A Pharmacodynamic Comparison of Prasugrel (LY640315) Versus High Dose Clopidogrel in Subjects With Type 2 Diabetes Mellitus and Coronary Artery Disease.
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 35
- Locations
- 1
- Primary Endpoint
- Inhibition of Platelet Aggregation (IPA) 4 Hours After Loading Dose Assessed by Accumetrics VerifyNow™ P2Y12 Assay
Study Overview
Brief Summary
This trial is designed as a phase 2 randomized, double-blind double dummy, active comparator controlled, two-period two-arm crossover study to enroll 40 patients across multiple centers. The study will compare platelet function following a prasugrel loading dose and 1 week of prasugrel maintenance therapy with high-dose clopidogrel loading dose and 1 week of high-dose clopidogrel maintenance therapy in patients with drug treated type 2 diabetes mellitus who have coronary artery disease. Various assays of platelet function will be used in this study. Platelet function will be studied using the following assays: Accumetrics VerifyNowTM P2Y12, Light Transmittance Aggregometry (LTA), Vasodilator-associated stimulated phosphoprotein (VASP), and Thromboelastography (TEG)-platelet mapping.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 74 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Type 2 Diabetes Mellitus and on oral or parenteral hypoglycemic therapy for at least 1 month.
- •History of Coronary Artery Disease with or without other types of vascular disease (such as peripheral vascular disease).
- •Taking Aspirin 75-325 mg/day for at least 1 week prior to randomization.
- •Between the ages of 18-74 years old.
- •If a woman of child bearing age, must not be pregnant and must agree to use reliable method of birth control during the duration of the study.
Exclusion Criteria
- •Thienopyridine therapy within 30 days or have a defined need for thienopyridine treatment.
- •Coronary Artery Bypass Graft (CABG) or Percutaneous Coronary Intervention (PCI) with no stent placed within 30 days.
- •Planned coronary revascularization
- •Hemoglobin A1c (HbA1c) > or equal to 10 mg/dL within the last 3 months.
- •Received fibrolytic therapy <24 hours prior to randomization.
- •Received non-fibrin-specific fibrinolytic therapy <48 hours prior to randomization.
- •At risk of bleeding.
- •History of ischemic stroke, transient ischemic attack (TIA), intercranial neoplasm, arteriovenous malformation, or aneurysm.
- •Body weight <60 kilograms (kg).
- •International Normalized Ratio (INR) >1.5, platelet count <100,000/mm3, or anemia (hemoglobin <10 gm/dL) within 1 week of study entry.
- •Are receiving or will receive oral anticoagulation or antiplatelet treatment therapy.
- •Are being treated with daily non-steroidal anti-inflammatory drugs (NSAIDS).
- •Are pregnant, breast-feeding or plan to become pregnant.
Arms & Interventions
Prasugrel
Oral prasugrel 60-mg loading dose, followed by 6 to 9 days of prasugrel 10-mg/day tablet maintenance dose.
Intervention: prasugrel (Drug)
Clopidogrel
Oral clopidogrel 600-mg loading dose, followed by 6 to 9 days of clopidogrel 150-mg/day tablet maintenance dose.
Intervention: Clopidogrel (Drug)
Outcomes
Primary Outcomes
Inhibition of Platelet Aggregation (IPA) 4 Hours After Loading Dose Assessed by Accumetrics VerifyNow™ P2Y12 Assay
Time Frame: 4 hours after loading dose
The inhibition of platelet aggregation 4 hours after the loading dose was administered was assessed using the Accumetrics VerifyNow™ P2Y12 assay. Percentage inhibition, as reported by VerifyNow™ P2Y12, was calculated from P2Y12 Reaction Unit (PRU) (rate and extent of adenosine diphosphate \[ADP\]-stimulated platelet aggregation) and BASE (estimate of baseline platelet reactivity independent of P2Y12 receptor inhibition \[reference values\]: rate and extent of Thrombin Receptor-Activated Peptide-stimulated platelet aggregation) values as follows: Percentage (%) inhibition = (1-PRU/BASE) x 100.
Secondary Outcomes
- Inhibition of Platelet Aggregation at 1- and 24-Hours After Loading Dose (LD) and 24-Hours After Last Maintenance Dose (LMD) Assessed by Accumetrics VerifyNow™ P2Y12 Assay(1 hour and 24 hours after the loading dose (LD) and 24 hours after the last maintenance dose (LMD))
- Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA)(Baseline, 1 Hour, 4 Hours, and 24 Hours after loading dose, and 24 Hours after last maintenance dose)
- Platelet Reactivity Index (PRI)(Baseline, 1 Hour, 4 Hours, and 24 Hours after loading dose, and 24 Hours after last maintenance dose)
- Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate(Baseline, 1 Hour, 4 Hours, and 24 Hours after loading dose, and 24 Hours after last maintenance dose)