Assessing Pharmacokinetics and Pharmacodynamics of Daily Enteric-coated Aspirin in Patients With StablE Diabetes

Early Phase 1Active Not RecruitingNCT05105919

Montreal Heart Institute50 enrolled

Overview

This phase 1 study will include patients suffering from type 2 diabetes mellitus and will study their response to enteric coated aspirin at a dose of 80 mg per day for a 7-day period. The aims are to determine the feasibility of a phase 2 larger scale trial, and to characterize the prevalence of incomplete platelet inhibition after exposure to EC aspirin at doses of 80 mg once daily. Platelet function will be assessed at baseline and a day 7.

APPEASED is a phase 1 open-label single arm pilot trial, aiming to determine the feasibility of a larger confirmatory randomized trial, and to characterize the prevalence of incomplete platelet inhibition after exposure to EC aspirin at doses of 80 mg once daily in patients with type 2 diabetes. The primary endpoint will be incomplete platelet aggregation in response to arachidonic acid at a concentration of 1mM, measured by LTA (Light Transmission Agregometry). For every platelet function assessment, serum salicylate concentration will also be measured. Upon the screening visit (day 0), blood will be drawn and baseline platelet function will be assessed. A 7 day supply of aspirin will be given to participants meeting the eligibility criteria. Participants will be instructed to take 1 dose of 80 mg of enteric coated aspirin per day at the same time every day. Upon day 7, participants will return for a second visit before the intake of their daily aspirin, and therefore 24 hours after the previous dose of aspirin was taken. Blood will be drawn and platelet function will be assessed in the same manner as described previously. Participants will then take their final dose of aspirin under supervision, and a final blood sample will be collected and platelet function will be assessed two hours later.

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Diabetes Mellitus, Type 2

Interventions

Aspirin 80 mg EC TabDRUG

Participants will receive a 7 day supply of Aspirin 80 mg EC Tab and will be instructed to take the drug at the same time every day for 7 days.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥ 18 years; 2. Participant must be naïve to aspirin, defined as absence of chronic treatment with aspirin within the previous 3 months, and of any aspirin use within the previous 2 weeks; 3. Type 2 diabetes, based on at least one of the following criteria: (5) * Chronic treatment with oral antihyperglycemic agents or insulin therapy; * Fasting Plasma Glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L) (fasting is defined as no caloric intake for at least 8h); * 2-h Plasma Glucose (2h-PG) ≥200 mg/dL (11.1 mmol/L) during the oral glucose tolerance test (OGTT); * A1C ≥ 6.5% (48 mmol/mol); 4. Willing to attend all study visits. Exclusion Criteria: 1. Definitive indication for aspirin, including any evidence of atherosclerotic disease, previous or current; 2. Known hypersensitivity to aspirin; 3. High-risk GI bleeding features, such as known H. pylori infection, past or present ulcer, history of bleeding from the GI tract; 4. Bleeding diathesis; 5. History of hematological malignancy or myelodysplasia; 6. Platelet count or hemoglobin levels outside of the normal reference range; 7. Planned major surgical procedure within 30 days of enrolment; 8. Chronic inflammatory disease requiring regular anti-inflammatory treatment; 9. Chronic treatment with an oral anticoagulant, an antiplatelet agent, NSAIDs or systemic steroids; 10. Active cancer; 11. Pregnant or lactating women.

Locations (1)

Montreal Heart Institute

Montreal, Quebec, Canada

Outcomes

Primary Outcomes

Incomplete platelet aggregation inhibition by aspirin at 7 days.

Incomplete platelet aggregation inhibition will be defined as ≥ 20% of residual platelet aggregation in response to arachidonic acid at a concentration of 1mM, measured by LTA (Light Transmission Aggregometry).

Time frame: 7 days.

Secondary Outcomes

Serum levels of thromboxane B2

Serum levels of thromboxane B2, measured by immunoassay \> 3.1 ng/ml will be considered as evidence of recovery of platelet function.

Time frame: 7 days.

Platelet aggregation response to various agonists

Platelet reactivity to various agonists such as ADP (Adenosine Diphosphate), TRAP (Thrombin receptor activating peptide), epinephrine and collagen will be assessed by LTA (Light Transmission Agregometry).

Time frame: 7 days.

Data from ClinicalTrials.gov

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