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

Diabetes Mellitus, Type 2 Clinical Trial

— APPEASED  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05105919
• Other study ID #: ICM 2021-2919
• Status: Recruiting
• Phase: Early Phase 1
• Start date: August 26, 2021
• Est. completion date: July 1, 2024

Study information

• Verified date: March 2024
• Source: Montreal Heart Institute
• Contact: Guillaume Marquis Gravel, MD, MSc
• Phone: 514-376-3330
• Email: guillaume.marquis.gravel[@]umontreal.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: July 1, 2024
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

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.

Locations

Country	Name	City	State
Canada	Montreal Heart Institute	Montréal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Montreal Heart Institute	Institut de Recherches Cliniques de Montreal

Country where clinical trial is conducted

Canada, 

References & Publications (4)

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, Pe — View 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):60 — View 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. — View 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 Se — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	7 days.
Secondary	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.	7 days.
Secondary	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).	7 days.