Coronary Artery Disease
Conditions
Brief summary
To demonstrate that patients treated with cangrelor can be directly switched to oral ticagrelor and that patients treated with ticagrelor can be switched to cangrelor without a significant decrease in the extent of inhibition of platelet aggregation.
Interventions
DRUGcangrelor
Open-label cangrelor IV bolus (30 µg/kg), followed by an infusion of 4 µg/kg/min for two hours.
DRUGTicagrelor
Ticagrelor 180mg dose: administered 0.5 h or 1.5h after the initiation of cangrelor infusion Ticagrelor 90mg: 6 or 7 doses (depending on study arm) taken every 12 hours post cangrelor infusion.
Sponsors
The Medicines Company
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* greater than / equal to 18 and less than 75 years of age 1. Previous myocardial infarction defined by admission to the hospital with elevation of markers of injury or the presence of pathologic q waves on at least 2 contiguous electrocardiogram (ECG) leads. OR 2. Previous revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. AND 3. Treatment with aspirin (ASA) 81 mg daily.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Extent of Preservation of Inhibitory Effect Compared With Effect Observed With Cangrelor Alone (at Timepoint 1, Either at 0.5 Hours or 1.25 Hours) or Ticagrelor Alone (Measured 5.25 Hours After Initiation of Cangrelor on Day 1) | Day 1 measures taken at 2 timepoints after cangrelor infusion start: 0.5 or 1.5 hrs (Timepoint 1) and 5.25 hrs (TImepoint 2) | A reference point was chosen for comparison and designated the first draw during the cangrelor infusion (0.5 hours or 1.25 hours) as the reference for the effect of cangrelor and designated the final draw on study Day 1 (5.25 hours, or 3.25 hours after cangrelor had been discontinued) as the reference for the effect of ticagrelor. Residual platelet reactivity (the extent of aggregation in the presence or absence of the study drugs) was examined for each of the endpoints using light transmittance aggregometry. Residual platelet reactivity (PR) was measured in response to 20 µmol adenosine diphosphate (ADP) at 300 seconds (final/terminal aggregation response). |
| Extent of Preservation of Inhibitory Effect Compared With Effect Observed During Cangrelor Treatment After Ticagrelor | Day 5 at 1.0 and 2.0 hours after the initiation of cangrelor infusion | A reference point was chosen for comparison and designated the first draw during the cangrelor infusion (0.5 hours or 1.25 hours) as the reference for the effect of cangrelor. Residual platelet reactivity (the extent of aggregation in the presence or absence of the study drugs) was examined for each of the endpoints using light transmittance aggregometry (LTA). Residual platelet reactivity (PR) was measured in response to 20 µmol ADP at 300 seconds (final/terminal aggregation response). |
| Extent of Aggregation Response During Ticagrelor Treatment | Day 1 at 2.25, 2.5, 2.75, 3 and 4 hrs following initiation of cangrelor infusion | Blood samples were taken for platelet function studies to conduct pharmacodynamic assessments including LTA. A reference point was chosen for comparison and designated the first draw during the cangrelor infusion (0.5 hours or 1.25 hours) as the reference for the effect of cangrelor and designated the final draw on study Day 1 (5.25 hours, or 3.25 hours after cangrelor had been discontinued) as the reference for the effect of ticagrelor. Residual platelet reactivity (PR) (the extent of aggregation in the presence or absence of the study drugs) was examined for each of the endpoints using light transmittance aggregometry. Residual platelet reactivity was measured in response to 20 µmol ADP at 300 seconds (final/terminal aggregation response). |
Countries
United States
Participant flow
Recruitment details
The purpose of this study was to study the pharmacodynamic characteristics of transition from IV cangrelor to oral ticagrelor, and ticagrelor to cangrelor in patients with coronary artery disease. This was a single-center study, conducted in Jan-Feb 2013.
Pre-assignment details
Patients with coronary artery disease who were taking aspirin, but not P2Y12 inhibition were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| ITT Population - Ticagrelor 6 Doses On Day 1: Open-label cangrelor IV bolus (30 µg/kg), followed by an infusion of 4 µg/kg/min for two hours. Ticagrelor (180 mg) was administered at 0.5 h or 1.5 h after the initiation of cangrelor infusion. Patients were discharged and instructed to take 90 mg ticagrelor every 12 hours for 6 doses.
On Day 5: Cangrelor was administered after ticagrelor (90 mg)was discontinued 24 hours prior. | 6 |
| ITT Population - Ticagrelor 7 Doses On Day 1: Open-label cangrelor IV bolus (30 µg/kg), followed by an infusion of 4 µg/kg/min for two hours. Ticagrelor (180 mg) was administered at 0.5 h or 1.5 h after the initiation of cangrelor infusion. Patients were discharged and instructed to take 90 mg ticagrelor every 12 hours for 7 doses.
On Day 5: Cangrelor was administered after ticagrelor (90 mg)was discontinued 12 hours prior. | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | ITT Population - Ticagrelor 6 Doses | ITT Population - Ticagrelor 7 Doses | Total |
|---|---|---|---|
| Age, Continuous | 66.3 years STANDARD_DEVIATION 7.17 | 66.5 years STANDARD_DEVIATION 4.32 | 66.4 years STANDARD_DEVIATION 5.65 |
| Region of Enrollment United States | 6 participants | 6 participants | 12 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Extent of Aggregation Response During Ticagrelor Treatment
Blood samples were taken for platelet function studies to conduct pharmacodynamic assessments including LTA. A reference point was chosen for comparison and designated the first draw during the cangrelor infusion (0.5 hours or 1.25 hours) as the reference for the effect of cangrelor and designated the final draw on study Day 1 (5.25 hours, or 3.25 hours after cangrelor had been discontinued) as the reference for the effect of ticagrelor. Residual platelet reactivity (PR) (the extent of aggregation in the presence or absence of the study drugs) was examined for each of the endpoints using light transmittance aggregometry. Residual platelet reactivity was measured in response to 20 µmol ADP at 300 seconds (final/terminal aggregation response).
Time frame: Day 1 at 2.25, 2.5, 2.75, 3 and 4 hrs following initiation of cangrelor infusion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Extent of Aggregation Response During Ticagrelor Treatment | Reference 5.25 hours - PR | 4 percentage of platelet reactivity (PR) | Standard Deviation 3.4 |
| All Patients | Extent of Aggregation Response During Ticagrelor Treatment | 2.25 hours - PR | 12 percentage of platelet reactivity (PR) | Standard Deviation 11 |
| All Patients | Extent of Aggregation Response During Ticagrelor Treatment | 2.5 hours - PR | 19 percentage of platelet reactivity (PR) | Standard Deviation 16 |
| All Patients | Extent of Aggregation Response During Ticagrelor Treatment | 2.75 hours - PR | 10 percentage of platelet reactivity (PR) | Standard Deviation 9.2 |
| All Patients | Extent of Aggregation Response During Ticagrelor Treatment | 3 hours - PR | 7.1 percentage of platelet reactivity (PR) | Standard Deviation 6.3 |
| All Patients | Extent of Aggregation Response During Ticagrelor Treatment | 4 hours - PR | 4.6 percentage of platelet reactivity (PR) | Standard Deviation 3.6 |
| Cangrelor + Ticagrelor 180mg at 1.25 h of Cangrelor Infusion | Extent of Aggregation Response During Ticagrelor Treatment | 4 hours - PR | 2.5 percentage of platelet reactivity (PR) | Standard Deviation 1.9 |
| Cangrelor + Ticagrelor 180mg at 1.25 h of Cangrelor Infusion | Extent of Aggregation Response During Ticagrelor Treatment | Reference 5.25 hours - PR | 2.2 percentage of platelet reactivity (PR) | Standard Deviation 2.7 |
| Cangrelor + Ticagrelor 180mg at 1.25 h of Cangrelor Infusion | Extent of Aggregation Response During Ticagrelor Treatment | 2.75 hours - PR | 7.8 percentage of platelet reactivity (PR) | Standard Deviation 7.2 |
| Cangrelor + Ticagrelor 180mg at 1.25 h of Cangrelor Infusion | Extent of Aggregation Response During Ticagrelor Treatment | 3 hours - PR | 4.5 percentage of platelet reactivity (PR) | Standard Deviation 3.4 |
| Cangrelor + Ticagrelor 180mg at 1.25 h of Cangrelor Infusion | Extent of Aggregation Response During Ticagrelor Treatment | 2.25 hours - PR | 11 percentage of platelet reactivity (PR) | Standard Deviation 12 |
| Cangrelor + Ticagrelor 180mg at 1.25 h of Cangrelor Infusion | Extent of Aggregation Response During Ticagrelor Treatment | 2.5 hours - PR | 21 percentage of platelet reactivity (PR) | Standard Deviation 17 |
| Cangrelor + Ticagrelor 180mg at 0.5 h of Cangrelor Infusion | Extent of Aggregation Response During Ticagrelor Treatment | 2.25 hours - PR | 13 percentage of platelet reactivity (PR) | Standard Deviation 9.3 |
| Cangrelor + Ticagrelor 180mg at 0.5 h of Cangrelor Infusion | Extent of Aggregation Response During Ticagrelor Treatment | 2.5 hours - PR | 16 percentage of platelet reactivity (PR) | Standard Deviation 15 |
| Cangrelor + Ticagrelor 180mg at 0.5 h of Cangrelor Infusion | Extent of Aggregation Response During Ticagrelor Treatment | 4 hours - PR | 6.7 percentage of platelet reactivity (PR) | Standard Deviation 3.7 |
| Cangrelor + Ticagrelor 180mg at 0.5 h of Cangrelor Infusion | Extent of Aggregation Response During Ticagrelor Treatment | 2.75 hours - PR | 12 percentage of platelet reactivity (PR) | Standard Deviation 11 |
| Cangrelor + Ticagrelor 180mg at 0.5 h of Cangrelor Infusion | Extent of Aggregation Response During Ticagrelor Treatment | Reference 5.25 hours - PR | 5.8 percentage of platelet reactivity (PR) | Standard Deviation 3.1 |
| Cangrelor + Ticagrelor 180mg at 0.5 h of Cangrelor Infusion | Extent of Aggregation Response During Ticagrelor Treatment | 3 hours - PR | 10 percentage of platelet reactivity (PR) | Standard Deviation 7.6 |
Primary
Extent of Preservation of Inhibitory Effect Compared With Effect Observed During Cangrelor Treatment After Ticagrelor
A reference point was chosen for comparison and designated the first draw during the cangrelor infusion (0.5 hours or 1.25 hours) as the reference for the effect of cangrelor. Residual platelet reactivity (the extent of aggregation in the presence or absence of the study drugs) was examined for each of the endpoints using light transmittance aggregometry (LTA). Residual platelet reactivity (PR) was measured in response to 20 µmol ADP at 300 seconds (final/terminal aggregation response).
Time frame: Day 5 at 1.0 and 2.0 hours after the initiation of cangrelor infusion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Extent of Preservation of Inhibitory Effect Compared With Effect Observed During Cangrelor Treatment After Ticagrelor | 1.0 hours - PR | 1.5 percentage of platelet reactivity (PR) | Standard Deviation 1.5 |
| All Patients | Extent of Preservation of Inhibitory Effect Compared With Effect Observed During Cangrelor Treatment After Ticagrelor | 2.0 hours - PR | 1.3 percentage of platelet reactivity (PR) | Standard Deviation 1.6 |
| Cangrelor + Ticagrelor 180mg at 1.25 h of Cangrelor Infusion | Extent of Preservation of Inhibitory Effect Compared With Effect Observed During Cangrelor Treatment After Ticagrelor | 1.0 hours - PR | 1.5 percentage of platelet reactivity (PR) | Standard Deviation 1.6 |
| Cangrelor + Ticagrelor 180mg at 1.25 h of Cangrelor Infusion | Extent of Preservation of Inhibitory Effect Compared With Effect Observed During Cangrelor Treatment After Ticagrelor | 2.0 hours - PR | 1.2 percentage of platelet reactivity (PR) | Standard Deviation 1.5 |
| Cangrelor + Ticagrelor 180mg at 0.5 h of Cangrelor Infusion | Extent of Preservation of Inhibitory Effect Compared With Effect Observed During Cangrelor Treatment After Ticagrelor | 1.0 hours - PR | 1.5 percentage of platelet reactivity (PR) | Standard Deviation 1.5 |
| Cangrelor + Ticagrelor 180mg at 0.5 h of Cangrelor Infusion | Extent of Preservation of Inhibitory Effect Compared With Effect Observed During Cangrelor Treatment After Ticagrelor | 2.0 hours - PR | 1.5 percentage of platelet reactivity (PR) | Standard Deviation 1.9 |
Primary
Extent of Preservation of Inhibitory Effect Compared With Effect Observed With Cangrelor Alone (at Timepoint 1, Either at 0.5 Hours or 1.25 Hours) or Ticagrelor Alone (Measured 5.25 Hours After Initiation of Cangrelor on Day 1)
A reference point was chosen for comparison and designated the first draw during the cangrelor infusion (0.5 hours or 1.25 hours) as the reference for the effect of cangrelor and designated the final draw on study Day 1 (5.25 hours, or 3.25 hours after cangrelor had been discontinued) as the reference for the effect of ticagrelor. Residual platelet reactivity (the extent of aggregation in the presence or absence of the study drugs) was examined for each of the endpoints using light transmittance aggregometry. Residual platelet reactivity (PR) was measured in response to 20 µmol adenosine diphosphate (ADP) at 300 seconds (final/terminal aggregation response).
Time frame: Day 1 measures taken at 2 timepoints after cangrelor infusion start: 0.5 or 1.5 hrs (Timepoint 1) and 5.25 hrs (TImepoint 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Extent of Preservation of Inhibitory Effect Compared With Effect Observed With Cangrelor Alone (at Timepoint 1, Either at 0.5 Hours or 1.25 Hours) or Ticagrelor Alone (Measured 5.25 Hours After Initiation of Cangrelor on Day 1) | 1.75 hours - PR | 2.2 percentage of platelet reactivity (PR) | Standard Deviation 1.4 |
| All Patients | Extent of Preservation of Inhibitory Effect Compared With Effect Observed With Cangrelor Alone (at Timepoint 1, Either at 0.5 Hours or 1.25 Hours) or Ticagrelor Alone (Measured 5.25 Hours After Initiation of Cangrelor on Day 1) | Reference 0.5/1.25 hours - PR | 1.7 percentage of platelet reactivity (PR) | Standard Deviation 1.7 |
| All Patients | Extent of Preservation of Inhibitory Effect Compared With Effect Observed With Cangrelor Alone (at Timepoint 1, Either at 0.5 Hours or 1.25 Hours) or Ticagrelor Alone (Measured 5.25 Hours After Initiation of Cangrelor on Day 1) | 2.0 hours - PR | 2.3 percentage of platelet reactivity (PR) | Standard Deviation 2.2 |
| Cangrelor + Ticagrelor 180mg at 1.25 h of Cangrelor Infusion | Extent of Preservation of Inhibitory Effect Compared With Effect Observed With Cangrelor Alone (at Timepoint 1, Either at 0.5 Hours or 1.25 Hours) or Ticagrelor Alone (Measured 5.25 Hours After Initiation of Cangrelor on Day 1) | 1.75 hours - PR | 2 percentage of platelet reactivity (PR) | Standard Deviation 1.8 |
| Cangrelor + Ticagrelor 180mg at 1.25 h of Cangrelor Infusion | Extent of Preservation of Inhibitory Effect Compared With Effect Observed With Cangrelor Alone (at Timepoint 1, Either at 0.5 Hours or 1.25 Hours) or Ticagrelor Alone (Measured 5.25 Hours After Initiation of Cangrelor on Day 1) | Reference 0.5/1.25 hours - PR | 1.3 percentage of platelet reactivity (PR) | Standard Deviation 2 |
| Cangrelor + Ticagrelor 180mg at 1.25 h of Cangrelor Infusion | Extent of Preservation of Inhibitory Effect Compared With Effect Observed With Cangrelor Alone (at Timepoint 1, Either at 0.5 Hours or 1.25 Hours) or Ticagrelor Alone (Measured 5.25 Hours After Initiation of Cangrelor on Day 1) | 2.0 hours - PR | 1.2 percentage of platelet reactivity (PR) | Standard Deviation 1.9 |
| Cangrelor + Ticagrelor 180mg at 0.5 h of Cangrelor Infusion | Extent of Preservation of Inhibitory Effect Compared With Effect Observed With Cangrelor Alone (at Timepoint 1, Either at 0.5 Hours or 1.25 Hours) or Ticagrelor Alone (Measured 5.25 Hours After Initiation of Cangrelor on Day 1) | Reference 0.5/1.25 hours - PR | 2 percentage of platelet reactivity (PR) | Standard Deviation 1.5 |
| Cangrelor + Ticagrelor 180mg at 0.5 h of Cangrelor Infusion | Extent of Preservation of Inhibitory Effect Compared With Effect Observed With Cangrelor Alone (at Timepoint 1, Either at 0.5 Hours or 1.25 Hours) or Ticagrelor Alone (Measured 5.25 Hours After Initiation of Cangrelor on Day 1) | 2.0 hours - PR | 3.5 percentage of platelet reactivity (PR) | Standard Deviation 1.9 |
| Cangrelor + Ticagrelor 180mg at 0.5 h of Cangrelor Infusion | Extent of Preservation of Inhibitory Effect Compared With Effect Observed With Cangrelor Alone (at Timepoint 1, Either at 0.5 Hours or 1.25 Hours) or Ticagrelor Alone (Measured 5.25 Hours After Initiation of Cangrelor on Day 1) | 1.75 hours - PR | 2.3 percentage of platelet reactivity (PR) | Standard Deviation 1 |