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| ID | Type | Description | Link |
|---|---|---|---|
| 1P50HL081015 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| Bloodworks | OTHER |
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This study is designed to provide information on patients' immune response after exposure to transfused blood.
Blood transfusions may have opposite immune effects on patients. One is sensitization. The other is immunosuppression. The magnitude of these effects in patients who are not on chemotherapy is unknown.
These effects are thought to be due largely to white blood cells present in the transfusion product. "Leukofiltration" and "gamma-irradiation" are the special treatments that deplete white blood cells. A combination of leukofiltration and gamma-irradiation pretreatment of donor blood is thought to deplete the white blood cells most effectively.
In this study, patients scheduled for cardiac surgery are randomly assigned to receive blood products pretreated in one of three ways: untreated, filtered or filtered and irradiated. If their physician orders transfusions, they will receive products assigned to their group. Patients are asked to provide two blood samples during the 4 weeks after surgery.
Studies will measure changes in antibody to HLA and in cells that regulate the immune response. The levels of sensitization and immunosuppression will be correlated to the transfusion products received.
Blood transfusions may have opposite immune effects on patients. One is sensitization. The other is immunosuppression. The magnitude of this problem in patients who are not on chemotherapy is unknown.
Of patients who do receive donor blood, 50-90 percent become sensitized (make antibody) to HLA proteins present on white blood cells in the donor blood. This is an undesired effect in patients who need an organ or stem cell transplant, as it increases the risk of rejection. Another effect of receiving a blood transfusion, immunosuppression, causes a decreased immune response that compromises patients' ability to fight off infection or tumor cells.
These effects - sensitization and immunosuppression - are thought to be due largely to white blood cells present in the transfusion product. Doctors order specially pretreated blood transfusions that have been depleted of white blood cells with the aim of minimizing risks in an "immunocompromised" patient. "Leukofiltration" and "gamma-irradiation" are the special treatments that deplete white blood cells. A combination of leukofiltration and gamma-irradiation pretreatment of donor blood is thought to deplete the white blood cells most effectively. Therefore, blood is pretreated both ways before it is given to patients who need a stem cell transplant or others who are immunosuppressed.
Sometimes the pretreated leukofiltration and gamma-irradiated blood is used for "regular" patients who are not immunocompromised so the blood is used before it expires and not wasted. However, doctors do not know for sure whether these expensive pretreatments are really beneficial for "regular" patients such as those undergoing cardiac surgery and whether they would change the risk of developing sensitization or immunosuppression.
In this study, patients are randomly assigned to receive blood products pretreated in one of three ways: untreated, filtered or filtered and irradiated. If their physician orders transfusions, they will receive products assigned to their group. Patients are asked to provide two blood samples during the 4 weeks after surgery. Studies will measure changes in antibody to HLA and in cells that regulate the immune response.
It is unknown which treatment (leukofiltration with or without gamma-irradiation compared to no pretreatment) is most beneficial in patients who are not immunosuppressed.
This study is designed to provide information on patients' immune response after exposure to transfused blood. This information may be useful to caring for patients in the future who require transfusion for cardiac surgery.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator | Blood components with no additional treatment |
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| 2 | Experimental | Blood components leukoreduced |
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| 3 | Experimental | Blood components leukoreduced and irradiated |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Standard blood components | Biological | Transfusion, if ordered by physician, with unfiltered red blood cells and apheresis platelets |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Changes in the Production of Antibody to HLA Antigens | Blood samples were collected prior to surgery and at two times after surgery. Serum was tested for the presence of IgG antibody to HLA. the results of the samples collected after surgery were compared to those in the sample collected prior to surgery. | 0 to 5 weeks after surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Changes in the Number or Cytokine Profile of CD4 T Regulatory Cells or NKT Cells. Number of Participants With Changes in Numbers of Cells Producing TGFB1. Number of Participants With Changes in Secretion of Cytokines | Blood samples were collected prior to surgery and at two times after surgery. White blood cells were isolated and frozen. The thawed cells were tested for the numbers and phenotype of regulatory cells and for the production of regulatory cytokines. Results obtained from samples collected after surgery were compared to the results obtained from the sample collected prior to surgery. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Karen Nelson, PhD | Bloodworks | Principal Investigator |
| Gabriel Aldea, MD | University of Washington | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwest Hospital | Seattle | Washington | 98133 | United States | ||
| University of Washington Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31608454 | Derived | Nelson KA, Aldea GS, Warner P, Latchman Y, Gunasekera D, Tamir A, Gernsheimer T, Bolgiano D, Slichter SJ. Transfusion-related immunomodulation: gamma irradiation alters the effects of leukoreduction on alloimmunization. Transfusion. 2019 Nov;59(11):3396-3404. doi: 10.1111/trf.15555. Epub 2019 Oct 13. |
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There were 7 individuals who consented but were not randomized: late discovery of exclusionary criteria, surgery cancelled, individual withdrew.
Patients scheduled for cardiac surgery at the U. Washington or an affiliated program at Northwest Hospital had the study explained to them by the clinical team including a clinical research coordinator and consent was obtained.
Recruitment began in August of 2006 and extended until August of 2010.
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| ID | Title | Description |
|---|---|---|
| FG000 | 4. No Transfusion | This arm includes participants from arms 1, 2 and 3 who did not require nor receive transfusions of red blood cells or platelets while they were on study. These participants were moved to this arm after study completion, prior to analysis. |
| FG001 | 1. Standard | Patients received unfiltered red blood cells and apheresis platelets if transfusions were ordered by their providers while on study (2 days prior to surgery to 30 days post surgery). |
| FG002 | 2. Leukoreduced | Patients received filter leukoreduced red blood cells and apheresis platelets collected leukoreduced if transfusions were ordered by their providers while on study (2 days prior to surgery to 30 days post surgery). |
| FG003 | 3. Leukoreduced Gamma Irradiated | Patients received filter leukoreduced red blood cells that were gamma irradiated and apheresis platelets collected leukoreduced and gamma irradiated if transfusions were ordered by their providers while on study (2 days prior to surgery to 30 days post surgery). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 4. No Transfusion | This arm includes participants from arms 1, 2 and 3 who did not require nor receive transfusions of red blood cells or platelets while they were on study. These participants were moved to this arm after study completion, prior to analysis. |
| BG001 | 1. Standard |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Changes in the Production of Antibody to HLA Antigens | Blood samples were collected prior to surgery and at two times after surgery. Serum was tested for the presence of IgG antibody to HLA. the results of the samples collected after surgery were compared to those in the sample collected prior to surgery. | Antibody tests were invalid for some participants in Arm 1. Their sera contained interfering substances. | Posted | Count of Participants | Participants | 0 to 5 weeks after surgery |
|
Duration on study - 30 days post surgery.
The only study related adverse event would have been due to the phlebotomy to collect study blood samples and none were reported.
Participants received transfusion therapy as ordered by their clinical team. None of the blood products were experimental.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 4. No Transfusion | This arm includes participants from arms 1, 2 and 3 who did not require nor receive transfusions of red blood cells or platelets while they were on study. These participants were moved to this arm after study completion, prior to analysis. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Karen Nelson, PhD., Vice President Laboratories | Bloodworks Northwest (formerly Puget Sound Blood Center) | 206-689-6549 | knelson@bloodworksnw.org |
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| ID | Term |
|---|---|
| D011827 | Radiation |
| ID | Term |
|---|---|
| D055585 | Physical Phenomena |
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Individuals who consented for study were scheduled for cardiac surgery. They were randomized to one of three arms to receive blood components prepared by different, but clinically acceptable processes. If they required transfusion from 2 days prior to surgery until 30 days post surgery they received study product. Blood samples were collected prior to surgery and at two points after surgery.
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Clinical teams caring for patients were not masked. Laboratory personnel were masked until all testing completed.
| Leukoreduced blood components | Biological | Transfusion, if ordered by a physician, of leukoreduced red blood cells and apheresis platelets |
|
| Leukoreduced and irradiated | Biological | Transfusion, if ordered by physician, of gamma irradiated leukoreduced red blood cells and gamma irradiated apheresis platelets |
|
| 0 to 5 weeks after surgery |
| Seattle |
| Washington |
| 98195 |
| United States |
| Physician Decision |
|
Patients received unfiltered red blood cells and apheresis platelets if transfusions were ordered by their providers while on study (2 days prior to surgery to 30 days post surgery). |
| BG002 | 2. Leukoreduced | Patients received filter leukoreduced red blood cells and apheresis platelets collected leukoreduced if transfusions were ordered by their providers while on study (2 days prior to surgery to 30 days post surgery). |
| BG003 | 3. Leukoreduced Gamma Irradiated | Patients received filter leukoreduced red blood cells that were gamma irradiated and apheresis platelets collected leukoreduced and gamma irradiated if transfusions were ordered by their providers while on study (2 days prior to surgery to 30 days post surgery). |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex/Gender, Customized | Data on sex/gender was not recorded as neither the primary nor the secondary outcomes used those measures in the analysis. All patients presenting to the service who did not have one or more exclusionary criteria were approached for consent to the study. | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| OG001 |
| 1. Standard |
Patients received unfiltered red blood cells and apheresis platelets if transfusions were ordered by their providers while on study (2 days prior to surgery to 30 days post surgery). |
| OG002 | 2. Leukoreduced | Patients received filter leukoreduced red blood cells and apheresis platelets collected leukoreduced if transfusions were ordered by their providers while on study (2 days prior to surgery to 30 days post surgery). |
| OG003 | 3. Leukoreduced Gamma Irradiated | Patients received filter leukoreduced red blood cells that were gamma irradiated and apheresis platelets collected leukoreduced and gamma irradiated if transfusions were ordered by their providers while on study (2 days prior to surgery to 30 days post surgery). |
|
|
| Secondary | Number of Participants With Changes in the Number or Cytokine Profile of CD4 T Regulatory Cells or NKT Cells. Number of Participants With Changes in Numbers of Cells Producing TGFB1. Number of Participants With Changes in Secretion of Cytokines | Blood samples were collected prior to surgery and at two times after surgery. White blood cells were isolated and frozen. The thawed cells were tested for the numbers and phenotype of regulatory cells and for the production of regulatory cytokines. Results obtained from samples collected after surgery were compared to the results obtained from the sample collected prior to surgery. | The study used stringent criteria for acceptance of these cellular assays. Invalid tests were not included in the analysis, therefor the numbers reported in the Outcome Measures table do not add up to the number analyzed for each test. | Posted | Count of Participants | Participants | 0 to 5 weeks after surgery |
|
|
|
| 0 |
| 124 |
| 0 |
| 124 |
| EG001 | 1. Standard | Patients received unfiltered red blood cells and apheresis platelets if transfusions were ordered by their providers while on study (2 days prior to surgery to 30 days post surgery). | 0 | 49 | 0 | 49 |
| EG002 | 2. Leukoreduced | Patients received filter leukoreduced red blood cells and apheresis platelets collected leukoreduced if transfusions were ordered by their providers while on study (2 days prior to surgery to 30 days post surgery). | 0 | 56 | 0 | 56 |
| EG003 | 3. Leukoreduced Gamma Irradiated | Patients received filter leukoreduced red blood cells that were gamma irradiated and apheresis platelets collected leukoreduced and gamma irradiated if transfusions were ordered by their providers while on study (2 days prior to surgery to 30 days post surgery). | 0 | 51 | 0 | 51 |
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| Number of CD4+ IL4+ iNKT cells |
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| Number of CD4+ IFNg+ iNKT cells |
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| Number of CD4- IL4+ iNKT cells |
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| Number of CD4- INFg+ iNKT cells |
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| IL-10 produced by PBMC |
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| CD4+Number of CD25+FoxP3+ T cells |
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| Number of CD4+CD25+CTLA4+ T cells |
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| Not increased |
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| Not increased |
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| Not increased |
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| Not increased |
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| Not increased |
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| Not increased |
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| Not increased |
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