Coronary Artery Disease, Diabetes Mellitus
Conditions
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.
Interventions
DRUGprasugrel
Oral prasugrel 60-mg loading dose, followed by 6-9 days of oral prasugrel 10-mg/day tablet maintenance dose.
DRUGClopidogrel
Oral clopidogrel 600-mg loading dose, followed by 6-9 days of oral clopidogrel 150-mg/day tablet maintenance dose.
Sponsors
Daiichi Sankyo
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inhibition of Platelet Aggregation (IPA) 4 Hours After Loading Dose Assessed by Accumetrics VerifyNow™ P2Y12 Assay | 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | Inhibition of platelet aggregation 1- and 24-hours after loading dose and 24-hours after last maintenance dose was administered was assessed using Accumetrics VerifyNow™ P2Y12 assay. Percentage inhibition, as reported by VerifyNow™ P2Y12, was calculated from PRU (rate and extent of 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. |
| 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 | Mean platelet aggregation (MPA) to 5 and 20 µM adenosine diphosphate (ADP) was assessed by light transmittance aggregometry (LTA). Platelet aggregation was monitored for a total of 7 minutes after addition of ADP. Maximum platelet aggregation was the maximal aggregation value achieved during the 7-minute observation period following addition of agonists. |
| Platelet Reactivity Index (PRI) | Baseline, 1 Hour, 4 Hours, and 24 Hours after loading dose, and 24 Hours after last maintenance dose | Data from the Vasodilator-associated stimulated phosphoprotein assay were reported as the platelet reactivity index (PRI) which was calculated from corrected mean fluorescence intensity (cMFI) following incubation of platelets with either prostaglandin E1 (PGE1) alone or PGE1 plus ADP: Platelet Reactivity Index (%) = \[1-(cMFI PGEI+ADP/cMFI PGEI)\] x 100. Lower PRI values indicate greater platelet P2Y12 inhibition. |
| 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 | Thromboelastography (TEG) platelet mapping (MP) maximum amplitude (MA) - Adenosine Diphosphate (ADP) millimeters (mm) at each time point. The TEG-MP MA measures strength of clot formation in whole blood. MA-ADP is the maximal amplitude resulting from fibrin and platelets not blocked by ADP-receptor inhibiting drugs. Fibrin strands in blood sample link a rotating sample cup with a stationary pin suspended by a torsion wire. The degree of platelet contribution to the MA through platelet-fibrin bonding directly influences the magnitude of pin movement and ultimately the amplitude of the tracing. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prasugrel Then Clopidogrel Prasugrel: Oral prasugrel 60-mg loading dose, followed by 6 to 9 days of prasugrel 10-mg/day tablet maintenance dose. Clopidogrel: Oral clopidogrel 600-mg loading dose, followed by 6 to 9 days of clopidogrel 150-mg/day tablet maintenance dose. | 18 |
| Clopidogrel Then Prasugrel Clopidogrel: Oral clopidogrel 600-mg loading dose, followed by 6 to 9 days of clopidogrel 150-mg/day tablet maintenance dose. Prasugrel: Oral prasugrel 60-mg loading dose, followed by 6 to 9 days of prasugrel 10-mg/day tablet maintenance dose. | 17 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 - Initial Drug | Entry Criteria Not Met | 0 | 1 |
Baseline characteristics
| Characteristic | Prasugrel Then Clopidogrel | Clopidogrel Then Prasugrel | Total |
|---|---|---|---|
| Age Continuous | 60.3 years STANDARD_DEVIATION 9.43 | 62.4 years STANDARD_DEVIATION 8.14 | 61.3 years STANDARD_DEVIATION 8.76 |
| Race/Ethnicity, Customized African | 3 participants | 4 participants | 7 participants |
| Race/Ethnicity, Customized Caucasian | 8 participants | 7 participants | 15 participants |
| Race/Ethnicity, Customized East Asian | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic | 4 participants | 4 participants | 8 participants |
| Race/Ethnicity, Customized Native American | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized West Asian | 2 participants | 1 participants | 3 participants |
| Region of Enrollment United States | 18 participants | 17 participants | 35 participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 14 Participants | 10 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 34 | 9 / 35 |
| serious Total, serious adverse events | 0 / 34 | 0 / 35 |
Outcome results
Primary
Inhibition of Platelet Aggregation (IPA) 4 Hours After Loading Dose Assessed by Accumetrics VerifyNow™ P2Y12 Assay
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.
Time frame: 4 hours after loading dose
Population: Pharmacodynamic Population, which included all randomized participants who had blood draws for IPA at 4 hours, who met compliance criteria, and who had last dose of study drug prior to the blood draw for IPA.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Prasugrel | Inhibition of Platelet Aggregation (IPA) 4 Hours After Loading Dose Assessed by Accumetrics VerifyNow™ P2Y12 Assay | Baseline | 9.4 percent inhibition | 95% Confidence Interval 10.23 |
| Prasugrel | Inhibition of Platelet Aggregation (IPA) 4 Hours After Loading Dose Assessed by Accumetrics VerifyNow™ P2Y12 Assay | 4 Hours After Loading Dose | 89.3 percent inhibition | 95% Confidence Interval 9.4 |
| Clopidogrel | Inhibition of Platelet Aggregation (IPA) 4 Hours After Loading Dose Assessed by Accumetrics VerifyNow™ P2Y12 Assay | Baseline | 9.3 percent inhibition | 95% Confidence Interval 11.46 |
| Clopidogrel | Inhibition of Platelet Aggregation (IPA) 4 Hours After Loading Dose Assessed by Accumetrics VerifyNow™ P2Y12 Assay | 4 Hours After Loading Dose | 27.7 percent inhibition | 95% Confidence Interval 23.82 |
Comparison: Null hypothesis: there is no difference between prasugrel and clopidogrel in IPA assessed by Accumetrics VerifyNow™ P2Y12 4 hours after administration of loading dose. Assuming 90% power, 2-sided alpha of 0.05, and a 17.5% difference in IPA between treatment groups with a standard deviation of 20, a total of 15 completed subjects per sequence group (i.e., 15 subject who receive prasugrel first, then clopidogrel; and 15 subjects who receive clopidogrel first, then prasugrel) was determined.p-value: <0.000195% CI: [53.83, 69.31]Mixed Models Analysis
Secondary
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
Inhibition of platelet aggregation 1- and 24-hours after loading dose and 24-hours after last maintenance dose was administered was assessed using Accumetrics VerifyNow™ P2Y12 assay. Percentage inhibition, as reported by VerifyNow™ P2Y12, was calculated from PRU (rate and extent of 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.
Time frame: 1 hour and 24 hours after the loading dose (LD) and 24 hours after the last maintenance dose (LMD)
Population: Pharmacodynamic Population, which included all randomized participants who had blood draws for IPA, who met compliance criteria, and who had last dose of study drug prior to the blood draw for IPA.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Prasugrel | 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 After Loading Dose | 49.9 percent inhibition |
| Prasugrel | 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 | 24 Hours After Loading Dose | 87.1 percent inhibition |
| Prasugrel | 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 | 24 Hours After Last Maintenance Dose | 61.8 percent inhibition |
| Clopidogrel | 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 | 24 Hours After Loading Dose | 29.3 percent inhibition |
| Clopidogrel | 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 After Loading Dose | 13.4 percent inhibition |
| Clopidogrel | 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 | 24 Hours After Last Maintenance Dose | 44.2 percent inhibition |
Comparison: Null hypothesis: there was no difference between prasugrel and clopidogrel in IPA assessed by Accumetrics VerifyNow™ P2Y12 1 hour after administration of the loading dose.p-value: <0.000195% CI: [27.43, 45.52]Mixed Models Analysis
Comparison: Null hypothesis: there was no difference between prasugrel and clopidogrel in IPA assessed by Accumetrics VerifyNow™ P2Y12 24 hours after administration of the loading dose.p-value: <0.000195% CI: [49.56, 66.19]Mixed Models Analysis
Comparison: Null hypothesis: there was no difference between prasugrel and clopidogrel in IPA assessed by Accumetrics VerifyNow™ P2Y12 24 hours post-Last Maintenance Dose (LMD).p-value: <0.000195% CI: [10.27, 25.04]Mixed Models Analysis
Secondary
Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate
Thromboelastography (TEG) platelet mapping (MP) maximum amplitude (MA) - Adenosine Diphosphate (ADP) millimeters (mm) at each time point. The TEG-MP MA measures strength of clot formation in whole blood. MA-ADP is the maximal amplitude resulting from fibrin and platelets not blocked by ADP-receptor inhibiting drugs. Fibrin strands in blood sample link a rotating sample cup with a stationary pin suspended by a torsion wire. The degree of platelet contribution to the MA through platelet-fibrin bonding directly influences the magnitude of pin movement and ultimately the amplitude of the tracing.
Time frame: Baseline, 1 Hour, 4 Hours, and 24 Hours after loading dose, and 24 Hours after last maintenance dose
Population: Pharmacodynamic Population, which included all randomized participants who had blood draws for Inhibition of Platelet Function (IPF) as measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate (ADP), who met compliance criteria, and who had last dose of study drug prior to blood draw for IPF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Prasugrel | Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate | 1 Hour After Loading Dose | 38.5 millimeters (mm) |
| Prasugrel | Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate | 24 Hours After Loading Dose | 29.3 millimeters (mm) |
| Prasugrel | Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate | 4 Hours After Loading Dose | 24.2 millimeters (mm) |
| Prasugrel | Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate | 24 Hours After Last Maintenance Dose | 44.2 millimeters (mm) |
| Prasugrel | Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate | Baseline | 56.8 millimeters (mm) |
| Clopidogrel | Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate | 24 Hours After Last Maintenance Dose | 46.8 millimeters (mm) |
| Clopidogrel | Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate | Baseline | 58.1 millimeters (mm) |
| Clopidogrel | Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate | 1 Hour After Loading Dose | 54.8 millimeters (mm) |
| Clopidogrel | Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate | 4 Hours After Loading Dose | 48.1 millimeters (mm) |
| Clopidogrel | Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate | 24 Hours After Loading Dose | 49.2 millimeters (mm) |
Comparison: Null hypothesis: no difference between prasugrel and clopidogrel in Inhibition of Platelet Function as measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate (ADP).p-value: 0.523895% CI: [-5.35, 2.78]Mixed Models Analysis
Comparison: Null hypothesis: no difference between prasugrel and clopidogrel in Inhibition of Platelet Function as measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate (ADP).p-value: <0.000195% CI: [-21.15, -11.33]Mixed Models Analysis
Comparison: Null hypothesis: no difference between prasugrel and clopidogrel in Inhibition of Platelet Function as measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate (ADP).p-value: <0.000195% CI: [-29.67, -18.11]Mixed Models Analysis
Comparison: Null hypothesis: no difference between prasugrel and clopidogrel in Inhibition of Platelet Function as measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate (ADP).p-value: <0.000195% CI: [-24.97, -14.9]Mixed Models Analysis
Comparison: Null hypothesis: no difference between prasugrel and clopidogrel in Inhibition of Platelet Function as measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate (ADP).p-value: 0.372595% CI: [-8.46, 3.26]Mixed Models Analysis
Secondary
Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA)
Mean platelet aggregation (MPA) to 5 and 20 µM adenosine diphosphate (ADP) was assessed by light transmittance aggregometry (LTA). Platelet aggregation was monitored for a total of 7 minutes after addition of ADP. Maximum platelet aggregation was the maximal aggregation value achieved during the 7-minute observation period following addition of agonists.
Time frame: Baseline, 1 Hour, 4 Hours, and 24 Hours after loading dose, and 24 Hours after last maintenance dose
Population: Pharmacodynamic Population, which included all randomized participants who had blood draws for MPA, who met compliance criteria, and who had last dose of study drug prior to the blood draw for MPA.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Prasugrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | Baseline (5 μM ADP) | 64.9 percent platelet aggregation |
| Prasugrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | 1 Hour After Loading Dose (20 μM ADP) | 44.7 percent platelet aggregation |
| Prasugrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | 4 Hours After Loading Dose (20 μM ADP) | 22.4 percent platelet aggregation |
| Prasugrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | 1 Hour After Loading Dose (5 μM ADP) | 33.7 percent platelet aggregation |
| Prasugrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | 4 Hours After Loading Dose (5 μM ADP) | 18.0 percent platelet aggregation |
| Prasugrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | 24 Hours After Loading Dose (5 μM ADP) | 22.3 percent platelet aggregation |
| Prasugrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | 24 Hours After Last Maintenance Dose (5 μM ADP) | 29.6 percent platelet aggregation |
| Prasugrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | Baseline (20 μM ADP) | 77.1 percent platelet aggregation |
| Prasugrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | 24 Hours After Loading Dose (20 μM ADP) | 27.4 percent platelet aggregation |
| Prasugrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | 24 Hours After Last Maintenance Dose (20 μM ADP) | 38.3 percent platelet aggregation |
| Clopidogrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | 24 Hours After Last Maintenance Dose (20 μM ADP) | 50.7 percent platelet aggregation |
| Clopidogrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | 24 Hours After Last Maintenance Dose (5 μM ADP) | 38.3 percent platelet aggregation |
| Clopidogrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | 24 Hours After Loading Dose (20 μM ADP) | 58.4 percent platelet aggregation |
| Clopidogrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | Baseline (5 μM ADP) | 65.7 percent platelet aggregation |
| Clopidogrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | Baseline (20 μM ADP) | 76.9 percent platelet aggregation |
| Clopidogrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | 1 Hour After Loading Dose (5 μM ADP) | 56.7 percent platelet aggregation |
| Clopidogrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | 1 Hour After Loading Dose (20 μM ADP) | 69.8 percent platelet aggregation |
| Clopidogrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | 4 Hours After Loading Dose (5 μM ADP) | 44.6 percent platelet aggregation |
| Clopidogrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | 4 Hours After Loading Dose (20 μM ADP) | 57.5 percent platelet aggregation |
| Clopidogrel | Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA) | 24 Hours After Loading Dose (5 μM ADP) | 45.6 percent platelet aggregation |
Comparison: The null hypothesis was that there was no difference between prasugrel and clopidogrel in MPA assessed by Light Transmittance Aggregometry (LTA).p-value: 0.546695% CI: [-3.66, 1.97]Mixed Models Analysis
Comparison: The null hypothesis was that there was no difference between prasugrel and clopidogrel in MPA assessed by Light Transmittance Aggregometry (LTA).p-value: <0.000195% CI: [-28.45, -17.55]Mixed Models Analysis
Comparison: The null hypothesis was that there was no difference between prasugrel and clopidogrel in MPA assessed by Light Transmittance Aggregometry (LTA).p-value: <0.000195% CI: [-31.18, -22.02]Mixed Models Analysis
Comparison: The null hypothesis was that there was no difference between prasugrel and clopidogrel in MPA assessed by Light Transmittance Aggregometry (LTA).p-value: <0.000195% CI: [-27.42, -19.17]Mixed Models Analysis
Comparison: The null hypothesis was that there was no difference between prasugrel and clopidogrel in MPA assessed by Light Transmittance Aggregometry (LTA).p-value: 0.000195% CI: [-12.78, -4.58]Mixed Models Analysis
Comparison: The null hypothesis was that there was no difference between prasugrel and clopidogrel in MPA assessed by Light Transmittance Aggregometry (LTA).p-value: 0.877995% CI: [-2.8, 3.26]Mixed Models Analysis
Comparison: The null hypothesis was that there was no difference between prasugrel and clopidogrel in MPA assessed by Light Transmittance Aggregometry (LTA).p-value: <0.000195% CI: [-32.43, -17.87]Mixed Models Analysis
Comparison: The null hypothesis was that there was no difference between prasugrel and clopidogrel in MPA assessed by Light Transmittance Aggregometry (LTA).p-value: <0.000195% CI: [-40.32, -29.78]Mixed Models Analysis
Comparison: The null hypothesis was that there was no difference between prasugrel and clopidogrel in MPA assessed by Light Transmittance Aggregometry (LTA).p-value: <0.000195% CI: [-36.32, -25.66]Mixed Models Analysis
Comparison: The null hypothesis was that there was no difference between prasugrel and clopidogrel in MPA assessed by Light Transmittance Aggregometry (LTA).p-value: <0.000195% CI: [-17.19, -7.58]Mixed Models Analysis
Secondary
Platelet Reactivity Index (PRI)
Data from the Vasodilator-associated stimulated phosphoprotein assay were reported as the platelet reactivity index (PRI) which was calculated from corrected mean fluorescence intensity (cMFI) following incubation of platelets with either prostaglandin E1 (PGE1) alone or PGE1 plus ADP: Platelet Reactivity Index (%) = \[1-(cMFI PGEI+ADP/cMFI PGEI)\] x 100. Lower PRI values indicate greater platelet P2Y12 inhibition.
Time frame: Baseline, 1 Hour, 4 Hours, and 24 Hours after loading dose, and 24 Hours after last maintenance dose
Population: Pharmacodynamic Population, which included all randomized participants who had blood draws for Vasodilator-Associated Stimulated Phosphoprotein (VASP), who met compliance criteria, and who had last dose of study drug prior to the blood draw for inhibition of platelet function as assessed by VASP.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Prasugrel | Platelet Reactivity Index (PRI) | 24 Hours After Last Maintenance Dose | 27.4 percent inhibition |
| Prasugrel | Platelet Reactivity Index (PRI) | Baseline | 83.5 percent inhibition |
| Prasugrel | Platelet Reactivity Index (PRI) | 1 Hour After Loading Dose | 40.0 percent inhibition |
| Prasugrel | Platelet Reactivity Index (PRI) | 4 Hours After Loading Dose | 14.5 percent inhibition |
| Prasugrel | Platelet Reactivity Index (PRI) | 24 Hours After Loading Dose | 15.7 percent inhibition |
| Clopidogrel | Platelet Reactivity Index (PRI) | 24 Hours After Loading Dose | 58.5 percent inhibition |
| Clopidogrel | Platelet Reactivity Index (PRI) | 4 Hours After Loading Dose | 67.5 percent inhibition |
| Clopidogrel | Platelet Reactivity Index (PRI) | Baseline | 80.6 percent inhibition |
| Clopidogrel | Platelet Reactivity Index (PRI) | 24 Hours After Last Maintenance Dose | 42.3 percent inhibition |
| Clopidogrel | Platelet Reactivity Index (PRI) | 1 Hour After Loading Dose | 76.2 percent inhibition |
Comparison: The null hypothesis was that there was no difference between prasugrel and clopidogrel in Inhibition of Platelet Function as assessed by VASP.p-value: 0.369295% CI: [-3.6, 9.44]Mixed Models Analysis
Comparison: The null hypothesis was that there was no difference between prasugrel and clopidogrel in Inhibition of Platelet Function as assessed by VASP.p-value: <0.000195% CI: [-47.43, -24.98]Mixed Models Analysis
Comparison: The null hypothesis was that there was no difference between prasugrel and clopidogrel in Inhibition of Platelet Function as assessed by VASP.p-value: <0.000195% CI: [-61.89, -44.02]Mixed Models Analysis
Comparison: The null hypothesis was that there was no difference between prasugrel and clopidogrel in Inhibition of Platelet Function as assessed by VASP.p-value: <0.000195% CI: [-50.03, -35.55]Mixed Models Analysis
Comparison: The null hypothesis was that there was no difference between prasugrel and clopidogrel in Inhibition of Platelet Function as assessed by VASP.p-value: 0.001295% CI: [-23.42, -6.37]Mixed Models Analysis