The Accuracy Of A Novel Platelet Activity Assay In Humans On Antiplatelet Agents: Pharmacodynamics And Comparison With Light Transmission Aggregometry

The purpose of this study is to test a novel diagnostic immunoassay of platelet function and compare it to the current gold standard platelet function assay by testing the response to aspirin and clopidogrel in a group of healthy volunteers and severely obese individuals and comparing the accuracy of the two tests. The secondary goals will be to evaluate the pharmacodynamic parameters of the antiplatelet agents across the two testing modalities and refine the cutoffs used for the novel assay.

Study Overview

• Status: Recruiting
• Conditions: Healthy; Platelet Activation Testing Before/After Anti-platelet Therapy
• Intervention / Treatment: Drug: Aspirin; Drug: Clopidogrel

• Study Type: Interventional
• Enrollment (Anticipated): 125
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jeffrey Zwicker, MD; Phone Number: 617-667-9920; Email: jzwicker@bidmc.harvard.edu
• Study Contact Backup: Name: Pavania Elavalakanar, MSc; Phone Number: 617-667-1903; Email: pelavala@bidmc.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Jeffrey Zwicker, MD; Phone Number: 617-667-9920; Email: jzwicker@bidmc.harvard.edu
      • Contact: Pavania Elavalakanar, MSc; Phone Number: 617-667-1903; Email: pelavala@bidmc.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject is ≥18 years of age
2. Subject is willing to participate and provide informed consent
3. Subject is considered reliable and capable of adhering to the protocol per the judgment of the Investigator
4. Groups A, B and C: BMI < 30 kg/m2; Groups D and E: BMI ≥ 35 kg/m2
5. Subjects must be age ≥ 18 years old
6. Serum Creatinine < 1.5 mg/dL
7. Platelet count ≥ 150 K/uL
8. Hematocrit ≥ 38%

Exclusion Criteria:

1. Pregnant. If female of child-bearing age, negative urinary pregnancy test required at time of enrollment. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant she should inform her treating physician immediately.
2. Established diagnosis of cirrhosis or active cancer
3. History of allergy to aspirin or clopidogrel
4. Any history of taking aspirin, antiplatelet drugs, NSAIDS, cyclooxygenase (COX)-2 inhibitors, warfarin, low-molecular weight heparin, thrombolytic agents, or other anticoagulants (such as direct thrombin inhibitors or factor X inhibitors) within 2 weeks prior to enrollment. (Refer to appendix)
5. Use of certain antibiotics, cardiovascular drugs, lipid-lowering agents, antidepressants, antihistamines, non-prescription drugs, and supplements within the past 2 weeks. (Refer to appendix)
6. Any major illness requiring hospitalization or surgery in the previous six months.
7. Personal history of gastrointestinal bleed in the last 24 months or diagnosis of peptic ulcer disease in the last 12 months
8. Lifetime personal history of hemorrhagic stroke.
9. Personal or family history of bleeding diatheses, including hemophilias, von Willebrand's disease, Bernard-Soulier syndrome, or Glanzmann thrombasthenia (unless otherwise confirmed not present in study subject)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Healthy; Low Dose Aspirin - 81mg daily for 7 days	Drug: Aspirin; Low dose aspirin in Arms A and D and High Dose Aspirin in Arm B
Experimental: Group B: Healthy; High Dose Aspirin - 325mg daily for 7 days	Drug: Aspirin; Low dose aspirin in Arms A and D and High Dose Aspirin in Arm B
Experimental: Group C: Healthy; Clopidogrel 300mg on Day 1 and 75mg daily for 6 subsequent days	Drug: Clopidogrel; Arms C and E
Experimental: Group D: Obese; Low Dose Aspirin - 81mg daily for 7 days	Drug: Aspirin; Low dose aspirin in Arms A and D and High Dose Aspirin in Arm B
Experimental: Group E: Obese; Clopidogrel 300mg on Day 1 and 75mg daily for 6 subsequent days	Drug: Clopidogrel; Arms C and E

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison at day 5 of pDrp1 Assay relative to Light Transmission Aggregometry	Sensitivity of pDrp1 assay for platelet inhibition at day 5	5 days

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2021
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: March 26, 2021
• First Submitted That Met QC Criteria: March 26, 2021
• First Posted (Actual): March 30, 2021

Study Record Updates

• Last Update Posted (Actual): April 1, 2022
• Last Update Submitted That Met QC Criteria: March 31, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Clopidogrel
• Other Study ID Numbers: 2021-P-000134

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: Yes
• Studies a U.S. FDA-regulated device product: No