Aspirin Resistance in Trinidad. (ART)

Aspirin Resistance in Trinidad: The ART Pilot Study.

Aspirin's beneficial effect is mediated via the inhibition of arachidonic acid (AA) activation of platelets. It is detected by demonstrating a decrease in platelet function and/or a decrease in prostaglandin metabolites. Besides inhibiting the formation of thromboxane A2 from arachidonic acid, Aspirin has a host of platelet-independent effects that complement its platelet-inhibitory effects.

The phenomenon of "Aspirin resistance" is based on the observation of clinical events in some patients taking Aspirin and/or a diminished platelet aggregation inhibitory response to Aspirin therapy. It has been suggested that many individuals taking Aspirin have become resistant to this drug. Unfortunately, laboratory assays used to monitor the efficacy of Aspirin are far from accurate, and the results are not reproducible. Multiple studies demonstrate non-compliance using repeat testing for platelet inhibition in patients with an initial inadequate response to Aspirin. When the test is repeated under the condition that the ingestion of the test Aspirin is assured, the patients' platelets are inhibited. Patients with an inadequate Aspirin response have an increased likelihood of subsequent vascular events.

Study Overview

• Status: Recruiting
• Conditions: Platelet Dysfunction Due to Drugs
• Intervention / Treatment: Drug: Aspirin 81Mg Ec Tab

Detailed Description

Aspirin is a wonder drug used for over 100 years for its analgesic and antipyretic effects. It is an inexpensive, readily available medication that reduces the risk of subsequent vascular disease by about 25% in patients with known occlusive vascular disease. For the past three decades, it has increasingly been used to prevent primary and secondary cardiovascular events.

Aspirin's beneficial effect is mediated via the inhibition of arachidonic acid (AA) activation of platelets. It is detected by demonstrating a decrease in platelet function and/or a decrease in prostaglandin metabolites. Besides inhibiting the formation of thromboxane A2 from arachidonic acid, Aspirin has a host of platelet-independent effects that complement its platelet-inhibitory effects.

The phenomenon of "Aspirin resistance" is based on the observation of clinical events in some patients taking Aspirin and/or a diminished platelet aggregation inhibitory response to Aspirin therapy. It has been suggested that many individuals taking Aspirin have become resistant to this drug. Unfortunately, laboratory assays used to monitor the efficacy of Aspirin are far from accurate, and the results are not reproducible. Multiple studies demonstrate non-compliance using repeat testing for platelet inhibition in patients with an initial inadequate response to Aspirin. When the test is repeated under the condition that the ingestion of the test Aspirin is assured, the patients' platelets are inhibited. Patients with an inadequate Aspirin response have an increased likelihood of subsequent vascular events.

The POINT pilot study introduced the preliminary observation that the estimated prevalence of HPR is considerably higher within the heterogeneous population in Trinidad at 50% compared with predominantly Caucasian studies. Furthermore, the HPR is significantly higher in South Asians (Indo-Trinidadians) (>60% of patients), which has severe clinical repercussions considering the cardiovascular disease pandemic. Clopidogrel may not be a satisfactory or optimal antiplatelet agent in this subgroup. Therefore, another more potent antiplatelet, such as ticagrelor, should be used instead.

Patients generally displayed a limited level of cardiovascular medication adherence, which is likely to translate into a higher rate of cardiovascular events with their potentially devastating sequelae.

We postulate that there is a high level of Aspirin resistance in Trinidad and Tobago.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Naveen A Seecheran, MBBS, MSc; Phone Number: 00000 1-868-753-7686; Email: naveen.seecheran@sta.uwi.edu

Study Locations

• Trinidad and Tobago
  • North
    • Saint Augustine, North, Trinidad and Tobago, 00000
      • Recruiting
      • The University of the West Indies
      • Contact: Naveen Seecheran, MBBS (MD), MSc, FACC, FESC; Phone Number: 868-753-7686; Email: nseecheran@gmail.com
      • Contact: Penelope McCallum, MBBS; Phone Number: 868-715-9811; Email: penmc1022@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. between 18 and 74 years of age,
2. healthy with no overt medical conditions,
3. not on any physician-prescribed medications or complementary/alternative therapies,

Exclusion Criteria:

1. presence of active internal bleeding or history of bleeding diathesis or clinical findings associated with an increased risk of bleeding,
2. history of ischemic or hemorrhagic stroke, transient ischemic attack, intracranial neoplasm, arteriovenous malformation, or aneurysm,
3. clinical and/or hemodynamic instability,
4. within 1 month of placement of a bare metal stent,
5. within 30 days of coronary artery bypass graft surgery or PCI without a stent placed,
6. planned coronary revascularization,
7. treatment with fibrin-specific fibrinolytic therapy <24 h or non-fibrin-specific fibrinolytic therapy <48 h,
8. use of an oral anticoagulation agent or international normalized ratio >1.5,
9. body weight <60 kg,
10. age >75 years,
11. hemoglobin <10 g/dL,
12. platelet count <100×106/μL,
13. creatinine >2 mg/dL,
14. hepatic enzymes >2.5 times the upper limit of normal,
15. pregnancy and/or lactation,
16. the patient is on any other antithrombotic therapies such as ticagrelor, dabigatran, rivaroxaban and apixaban

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aspirin Arm; Healthy patients will then undergo at least a 2-week course of 81mg of Bayer Aspirin per oral daily, followed by platelet function testing. The patients will then undergo a washout period of 2 weeks, followed by another 2-week course of 81mg Vazalore Aspirin per oral daily, followed by a second round of platelet function testing.	Drug: Aspirin 81Mg Ec Tab; Healthy patients will then undergo at least a 2-week course of 81mg of Bayer Aspirin per oral daily, followed by platelet function testing. The patients will then undergo a washout period of 2 weeks, followed by another 2-week course of 81mg Vazalore Aspirin per oral daily, followed by a second round of platelet function testing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aspirin Resistance Unit	VerifyNow Aspirin assay is a qualitative test to aid in detecting platelet dysfunction due to Aspirin ingestion in whole blood for the point-of-care or laboratory setting. The assay incorporates the agonist arachidonic acid to activate platelets, and it measures platelet function based on the ability of activated platelets to bind to fibrinogen. Fibrinogen-coated microparticles aggregate in whole blood in proportion to the number of activated platelet GP IIb/IIIa receptors. If Aspirin has produced the expected antiplatelet effect, such aggregation will be reduced. The VerifyNow Aspirin assay reports the extent of platelet aggregation as Aspirin reaction units (ARUs). Given an ARU range of 350-700, ARU values less than 550 are consistent with Aspirin-induced inhibition of platelet function. In contrast, values greater than or equal to 550 ARUs are not compatible with Aspirin-induced inhibition.	2-weeks

Collaborators and Investigators

• Sponsor: The University of The West Indies

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2024
• Primary Completion (Estimated): December 15, 2024
• Study Completion (Estimated): December 15, 2024

Study Registration Dates

• First Submitted: January 18, 2024
• First Submitted That Met QC Criteria: January 18, 2024
• First Posted (Actual): January 29, 2024

Study Record Updates

• Last Update Posted (Actual): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Aspirin
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; 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; Aspirin
• Other Study ID Numbers: CEC1153/06/19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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