Blood Component TransfusionPhase 4NCT00810810
Immunomodulation Following Transfusion
A Phase 4 study testing Standard blood components, Leukoreduced blood components and Leukoreduced and irradiated in people with Blood Component Transfusion, run by University of Washington at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Blood Component Transfusion
- What is being tested?
- Standard blood components, Leukoreduced blood components and Leukoreduced and irradiated
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 287 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2006to Aug 2011
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least 18 year of age
- Scheduled for open heart surgery of cardiopulmonary bypass that involves: CABG, CABG with valve, aneurysm repair
- Urgent or elective surgery
Who cannot join
- Scheduled for open heart surgery of cardiopulmonary bypass that involves: placement of a ventricular assist device, cardiac transplantation, aortic dissection repair
- Emergent surgery
- participation in other clinical research studies within 30 days of randomization.
- Immunosuppressive treatment.
- Refuse blood transfusion
- Disease or condition placing subject at undue risk or decision of attending doctor.
- Condition requiring high volume transfusion therapy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Northwest Hospital
Seattle, Washington, 98133
University of Washington Medical Center
Seattle, Washington, 98195
About this study
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.
Read more
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.
Read the detailed description
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.
- Conditions
- Blood Component Transfusion
- Being tested
- Standard blood components, Leukoreduced blood components, Leukoreduced and irradiated
- Keywords
- Blood Component Transfusion, Leukoreduction, HLA antibody, Immunosuppression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard blood componentsBiological
Transfusion, if ordered by physician, with unfiltered red blood cells and apheresis platelets
Leukoreduced blood componentsBiological
Transfusion, if ordered by a physician, of leukoreduced red blood cells and apheresis platelets
Leukoreduced and irradiatedBiological
Transfusion, if ordered by physician, of gamma irradiated leukoreduced red blood cells and gamma irradiated apheresis platelets
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Blood components with no additional treatment Receives: Biological: Standard blood components |
| 2 | Experimental | Blood components leukoreduced Receives: Biological: Leukoreduced blood components |
| 3 | Experimental | Blood components leukoreduced and irradiated Receives: Biological: Leukoreduced and irradiated |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 0 to 5 weeks after surgery
Secondary outcomes (1)
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.
Measured: 0 to 5 weeks after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2008 (estimated)
- Study startJul 2006
- Primary completionAug 2010
- Study completionAug 2011
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 Blood Component TransfusionStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 287 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Bloodworks
- Responsible party
- Principal investigator, Karen Nelson, University of Washington
- Investigators
- Karen Nelson, PhD, Principal investigator, BloodworksGabriel Aldea, MD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00810810
- Sponsor's protocol ID
- 29792
- Other IDs
- 1P50HL081015
- Status last verified
- Nov 2017
- First submitted
- 17 Dec 2008
- Last updated
- 26 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 31608454
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunomodulation Following Transfusion
- ClinicalTrials.gov ID
- NCT00810810
- Acronym / sponsor ID
- 29792
- Conditions
- Blood Component Transfusion
- Keywords
- Blood Component Transfusion, Leukoreduction, HLA antibody, Immunosuppression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 287 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Bloodworks
- Study start
- Jul 2006
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 18 Dec 2008 (estimated)
- Results
- Posted 29 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Biological: Standard blood componentsBlood components with no additional treatment |
| 2 | Experimental | Biological: Leukoreduced blood componentsBlood components leukoreduced |
| 3 | Experimental | Biological: Leukoreduced and irradiatedBlood components leukoreduced and irradiated |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- At least 18 year of age
- Scheduled for open heart surgery of cardiopulmonary bypass that involves: CABG, CABG with valve, aneurysm repair
- Urgent or elective surgery
Key exclusion criteria (7 listed)
- Scheduled for open heart surgery of cardiopulmonary bypass that involves: placement of a ventricular assist device, cardiac transplantation, aortic dissection repair
- Emergent surgery
- participation in other clinical research studies within 30 days of randomization.
- Immunosuppressive treatment.
- Refuse blood transfusion
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 |
|---|---|---|
| Standard blood componentsTransfusion, if ordered by physician, with unfiltered red blood cells and apheresis platelets | Biological | 1 |
| Leukoreduced blood componentsTransfusion, if ordered by a physician, of leukoreduced red blood cells and apheresis platelets | Biological | 2 |
| Leukoreduced and irradiatedTransfusion, if ordered by physician, of gamma irradiated leukoreduced red blood cells and gamma irradiated apheresis platelets | Biological | 3 |
Primary outcome
Number of Participants With Changes in the Production of Antibody to HLA Antigens
Time frame: 0 to 5 weeks after surgery
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.
1 secondary outcome
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
Time frame: 0 to 5 weeks after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31608454Nelson 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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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.
Karen Nelson, PhD principal investigator
Bloodworks
Gabriel Aldea, MD principal investigator
University of Washington
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Standard blood components, Leukoreduced blood components and Leukoreduced and irradiated in people with Blood Component Transfusion, run by University of Washington at 2 sites 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 3 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: finished, as of the sponsor's last update on 26 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 29 Nov 2017). 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?
Number of Participants With Changes in the Production of Antibody to HLA Antigens (time frame: 0 to 5 weeks after surgery). 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 NCT00810810, 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 26 Dec 2017.