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| Name | Class |
|---|---|
| National Blood Foundation | UNKNOWN |
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This study aims to determine whether cold-stored platelets (CSP) are equally, more effective, or uniquely effective at reversing the effect of dual antiplatelet therapy in healthy human subjects compared to room-temperature-stored platelets (RTP). The investigators plan to enroll healthy human subjects without risk factors for bleeding to achieve 60 complete data sets. Each subject will donate two apheresis platelet units. One platelet unit will be stored in the cold (CSP) and one platelet unit will be stored at room temperature (RTP). Subjects will be given dual anti-platelet therapy (aspirin and clopidogrel) prior to autologous transfusion of each unit. Platelet function testing will be performed before and after transfusion to measure reversal of the antiplatelet drugs.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 5 day CSP, then 5 day RTP | Other | Participants will first complete collection and transfusion of 5 day autologous CSP (cold-stored platelet). Then they will complete collection and transfusion of 5 day autologous RTP (room-temperature-stored platelets). The day before each transfusion, Aspirin (325mg) and Clopidogrel (600mg) will be administered. The first 20 participants who complete the study will be randomized to this arm or '5 day RTP, then 5 day CSP.' Interventions include: Aspirin, Clopidogrel, Autologous Platelet Transfusion (cold-stored 5 days), Autologous Platelet Transfusion (room-temperature-stored 5 days) |
|
| 5 day RTP, then 5 day CSP | Other | Participants will first complete collection and transfusion of 5 day autologous RTP (room-temperature-stored platelets). Then they will complete collection and transfusion of 5 day autologous CSP (cold-stored platelets). The day before each transfusion, Aspirin (325mg) and Clopidogrel (600mg) will be administered. The first 20 participants who complete the study will be randomized to this arm or '5 day CSP, then 5 day RTP.' Interventions include: Aspirin, Clopidogrel, Autologous Platelet Transfusion (cold-stored 5 days), Autologous Platelet Transfusion (room-temperature-stored 5 days) |
|
| 5 day RTP, then 10 day CSP | Other | Participants will first complete collection and transfusion of 5 day autologous RTP (room-temperature-stored platelets). Then they will complete collection and transfusion of 10 day autologous CSP (cold-stored platelets).The day before each transfusion, Aspirin (325mg) and Clopidogrel (600mg) will be administered. After the first 20 complete data sets are obtained from subjects, the next 20 complete data sets will be obtained (if progression to this arm is indicated) by randomizing subjects between '5 day RTP, then 10 day CSP' and '10 day CSP, then 5 day RSP.' Interventions include: Aspirin, Clopidogrel, Autologous Platelet Transfusion (cold-stored 10 days), Autologous Platelet Transfusion (room-temperature-stored 5 days) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Autologous Platelet Transfusion (room-temperature-stored) | Drug | The participant will receive an autologous platelet transfusion of their room-temperature-stored platelets after 5 days of storage. |
| Measure | Description | Time Frame |
|---|---|---|
| Verify Now (PRU): αIIbβ3 (GPIIb-IIIa) integrin activation changes between DAPT loaded pre-transfusion, 1 hour post-transfusion, 4 hour post-transfusion, 24 hour post-transfusion, baseline | Measured by Verify Now (PRU) | Measured at baseline, pre-transfusion (after administration of dual anti-platelet therapy), 1 hour post-transfusion, 24 hour post-transfusion |
| Verify Now: αIIbβ3 (GPIIb-IIIa) integrin activation changes between DAPT loaded pre-transfusion, 1 hour post-transfusion, 4 hour post-transfusion, 24 hour post-transfusion, baseline | Measured by Verify Now (ARU) | Measured at baseline, pre-transfusion (after administration of dual anti-platelet therapy), 1 hour post-transfusion, 24 hour post-transfusion |
| PAC-1: αIIbβ3 (GPIIb-IIIa) integrin activation changes between DAPT loaded pre-transfusion, 1 hour post-transfusion, 4 hour post-transfusion, 24 hour post-transfusion, baseline | Measured by PAC-1 antibody binding by flow cytometry | Measured at baseline, pre-transfusion (after administration of dual anti-platelet therapy), 1 hour post-transfusion, 4 hour post-transfusion, 24 hour post-transfusion |
| Measure | Description | Time Frame |
|---|---|---|
| LTA: αIIbβ3 (GPIIb-IIIa) integrin activation changes from DAPT loaded pre-transfusion, 1 hour post-transfusion, 4 hour post-transfusion, 24 hour post-transfusion, baseline | Light Transmittance Aggregometry | Measured at baseline, pre-transfusion (after administration of dual anti-platelet therapy), 1 hour post-transfusion, 4 hour post-transfusion, 24 hour post-transfusion |
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Inclusion Criteria:
The subject is in good health, is taking no excluded medications and meets platelet donor suitability requirements aimed at assuring donor safety.
Exclusion Criteria:
Healthy subjects will be excluded from the study for any of the following reasons:
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| Name | Affiliation | Role |
|---|---|---|
| Moritz Stolla, MD | Bloodworks Northwest | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bloodworks Northwest Research Institute | Seattle | Washington | 98102 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34478498 | Derived | Miles J, Bailey SL, Obenaus AM, Mollica MY, Usaneerungrueng C, Byrne D, Fang L, Flynn JR, Corson J, Osborne B, Houck K, Wang Y, Shen Y, Fu X, Dong JF, Sniadecki NJ, Stolla M. Storage temperature determines platelet GPVI levels and function in mice and humans. Blood Adv. 2021 Oct 12;5(19):3839-3849. doi: 10.1182/bloodadvances.2021004692. |
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| 5 day RTP, then 15 day CSP | Other | Participants will first complete collection and transfusion of 5 day autologous RTP (room-temperature-stored platelets). Then they will complete collection and transfusion of 15 day autologous CSP (cold-stored platelets). The day before each transfusion, Aspirin (325mg) and Clopidogrel (600mg) will be administered. After the first 40 complete data sets are obtained from subjects, the next 20 complete data sets will be obtained (if progression to this arm is indicated) by randomizing subjects between '5 day RTP, then 15 day CSP' and '15 day CSP, then 5 day RSP.' Interventions include: Aspirin, Clopidogrel, Autologous Platelet Transfusion (cold-stored 15 days), Autologous Platelet Transfusion (room-temperature-stored 5 days) |
|
| 10 day CSP, then 5 day RTP | Other | Participants will first complete collection and transfusion of 10 day autologous CSP (cold-stored platelet). Then they will complete collection and transfusion of 5 day autologous RTP (room-temperature-stored platelets).The day before each transfusion, Aspirin (325mg) and Clopidogrel (600mg) will be administered. After the first 20 complete data sets are obtained from subjects, the next 20 complete data sets will be obtained (if progression to this arm is indicated) by randomizing subjects between '5 day RTP, then 10 day CSP' and '10 day CSP, then 5 day RSP.' Interventions include: Aspirin, Clopidogrel, Autologous Platelet Transfusion (cold-stored 10 days), Autologous Platelet Transfusion (room-temperature-stored 5 days) |
|
| 15 day CSP, then 5 day RTP | Other | Participants will first complete collection and transfusion of 15 day autologous CSP (cold-stored platelet). Then they will complete collection and transfusion of 5 day autologous RTP (room-temperature-stored platelets). The day before each transfusion, Aspirin (325mg) and Clopidogrel (600mg) will be administered. After the first 40 complete data sets are obtained from subjects, the next 20 complete data sets will be obtained (if progression to this arm is indicated) by randomizing subjects between '5 day RTP, then 15 day CSP' and '15 day CSP, then 5 day RSP.' Interventions include: Aspirin, Clopidogrel, Autologous Platelet Transfusion (cold-stored 15 days), Autologous Platelet Transfusion (room-temperature-stored 5 days) |
|
| Autologous Platelet Transfusion (cold-stored 5 days) | Drug | The participant will receive an autologous platelet transfusion of their cold-stored platelets after 5 days of storage. |
|
| Autologous Platelet Transfusion (cold-stored 10 days) | Drug | The participant will receive an autologous platelet transfusion of their cold-stored platelets after 10 days of storage. |
|
| Autologous Platelet Transfusion (cold-stored 15 days) | Drug | The participant will receive an autologous platelet transfusion of their cold-stored platelets after 15 days of storage. |
|
| Aspirin | Drug | Aspirin (325mg) will be administered the day before every transfusion. |
|
| Clopidogrel | Drug | Clopidogrel (600mg) will be administered the day before every transfusion. |
|
| P-Selectin:αIIbβ3 (GPIIb-IIIa) integrin activation changes between DAPT loaded pre-transfusion, 1 hour post-transfusion, 4 hour post-transfusion, 24 hour post-transfusion, baseline | Measured by alpha-granule secretion (P-Selectin) by flow cytometry | Measured at baseline, pre-transfusion (after administration of dual anti-platelet therapy), 1 hour post-transfusion, 4 hour post-transfusion, 24 hour post-transfusion |
| Beeding time testing (in-vivo) changes between DAPT loaded pre-transfusion, 1 hour post-transfusion, 4 hour post-transfusion, 24 hour post-transfusion, baseline | in-vivo subject testing | Measured at baseline, pre-transfusion (after administration of dual anti-platelet therapy), 1 hour post-transfusion, 4 hour post-transfusion, 24 hour post-transfusion |
| CBC changes between DAPT loaded pre-transfusion, 1 hour post-transfusion, 4 hour post-transfusion, 24 hour post-transfusion, baseline | Measured at baseline, pre-transfusion (after administration of dual anti-platelet therapy), 1 hour post-transfusion, 4 hour post-transfusion, 24 hour post-transfusion |
| Platelet unit blood gas: changes during storage | during storage of the units | day of collection, day of transfusion |
| Platelet unit Annexin V: changes during storage | day of collection, day of transfusion |
| Thromboxane B2 ELISA changes between DAPT loaded pre-transfusion, 1 hour post-transfusion, 4 hour post-transfusion, 24 hour post-transfusion, baseline | Measured at baseline, pre-transfusion (after administration of dual anti-platelet therapy), 1 hour post-transfusion, 4 hour post-transfusion, 24 hour post-transfusion |
| Vasodilator-stimulated phosphoprotein (VASP) changes | Measured at baseline, pre-transfusion (after administration of dual anti-platelet therapy), 1 hour post-transfusion, 4 hour post-transfusion, 24 hour post-transfusion |
| ID | Term |
|---|---|
| D006470 | Hemorrhage |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D001241 | Aspirin |
| D000077144 | Clopidogrel |
| ID | Term |
|---|---|
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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