Apixaban + DAPT in Lowering Platelet Reactivity and Thrombin Generation (SEARCH)

Investigating Synergistic Effects of Apixaban With Dual Anti-Platelet Therapy (DAPT) in Lowering Platelet Reactivity and Thrombin Generation

Investigating Synergistic Effects of Apixaban with Dual Anti-Platelet Therapy (DAPT) in Lowering Platelet Reactivity and Thrombin Generation

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Diagnostic test: Flow Cytrometry; Thrombin Generation Assay

Detailed Description

Combination anti-platelet therapies particularly those combining aspirin with a P2Y12 antagonist (DAPT) are regarded as the current standard of care therapy for patients with Acute Coronary Syndrome (ACS). As thrombin potently induces platelet dense granular release and causes secondary adenosine 5'-diphosphate (ADP)-mediated P2Y12 receptor activation, apixaban via inhibition of thrombin generation may exhibit synergistic activity with direct P2Y12 receptor blockers such as clopidogrel or ticagrelor. The results from the study will provide a clearer understanding of how these antithrombotic agents work in combination and how the anti-Xa, apixaban, may reduce the contribution of thrombin and general platelet reactivity when used alone and in combination with antiplatelet agents. This study does NOT involve administration of medication to subjects. Experiments will be performed on donated blood samples from participants.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38112
      • CirQuest Labs, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 72 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

30 subjects with ACS diagnosis and dual anti-platelet therapy requirements and 10 healthy subjects; no restrictions on gender, race or ethnicity; ages 18-74, non-childbearing potential for females.

Description

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures (i.e., venipuncture).
2. Male or female at least 18 years of age but equal to or less than 75 years of age.
3. Females must be post-menopausal for at least one year or surgically sterile for at least 6 months.

4. For ACS Subjects:

   1. Documented prior history of ACS within the past 12 months.
   2. Currently prescribed a DAPT medication regimen of aspirin (81mg) plus a P2Y12 inhibitor, clopidogrel or ticagrelor, and none of the excluded medications listed in Exclusion Criteria #4.
   3. Have taken DAPT medication for at least 7 days as prescribed prior to blood collection.

5. For Healthy Subjects:

   1. Currently not prescribed and/or taking any of the excluded medications listed in Exclusion Criteria #4.

Exclusion Criteria:

1. Male or female less than 18 or greater than 75 years of age.
2. No prior history of ACS within 12 months (unless Healthy Subject)
3. Pregnancy

4. Currently prescribed and/or taking any of the following medications:

   Within the last 1 month:

   • PAR-1 antagonist (vorapaxar/Zontivity®)
   • Coumadin®
   • Heparin including low molecular weight heparin (enoxaparin/Lovenox®)
   • Factor Xa inhibitors (rivaroxaban/Xarelto®, apixaban/Eliquis®, edoxaban/Savaysa®, betrixaban/Bevyxxa®)
   • Direct thrombin inhibitors (hirudin, bivalirudin/Angiomax®, dabigatran/Pradaxa®)

   Within last 10 days:

   • Glycoprotein IIb/IIIa inhibitors (Eptifibatide/Integrilin®, Tirofiban/Aggrastat®, Abciximab/ReoPro®)
   • Acetylsalicylic Acid/Aspirin products (Alka-Seltzer®, Goody Powder®, BC Powder®, Pepto Bismol®, Aggrenox®) (except aspirin as prescribed for DAPT participants)

   Within last 3 days:

   • Phosphodiesterase inhibitors (cilostazol/Pletal®)
   • Adenosine reuptake inhibitors (dipyridamole/Persantine®)
   • NSAIDs
   • Decongestants
   • Antidepressants or Anti-anxiety medications:
   • Selective Serotonin Reuptake Inhibitors (SSRI) (fluoxetine/Prozac®, sertraline/Zoloft®, paroxetine/Paxil®)
   • Selective Norepinephrine Reuptake Inhibitors (SNRI) (venlafaxine/Effexor® or duloxetine/Cymbalta®)
5. Diagnosed with or possessing significant renal dysfunction as defined by the physician/investigator.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ACS using clopidogrel + aspirin; Apixaban combined with blood specimens (in vitro) from Acute Coronary Syndrome participants prescribed a regimen of DAPT in the form of clopidogrel + aspirin	Diagnostic test: Flow Cytrometry; Thrombin Generation Assay; Apixaban combined with blood specimens (in vitro) of study participants
ACS using ticagrelor + aspirin; Apixaban combined with blood specimens (in vitro) from Acute Coronary Syndrome participants prescribed a regimen of DAPT in the form of ticagrelor + aspirin	Diagnostic test: Flow Cytrometry; Thrombin Generation Assay; Apixaban combined with blood specimens (in vitro) of study participants
Healthy Donors; Apixaban combined with blood specimens (in vitro) from healthy participants	Diagnostic test: Flow Cytrometry; Thrombin Generation Assay; Apixaban combined with blood specimens (in vitro) of study participants

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Synergistic effects of in-vitro apixaban	Synergistic effects of in-vitro apixaban with antiplatelet agents in inhibiting platelet reactivity and thrombin generation	1 day

Collaborators and Investigators

• Sponsor: CirQuest Labs, LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2018
• Primary Completion (Actual): November 8, 2019
• Study Completion (Actual): November 8, 2019

Study Registration Dates

• First Submitted: July 11, 2018
• First Submitted That Met QC Criteria: November 16, 2018
• First Posted (Actual): November 20, 2018

Study Record Updates

• Last Update Posted (Actual): January 23, 2020
• Last Update Submitted That Met QC Criteria: January 22, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Dual Anti-Platelet Therapy
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Acute Coronary Syndrome; Hemostatics; Coagulants; Thrombin
• Other Study ID Numbers: CV185-511 / CQ-15-10-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes