Trial Outcomes & Findings for Third Optimizing Anti-Platelet Therapy in Diabetes MellitUS (OPTIMUS-3) (NCT NCT00642174)
NCT ID: NCT00642174
Last Updated: 2010-02-23
Results Overview
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.
COMPLETED
PHASE2
35 participants
4 hours after loading dose
2010-02-23
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Period 1 - Initial Drug
STARTED
|
18
|
17
|
|
Period 1 - Initial Drug
COMPLETED
|
18
|
16
|
|
Period 1 - Initial Drug
NOT COMPLETED
|
0
|
1
|
|
Period 2 - Crossover Drug
STARTED
|
18
|
16
|
|
Period 2 - Crossover Drug
COMPLETED
|
18
|
16
|
|
Period 2 - Crossover Drug
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Period 1 - Initial Drug
Entry Criteria Not Met
|
0
|
1
|
Baseline Characteristics
Third Optimizing Anti-Platelet Therapy in Diabetes MellitUS (OPTIMUS-3)
Baseline characteristics by cohort
| Measure |
Prasugrel Then Clopidogrel
n=18 Participants
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.
|
Clopidogrel Then Prasugrel
n=17 Participants
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.
|
Total
n=35 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
60.3 years
STANDARD_DEVIATION 9.43 • n=99 Participants
|
62.4 years
STANDARD_DEVIATION 8.14 • n=107 Participants
|
61.3 years
STANDARD_DEVIATION 8.76 • n=206 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
24 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
8 participants
n=99 Participants
|
7 participants
n=107 Participants
|
15 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
African
|
3 participants
n=99 Participants
|
4 participants
n=107 Participants
|
7 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
4 participants
n=99 Participants
|
4 participants
n=107 Participants
|
8 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Native American
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
1 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
East Asian
|
1 participants
n=99 Participants
|
0 participants
n=107 Participants
|
1 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
West Asian
|
2 participants
n=99 Participants
|
1 participants
n=107 Participants
|
3 participants
n=206 Participants
|
|
Region of Enrollment
United States
|
18 participants
n=99 Participants
|
17 participants
n=107 Participants
|
35 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 4 hours after loading dosePopulation: 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.
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.
Outcome measures
| Measure |
Prasugrel
n=34 Participants
Prasugrel: Oral prasugrel 60-mg loading dose, followed by 6 to 9 days of prasugrel 10-mg/day tablet maintenance dose.
|
Clopidogrel
n=35 Participants
Clopidogrel: Oral clopidogrel 600-mg loading dose, followed by 6 to 9 days of clopidogrel 150-mg/day tablet maintenance dose.
|
|---|---|---|
|
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 • Interval 5.55 to 13.18
|
9.3 percent inhibition
95% Confidence Interval 11.46 • Interval 5.55 to 13.15
|
|
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 9.40 • Interval 82.96 to 95.6
|
27.7 percent inhibition
95% Confidence Interval 23.82 • Interval 21.49 to 33.94
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Prasugrel
n=34 Participants
Prasugrel: Oral prasugrel 60-mg loading dose, followed by 6 to 9 days of prasugrel 10-mg/day tablet maintenance dose.
|
Clopidogrel
n=35 Participants
Clopidogrel: Oral clopidogrel 600-mg loading dose, followed by 6 to 9 days of clopidogrel 150-mg/day tablet maintenance dose.
|
|---|---|---|
|
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
Interval 41.17 to 58.6
|
13.4 percent inhibition
Interval 4.92 to 21.89
|
|
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
Interval 80.64 to 93.66
|
29.3 percent inhibition
Interval 22.87 to 35.68
|
|
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
Interval 55.7 to 67.91
|
44.2 percent inhibition
Interval 38.05 to 50.26
|
SECONDARY outcome
Timeframe: Baseline, 1 Hour, 4 Hours, and 24 Hours after loading dose, and 24 Hours after last maintenance dosePopulation: 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.
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.
Outcome measures
| Measure |
Prasugrel
n=34 Participants
Prasugrel: Oral prasugrel 60-mg loading dose, followed by 6 to 9 days of prasugrel 10-mg/day tablet maintenance dose.
|
Clopidogrel
n=35 Participants
Clopidogrel: Oral clopidogrel 600-mg loading dose, followed by 6 to 9 days of clopidogrel 150-mg/day tablet maintenance dose.
|
|---|---|---|
|
Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA)
Baseline (5 μM ADP)
|
64.9 percent platelet aggregation
Interval 61.62 to 68.14
|
65.7 percent platelet aggregation
Interval 62.49 to 68.95
|
|
Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA)
1 Hour After Loading Dose (5 μM ADP)
|
33.7 percent platelet aggregation
Interval 28.44 to 39.03
|
56.7 percent platelet aggregation
Interval 51.69 to 61.77
|
|
Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA)
4 Hours After Loading Dose (5 μM ADP)
|
18.0 percent platelet aggregation
Interval 13.41 to 22.51
|
44.6 percent platelet aggregation
Interval 40.11 to 49.0
|
|
Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA)
24 Hours After Loading Dose (5 μM ADP)
|
22.3 percent platelet aggregation
Interval 17.78 to 26.89
|
45.6 percent platelet aggregation
Interval 41.2 to 50.06
|
|
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
Interval 25.2 to 34.08
|
38.3 percent platelet aggregation
Interval 33.93 to 42.71
|
|
Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA)
Baseline (20 μM ADP)
|
77.1 percent platelet aggregation
Interval 73.74 to 80.43
|
76.9 percent platelet aggregation
Interval 73.54 to 80.17
|
|
Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA)
1 Hour After Loading Dose (20 μM ADP)
|
44.7 percent platelet aggregation
Interval 38.54 to 50.77
|
69.8 percent platelet aggregation
Interval 64.05 to 75.56
|
|
Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA)
4 Hours After Loading Dose (20 μM ADP)
|
22.4 percent platelet aggregation
Interval 16.99 to 27.81
|
57.5 percent platelet aggregation
Interval 52.16 to 62.75
|
|
Maximum Platelet Aggregation (MPA) as Assessed by Light Transmittance Aggregometry (LTA)
24 Hours After Loading Dose (20 μM ADP)
|
27.4 percent platelet aggregation
Interval 22.23 to 32.67
|
58.4 percent platelet aggregation
Interval 53.39 to 63.48
|
|
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
Interval 32.97 to 43.64
|
50.7 percent platelet aggregation
Interval 45.42 to 55.97
|
SECONDARY outcome
Timeframe: Baseline, 1 Hour, 4 Hours, and 24 Hours after loading dose, and 24 Hours after last maintenance dosePopulation: 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.
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.
Outcome measures
| Measure |
Prasugrel
n=34 Participants
Prasugrel: Oral prasugrel 60-mg loading dose, followed by 6 to 9 days of prasugrel 10-mg/day tablet maintenance dose.
|
Clopidogrel
n=35 Participants
Clopidogrel: Oral clopidogrel 600-mg loading dose, followed by 6 to 9 days of clopidogrel 150-mg/day tablet maintenance dose.
|
|---|---|---|
|
Platelet Reactivity Index (PRI)
24 Hours After Loading Dose
|
15.7 percent inhibition
Interval 8.33 to 22.99
|
58.5 percent inhibition
Interval 51.3 to 65.61
|
|
Platelet Reactivity Index (PRI)
Baseline
|
83.5 percent inhibition
Interval 78.76 to 88.31
|
80.6 percent inhibition
Interval 75.92 to 85.31
|
|
Platelet Reactivity Index (PRI)
1 Hour After Loading Dose
|
40.0 percent inhibition
Interval 32.14 to 47.8
|
76.2 percent inhibition
Interval 68.48 to 83.88
|
|
Platelet Reactivity Index (PRI)
4 Hours After Loading Dose
|
14.5 percent inhibition
Interval 7.73 to 21.35
|
67.5 percent inhibition
Interval 60.79 to 74.19
|
|
Platelet Reactivity Index (PRI)
24 Hours After Last Maintenance Dose
|
27.4 percent inhibition
Interval 20.82 to 34.03
|
42.3 percent inhibition
Interval 35.72 to 48.93
|
SECONDARY outcome
Timeframe: Baseline, 1 Hour, 4 Hours, and 24 Hours after loading dose, and 24 Hours after last maintenance dosePopulation: 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.
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.
Outcome measures
| Measure |
Prasugrel
n=34 Participants
Prasugrel: Oral prasugrel 60-mg loading dose, followed by 6 to 9 days of prasugrel 10-mg/day tablet maintenance dose.
|
Clopidogrel
n=35 Participants
Clopidogrel: Oral clopidogrel 600-mg loading dose, followed by 6 to 9 days of clopidogrel 150-mg/day tablet maintenance dose.
|
|---|---|---|
|
Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate
Baseline
|
56.8 millimeters (mm)
Interval 52.37 to 61.21
|
58.1 millimeters (mm)
Interval 53.7 to 62.45
|
|
Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate
1 Hour After Loading Dose
|
38.5 millimeters (mm)
Interval 33.42 to 43.63
|
54.8 millimeters (mm)
Interval 49.84 to 59.69
|
|
Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate
4 Hours After Loading Dose
|
24.2 millimeters (mm)
Interval 18.8 to 29.6
|
48.1 millimeters (mm)
Interval 42.84 to 53.35
|
|
Inhibition of Platelet Function as Measured by Thromboelastography (TEG)-Platelet Mapping Maximum Amplitude - Adenosine Diphosphate
24 Hours After Loading Dose
|
29.3 millimeters (mm)
Interval 24.56 to 34.01
|
49.2 millimeters (mm)
Interval 44.61 to 53.82
|
|
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)
Interval 38.77 to 49.62
|
46.8 millimeters (mm)
Interval 41.37 to 52.22
|
Adverse Events
Prasugrel
Clopidogrel
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Prasugrel
n=34 participants at risk
Prasugrel: Oral prasugrel 60-mg loading dose, followed by 6 to 9 days of prasugrel 10-mg/day tablet maintenance dose.
|
Clopidogrel
n=35 participants at risk
Clopidogrel: Oral clopidogrel 600-mg loading dose, followed by 6 to 9 days of clopidogrel 150-mg/day tablet maintenance dose.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/34
|
2.9%
1/35 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/34
|
2.9%
1/35 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/34
|
2.9%
1/35 • Number of events 1
|
|
General disorders
Vessel puncture site haemorrhage
|
2.9%
1/34 • Number of events 1
|
0.00%
0/35
|
|
Infections and infestations
Sinusitis
|
0.00%
0/34
|
2.9%
1/35 • Number of events 3
|
|
Infections and infestations
Upper respiratory tract infection
|
2.9%
1/34 • Number of events 1
|
2.9%
1/35 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
2.9%
1/34 • Number of events 1
|
0.00%
0/35
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/34
|
2.9%
1/35 • Number of events 2
|
|
Investigations
Haematocrit decreased
|
2.9%
1/34 • Number of events 1
|
0.00%
0/35
|
|
Investigations
Haemoglobin decreased
|
2.9%
1/34 • Number of events 1
|
0.00%
0/35
|
|
Metabolism and nutrition disorders
Electrolyte imbalance
|
0.00%
0/34
|
2.9%
1/35 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.9%
1/34 • Number of events 2
|
0.00%
0/35
|
|
Nervous system disorders
Headache
|
2.9%
1/34 • Number of events 1
|
5.7%
2/35 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/34
|
2.9%
1/35 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
0.00%
0/34
|
2.9%
1/35 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/34
|
2.9%
1/35 • Number of events 1
|
|
Surgical and medical procedures
Wart excision
|
0.00%
0/34
|
2.9%
1/35 • Number of events 1
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/34
|
2.9%
1/35 • Number of events 1
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60