recipient Hemoglobin | Pre to 6 hours post transfusion | Change in Hemoglobin from pre-transfusion to post-transfusion |
| Change in Recipient Cell Free Hemoglobin(CFH) | Pre transfusion until study day 5 or hospital discharge, approximately 5 days | Change in CFH from pre-transfusion to worst (highest/maximum) post-transfusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Mechanical Ventilation | Up to hospital day 28, or discharge, whichever comes first | Number of hours subject received mechanical ventilation. |
| Duration of Oxygen Supplementation | Up to day 28, or hospital discharge, whichever comes first | Number of hours subjects received supplemental oxygen. |
| Sequential Organ Failure Assessment (SOFA) Score | Through postoperative day 5. | Worst SOFA score between Day 1 and Day 5. SOFA scores range from 0-24 with 0 meaning no organ dysfunction and 24 means severe dysfunction of all organ systems evaluated. Each of 6 organ systems are scored on a 0-4 scale with the cumulative score being the total SOFA score. |
| Hospital Length of Stay | Up to day 28 | Number of days subject remained in the hospital following their surgical procedure. If the number of days the subject remained in the hospital exceeded 28, a value of 28 is assigned. |
| Post Transfusion Respiratory Complications. | Up to day 28 | Development of transfusion-related lung injury (TRALI) or transfusion-associated circulatory overload (TACO). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care Red Blood Cell Transfusion Red blood cells that are administered in the normal fashion.
Standard of care red blood cell transfusion. | 85 |
| Point-of-Care Washed Red Blood Cell Transfusion Red blood cells that are washed at the point-of-care.
Point-of-care washed red blood cell transfusion. | 86 |
| Total | 171 |
Baseline characteristics
| Characteristic | Standard of Care Red Blood Cell Transfusion | Total | Point-of-Care Washed Red Blood Cell Transfusion |
|---|---|---|---|
| Age, Continuous | 66.1 years STANDARD_DEVIATION 11.4 | 65.6 years STANDARD_DEVIATION 11.7 | 65.0 years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 6 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 81 Participants | 159 Participants | 78 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 29 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) White | 66 Participants | 130 Participants | 64 Participants |
| Region of Enrollment United States | 85 participants | 171 participants | 86 participants |
| Sex: Female, Male Female | 43 Participants | 84 Participants | 41 Participants |
| Sex: Female, Male Male | 42 Participants | 87 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 85 | 3 / 86 |
| other Total, other adverse events | 0 / 85 | 0 / 86 |
| serious Total, serious adverse events | 0 / 85 | 7 / 86 |
Outcome results
Primary
Biomarkers Associated With Transfusion-Related Acute Lung Injury and Transfusion Associated Circulatory Overload.
This panel of biomarkers measures inflammation, altered coagulation, and endothelial activation all of which play key roles in the pathogenesis of lung injury.
Time frame: 18 hours after the initiation of the first red blood cell transfusion.
Population: Patients undergoing cardiac surgery who were predicted to be at high risk for requiring red blood cell transfusion.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Standard of Care Red Blood Cell Transfusion | Biomarkers Associated With Transfusion-Related Acute Lung Injury and Transfusion Associated Circulatory Overload. | IL-8 | 12 units on a scale (pg/ml) |
| Standard of Care Red Blood Cell Transfusion | Biomarkers Associated With Transfusion-Related Acute Lung Injury and Transfusion Associated Circulatory Overload. | vWF | 107 units on a scale (pg/ml) |
| Standard of Care Red Blood Cell Transfusion | Biomarkers Associated With Transfusion-Related Acute Lung Injury and Transfusion Associated Circulatory Overload. | RAGE | 3262 units on a scale (pg/ml) |
| Standard of Care Red Blood Cell Transfusion | Biomarkers Associated With Transfusion-Related Acute Lung Injury and Transfusion Associated Circulatory Overload. | SP_D | 7238 units on a scale (pg/ml) |
| Standard of Care Red Blood Cell Transfusion | Biomarkers Associated With Transfusion-Related Acute Lung Injury and Transfusion Associated Circulatory Overload. | PAI_1 | 73418 units on a scale (pg/ml) |
| Standard of Care Red Blood Cell Transfusion | Biomarkers Associated With Transfusion-Related Acute Lung Injury and Transfusion Associated Circulatory Overload. | ICAM_1 | 404914 units on a scale (pg/ml) |
| Standard of Care Red Blood Cell Transfusion | Biomarkers Associated With Transfusion-Related Acute Lung Injury and Transfusion Associated Circulatory Overload. | IL-6 | 101 units on a scale (pg/ml) |
| Point-of-Care Washed Red Blood Cell Transfusion | Biomarkers Associated With Transfusion-Related Acute Lung Injury and Transfusion Associated Circulatory Overload. | PAI_1 | 53829 units on a scale (pg/ml) |
| Point-of-Care Washed Red Blood Cell Transfusion | Biomarkers Associated With Transfusion-Related Acute Lung Injury and Transfusion Associated Circulatory Overload. | IL-6 | 105 units on a scale (pg/ml) |
| Point-of-Care Washed Red Blood Cell Transfusion | Biomarkers Associated With Transfusion-Related Acute Lung Injury and Transfusion Associated Circulatory Overload. | IL-8 | 15 units on a scale (pg/ml) |
| Point-of-Care Washed Red Blood Cell Transfusion | Biomarkers Associated With Transfusion-Related Acute Lung Injury and Transfusion Associated Circulatory Overload. | SP_D | 7061 units on a scale (pg/ml) |
| Point-of-Care Washed Red Blood Cell Transfusion | Biomarkers Associated With Transfusion-Related Acute Lung Injury and Transfusion Associated Circulatory Overload. | vWF | 111 units on a scale (pg/ml) |
| Point-of-Care Washed Red Blood Cell Transfusion | Biomarkers Associated With Transfusion-Related Acute Lung Injury and Transfusion Associated Circulatory Overload. | ICAM_1 | 404129 units on a scale (pg/ml) |
| Point-of-Care Washed Red Blood Cell Transfusion | Biomarkers Associated With Transfusion-Related Acute Lung Injury and Transfusion Associated Circulatory Overload. | RAGE | 4516 units on a scale (pg/ml) |
Primary
Change in Haptoglobin
Change in Haptoglobin from pre-transfusion to worst (minimum) post-transfusion
Time frame: Pre transfusion to study day 5 or hospital discharge, approximately 5 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care Red Blood Cell Transfusion | Change in Haptoglobin | -48.5 units on a scale (mg/dl) |
| Point-of-Care Washed Red Blood Cell Transfusion | Change in Haptoglobin | -54 units on a scale (mg/dl) |
Primary
Change in Recipient Cell Free Hemoglobin(CFH)
Change in CFH from pre-transfusion to worst (highest/maximum) post-transfusion
Time frame: Pre transfusion until study day 5 or hospital discharge, approximately 5 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care Red Blood Cell Transfusion | Change in Recipient Cell Free Hemoglobin(CFH) | 22.8 units on a scale (mg/dl) |
| Point-of-Care Washed Red Blood Cell Transfusion | Change in Recipient Cell Free Hemoglobin(CFH) | 23 units on a scale (mg/dl) |
Primary
Change in Recipient Hemoglobin
Change in Hemoglobin from pre-transfusion to post-transfusion
Time frame: Pre to 6 hours post transfusion
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care Red Blood Cell Transfusion | Change in Recipient Hemoglobin | 2.6 units on a scale (g/dl) |
| Point-of-Care Washed Red Blood Cell Transfusion | Change in Recipient Hemoglobin | 2.3 units on a scale (g/dl) |
Primary
Number of Off-protocol Transfusions
The number of standard issued red blood cell units that were transfused to study participants in the washed red blood cell arm of the trial. Additionally, emergency red blood cell transfusions in the standard issued arm of the trial that were administered outside of the study protocol were also included to the definition of off protocol transfusion.
Time frame: Day of surgery. Approximately 1 day.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care Red Blood Cell Transfusion | Number of Off-protocol Transfusions | 3 transfusions |
| Point-of-Care Washed Red Blood Cell Transfusion | Number of Off-protocol Transfusions | 22 transfusions |
Secondary
Duration of Mechanical Ventilation
Number of hours subject received mechanical ventilation.
Time frame: Up to hospital day 28, or discharge, whichever comes first
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care Red Blood Cell Transfusion | Duration of Mechanical Ventilation | 10.3 units on a scale (hours) |
| Point-of-Care Washed Red Blood Cell Transfusion | Duration of Mechanical Ventilation | 10.8 units on a scale (hours) |
Secondary
Duration of Oxygen Supplementation
Number of hours subjects received supplemental oxygen.
Time frame: Up to day 28, or hospital discharge, whichever comes first
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care Red Blood Cell Transfusion | Duration of Oxygen Supplementation | 84.7 units on a scale (hours) |
| Point-of-Care Washed Red Blood Cell Transfusion | Duration of Oxygen Supplementation | 89.5 units on a scale (hours) |
Secondary
Hospital Length of Stay
Number of days subject remained in the hospital following their surgical procedure. If the number of days the subject remained in the hospital exceeded 28, a value of 28 is assigned.
Time frame: Up to day 28
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care Red Blood Cell Transfusion | Hospital Length of Stay | 12 units on a scale (days) |
| Point-of-Care Washed Red Blood Cell Transfusion | Hospital Length of Stay | 12 units on a scale (days) |
Secondary
Post Transfusion Respiratory Complications.
Development of transfusion-related lung injury (TRALI) or transfusion-associated circulatory overload (TACO).
Time frame: Up to day 28
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard of Care Red Blood Cell Transfusion | Post Transfusion Respiratory Complications. | TACO | 7 participants |
| Standard of Care Red Blood Cell Transfusion | Post Transfusion Respiratory Complications. | TRALI | 1 participants |
| Point-of-Care Washed Red Blood Cell Transfusion | Post Transfusion Respiratory Complications. | TACO | 5 participants |
| Point-of-Care Washed Red Blood Cell Transfusion | Post Transfusion Respiratory Complications. | TRALI | 0 participants |
Secondary
Sequential Organ Failure Assessment (SOFA) Score
Worst SOFA score between Day 1 and Day 5. SOFA scores range from 0-24 with 0 meaning no organ dysfunction and 24 means severe dysfunction of all organ systems evaluated. Each of 6 organ systems are scored on a 0-4 scale with the cumulative score being the total SOFA score.
Time frame: Through postoperative day 5.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care Red Blood Cell Transfusion | Sequential Organ Failure Assessment (SOFA) Score | 12 units on a scale |
| Point-of-Care Washed Red Blood Cell Transfusion | Sequential Organ Failure Assessment (SOFA) Score | 13 units on a scale |