Reversal of Dual Antiplatelet Therapy With Cold Stored Platelets

Bleeding Clinical Trial

— R-DAPT  

Official title:

Reversal of Dual Antiplatelet Therapy With Cold Stored Platelets

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03787927
• Other study ID #: 2018-02
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: December 3, 2018
• Est. completion date: December 3, 2021

Study information

• Verified date: July 2020
• Source: Bloodworks
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: December 3, 2021
• Est. primary completion date: December 3, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

Inclusion Criteria:

The subject is in good health, is taking no excluded medications and meets platelet donor suitability requirements aimed at assuring donor safety.

1. Subject self-reports that he or she feels well and healthy

2. Subjects must be 18-59 years old, of either sex

3. Temperature: less than or equal to 99.5 F

4. Resting blood pressure: systolic less than or equal to 180 mmHg, diastolic less than or equal to100 mmHg

5. Resting heart rate: 40 to 100 beats per minute

6. Weight: greater than or equal to110 pounds,

7. Hematocrit: greater than or equal to 35 percent for females, greater than or equal to 38 percent for males, but not greater than 55 percent

8. Platelet count able to achieve target platelet yield per apheresis machine configuration parameters

9. Subjects must be able to read, understand and sign the informed consent document and commit to the study follow-up schedule. The ability to read and speak English is required for participation.

10. Subject must agree to avoid taking any aspirin or aspirin-containing drugs (e.g., Alka-Seltzer, Bufferin, Excedrin) or NSAIDs (e.g.,Feldene, Motrin, Aleve, Advil) or other drugs known to affect platelet function throughout their study participation.

11. Subjects must agree to avoid calcium channel blockers such as amlodipine (Norvasc), felodipine, and verapamil (Verelan, Calan) and proton pump inhibitors (PPIs) such as omeprazole (Prilosec), lansoprazole (Prevacid), esomeprazole (Nexium) and pantoprazole (Protonix) until all study blood draws are concluded. These classes of drugs may interfere with the action of clopidogrel and diminish its antiplatelet effect.

12. Subjects must have "good veins" for apheresis platelet collection and drawing blood samples.

13. Women of child bearing potential must agree to use an effective method of contraception during the course of the study. The following methods of contraception will be considered 'effective' when self-reported by subject; abstinence, intrauterine contraception devices, hormonal methods, barrier methods or history of sterilization.

14. Subject has phone and e-mail for contact and notification, and is able to come to the research site for approximately 9 visits over up to approximately 64 days.

Exclusion Criteria:

Healthy subjects will be excluded from the study for any of the following reasons:

1. Active acute infection or suspected active infection, temperature above 100 F or taking antibiotic

2. Active immune/inflammatory condition (e.g. gout, systemic lupus erythematosus, allograft rejection)

3. History of heart disease, including endorsement of shortness of breath with mild exertion (at the discretion of the PI).

4. History of significant liver, kidney, GI, blood, endocrine/metabolic, autoimmune or pulmonary disease, untreated hypertension and or metabolic syndrome (at the discretion of the PI).

5. Diabetes Mellitus

6. Cancer of any kind (exceptions being basal or squamous cell cancers of the skin), under treatment or resolved

7. History of bleeding events, family history of bleeding events, or known genetic disorder with bleeding diathesis

8. A family history of venous or arterial thrombosis before the age of 50 in first degree relatives

9. A personal history of DVT, venous or arterial thrombosis, blood clots or stroke

10. History of having been prescribed clopidogrel (Plavix), ticlopidine (Ticlid) or Ticagrelor (Brilinta).

11. Subject has taken any aspirin or aspirin-containing drugs (e.g., Alka-Seltzer, Bufferin, Excedrin) or NSAIDs (e.g.,Feldene, Motrin, Aleve, Advil) or other drugs known to affect platelet function within 14 days prior to screening.

12. Chronic NSAID therapy

13. Chronic steroid therapy

14. Known allergy to aspirin or clopidogrel

15. Subjects who are taking, or have taken within 14 days any of the following class of drugs protone pump inhibitors (PPIs) such as omeprazole, pantoprazole, lansoprazole, esomeprazole lipid lowering drugs/statins anticoagulants ACE-inhibitors phenytoine tolbutamide calcium channel blockers such as amlodipine, felodipine, verapamil

16. Current drug or alcohol dependence by subject's declaration.

17. Currently pregnant or nursing as assessed during interview. A urine pregnancy test prior to apheresis is required for women of childbearing potential.

18. Subject plans to participate in contact sports during study/observational period such as boxing, rugby, American football, soccer, or other risky recreational hobbies at the discretion of the investigator.

19. Unwilling or unable to comply with the protocol in the opinion of the investigator.

20. Participation in an experimental drug/device study within the past 30 days (other than this study). Subjects who have received an infusion on this study may not be re-enrolled.

21. Average initial (only for the first PFT) aggregation responses to ADP less than or equal to 60% by aggregometry platelet function testing.

22. Other unspecified reasons that, in the opinion of the Investigator, make the subject unsuitable for enrollment.

Related Conditions & MeSH terms

• Bleeding
• Blood Platelet Disorders
• Platelet Dysfunction
• Platelet Dysfunction Due to Drugs

Intervention

Drug:
• Autologous Platelet Transfusion (room-temperature-stored)
The participant will receive an autologous platelet transfusion of their room-temperature-stored platelets after 5 days of storage.
• Autologous Platelet Transfusion (cold-stored 5 days)
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)
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)
The participant will receive an autologous platelet transfusion of their cold-stored platelets after 15 days of storage.
• Aspirin
Aspirin (325mg) will be administered the day before every transfusion.
• Clopidogrel
Clopidogrel (600mg) will be administered the day before every transfusion.

Locations

Country	Name	City	State
United States	Bloodworks Northwest Research Institute	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Bloodworks	National Blood Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Verify Now (PRU): aIIbß3 (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
Primary	Verify Now: aIIbß3 (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
Primary	PAC-1: aIIbß3 (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
Secondary	LTA: aIIbß3 (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
Secondary	P-Selectin:aIIbß3 (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
Secondary	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
Secondary	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
Secondary	Platelet unit blood gas: changes during storage	during storage of the units	day of collection, day of transfusion
Secondary	Platelet unit Annexin V: changes during storage		day of collection, day of transfusion
Secondary	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
Secondary	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