Cangrelor Ticagrelor Transition Study

Study Overview
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Brief Summary
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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.

Official Title
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A Study of the Transition From Cangrelor to Ticagrelor, and Ticagrelor to Cangrelor in Patients With Coronary Artery Disease

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: cangrelor
* Drug: Ticagrelor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: greater than / equal to 18 and less than 75 years of age 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 Previous revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. AND Treatment with aspirin (ASA) 81 mg daily. Exclusion Criteria:

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cangrelor IV + Ticagrelor 180mg at 0.5 hr<br>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 after the initiation of cangrelor infusion. | Drug: cangrelor<br>* Open-label cangrelor IV bolus (30 µg/kg), followed by an infusion of 4 µg/kg/min for two hours.<br>Drug: Ticagrelor<br>* 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.<br>* Other names: Brilinta;|
| Experimental: Cangrelor IV + Ticagrelor 90mg (7 doses)<br>On Day 1: Following completion of cangrelor and ticagrelor dosing, patients were discharged and instructed to take 90 mg ticagrelor every 12 hours for 7 doses (12, 24, 36, 48, 60, 72, and 84 h). On Day 5: 12 h post last ticagrelor dose (90 mg), patients received another open-label cangrelor IV bolus (30 µg/kg), followed by an infusion of 4 µg/kg/min for two hours. | Drug: cangrelor<br>* Open-label cangrelor IV bolus (30 µg/kg), followed by an infusion of 4 µg/kg/min for two hours.<br>Drug: Ticagrelor<br>* 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.<br>* Other names: Brilinta;|
| Experimental: Cangrelor IV + Ticagrelor 180mg at 1.5 hr<br>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 1.5 h after the initiation of cangrelor infusion. | Drug: cangrelor<br>* Open-label cangrelor IV bolus (30 µg/kg), followed by an infusion of 4 µg/kg/min for two hours.<br>Drug: Ticagrelor<br>* 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.<br>* Other names: Brilinta;|
| Experimental: Cangrelor IV + Ticagrelor 90mg (6 doses)<br>On Day 1: Following completion of cangrelor and ticagrelor dosing, patients were discharged and instructed to take 90 mg ticagrelor every 12 hours for 6 doses (12, 24, 36, 48, 60, and 72 h). On Day 5: 24 h post last ticagrelor dose (90 mg), patients received another open-label cangrelor IV bolus (30 µg/kg), followed by an infusion of 4 µg/kg/min for two hours. | Drug: cangrelor<br>* Open-label cangrelor IV bolus (30 µg/kg), followed by an infusion of 4 µg/kg/min for two hours.<br>Drug: Ticagrelor<br>* 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.<br>* Other names: Brilinta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 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) | 
| 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). | Day 5 at 1.0 and 2.0 hours after the initiation of cangrelor infusion | 
| 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). | Day 1 at 2.25, 2.5, 2.75, 3 and 4 hrs following initiation of cangrelor infusion |