Clinical trial NCT05105919: Assessing Pharmacokinetics and Pharmacodynamics of Daily Enteric-coated Aspirin in Patients With StablE Diabetes
Official title: Assessing Pharmacokinetics and Pharmacodynamics of Daily Enteric-coated Aspirin in Patients With StablE Diabetes: APPEASED Study Phase 1
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Diabetes Mellitus, Type 2
Keywords: Diabetes
Aspirin
Acetylsalicylic acid
Pharmacodynamics
Lead sponsor: Montreal Heart Institute
Sponsor class: OTHER
Collaborators: name: Institut de Recherches Cliniques de Montreal
First posted: 2021-11-03
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: OTHER

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incomplete platelet aggregation inhibition by aspirin at 7 days.
timeFrame: 7 days.
Secondary outcomes:
measure: Serum levels of thromboxane B2
timeFrame: 7 days.
measure: Platelet aggregation response to various agonists
timeFrame: 7 days.
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Montreal Heart Institute
state: Quebec
Study officials:
affiliation: Montreal Heart Institute
name: Guillaume Marquis-Gravel, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Marquis-Gravel G, Roe MT, Harrington RA, Munoz D, Hernandez AF, Jones WS. Revisiting the Role of Aspirin for the Primary Prevention of Cardiovascular Disease. Circulation. 2019 Sep 24;140(13):1115-1124. doi: 10.1161/CIRCULATIONAHA.119.040205. Epub 2019 Sep 23.
citation: ASCEND Study Collaborative Group; Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J, Murphy K, Aung T, Haynes R, Cox J, Murawska A, Young A, Lay M, Chen F, Sammons E, Waters E, Adler A, Bodansky J, Farmer A, McPherson R, Neil A, Simpson D, Peto R, Baigent C, Collins R, Parish S, Armitage J. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med. 2018 Oct 18;379(16):1529-1539. doi: 10.1056/NEJMoa1804988. Epub 2018 Aug 26.
citation: Lordkipanidze M, Pharand C, Schampaert E, Palisaitis DA, Diodati JG. Heterogeneity in platelet cyclooxygenase inhibition by aspirin in coronary artery disease. Int J Cardiol. 2011 Jul 1;150(1):39-44. doi: 10.1016/j.ijcard.2010.02.025. Epub 2010 Mar 7.
citation: Bhatt DL, Grosser T, Dong JF, Logan D, Jeske W, Angiolillo DJ, Frelinger AL 3rd, Lei L, Liang J, Moore JE, Cryer B, Marathi U. Enteric Coating and Aspirin Nonresponsiveness in Patients With Type 2 Diabetes Mellitus. J Am Coll Cardiol. 2017 Feb 14;69(6):603-612. doi: 10.1016/j.jacc.2016.11.050. Epub 2017 Jan 11.