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

Sponsor

Montreal Heart Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT05105919

Collaborator

Institut de Recherches Cliniques de Montreal (Other)

Enrollment

Location

Arm

11.4

Anticipated Duration (Months)

4.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Aspirin 80 mg EC Tab	Early Phase 1

Detailed Description

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is a single arm open-label feasibility phase 1 trial. The aim of the study if to determine the number of potentially eligible participants and the monthly recruitment rate at the MHI (Montreal Heart Institute), the Centre Épic and the IRCM (Institut de recherche clinique de Montréal) as well as participants adherence to study protocol to determine feasibility of a phase 2 trial within these centers.This is a single arm open-label feasibility phase 1 trial. The aim of the study if to determine the number of potentially eligible participants and the monthly recruitment rate at the MHI (Montreal Heart Institute), the Centre Épic and the IRCM (Institut de recherche clinique de Montréal) as well as participants adherence to study protocol to determine feasibility of a phase 2 trial within these centers.

Masking:

None (Open Label)

Masking Description:

All enrolled participants will receive the same treatment.

Primary Purpose:

Other

Official Title:

Assessing Pharmacokinetics and Pharmacodynamics of Daily Enteric-coated Aspirin in Patients With StablE Diabetes: APPEASED Study Phase 1

Actual Study Start Date :

Aug 26, 2021

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Aug 8, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aspirin therapy All participants will be assigned to aspirin therapy. Participants will receive 80 mg of enteric coated aspirin per day for a 7 day period.	Drug: Aspirin 80 mg EC Tab 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.

Arm

Intervention/Treatment

Experimental: Aspirin therapy

All participants will be assigned to aspirin therapy. Participants will receive 80 mg of enteric coated aspirin per day for a 7 day period.

Drug: Aspirin 80 mg EC Tab

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.

Outcome Measures

Primary Outcome Measures

Incomplete platelet aggregation inhibition by aspirin at 7 days. [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).

Secondary Outcome Measures

Serum levels of thromboxane B2 [7 days.]
Serum levels of thromboxane B2, measured by immunoassay > 3.1 ng/ml will be considered as evidence of recovery of platelet function.
Platelet aggregation response to various agonists [7 days.]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years;
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;
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);

Willing to attend all study visits.

Exclusion Criteria:

Definitive indication for aspirin, including any evidence of atherosclerotic disease, previous or current;
Known hypersensitivity to aspirin;
High-risk GI bleeding features, such as known H. pylori infection, past or present ulcer, history of bleeding from the GI tract;
Bleeding diathesis;
History of hematological malignancy or myelodysplasia;
Platelet count or hemoglobin levels outside of the normal reference range;
Planned major surgical procedure within 30 days of enrolment;
Chronic inflammatory disease requiring regular anti-inflammatory treatment;
Chronic treatment with an oral anticoagulant, an antiplatelet agent, NSAIDs or systemic steroids;
Active cancer;
Pregnant or lactating women.