Cangrelor Prasugrel 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 prasugrel and that patients treated with prasugrel 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 IV Cangrelor to Oral Prasugrel, and Prasugrel 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: Prasugrel


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 stable coronary artery disease defined by the following criteria 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). AND Treatment with aspirin (ASA) 81 mg daily.

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Day 1 - Cangrelor + Prasugrel (60mg) post infusion<br>Cangrelor IV + Oral prasugrel (60mg) administered within 5 minutes after cangrelor IV discontinuation | Drug: Cangrelor<br>* Cangrelor IV administered as a 30 µg/kg bolus, followed by 4 µg/kg/min infusion for two hours on study Days 1 and 8<br>Drug: Prasugrel<br>* Day 1: Subjects received prasugrel (60 mg) either during the initial cangrelor infusion (at 1.0 hours or 1.5 hours after infusion start) or within 5 minutes of discontinuing the cangrelor infusion. Subjects will be given either 5 or 6 additional 10-mg doses to be taken every 24 hours between Day 1 and Day 8.<br>|
| Experimental: Day 8 - Prasugrel (10mg) Dosing (5 doses)<br>Prasugrel discontinued 48h (n=6) prior to initiation of cangrelor infusion (2h) | Drug: Cangrelor<br>* Cangrelor IV administered as a 30 µg/kg bolus, followed by 4 µg/kg/min infusion for two hours on study Days 1 and 8<br>Drug: Prasugrel<br>* Day 1: Subjects received prasugrel (60 mg) either during the initial cangrelor infusion (at 1.0 hours or 1.5 hours after infusion start) or within 5 minutes of discontinuing the cangrelor infusion. Subjects will be given either 5 or 6 additional 10-mg doses to be taken every 24 hours between Day 1 and Day 8.<br>|
| Experimental: Day 1 - Cangrelor + Prasugrel (60mg) at 1.5h<br>Cangrelor IV + oral prasugrel (60mg) administered at 1.5h after the cangrelor infusion start time. | Drug: Cangrelor<br>* Cangrelor IV administered as a 30 µg/kg bolus, followed by 4 µg/kg/min infusion for two hours on study Days 1 and 8<br>Drug: Prasugrel<br>* Day 1: Subjects received prasugrel (60 mg) either during the initial cangrelor infusion (at 1.0 hours or 1.5 hours after infusion start) or within 5 minutes of discontinuing the cangrelor infusion. Subjects will be given either 5 or 6 additional 10-mg doses to be taken every 24 hours between Day 1 and Day 8.<br>|
| Experimental: Day 1 - Cangrelor + Prasugrel (60mg) a 1.0h<br>Cangrelor IV + oral prasugrel (60mg) administered at 1.0h after the cangrelor infusion start time. | Drug: Cangrelor<br>* Cangrelor IV administered as a 30 µg/kg bolus, followed by 4 µg/kg/min infusion for two hours on study Days 1 and 8<br>Drug: Prasugrel<br>* Day 1: Subjects received prasugrel (60 mg) either during the initial cangrelor infusion (at 1.0 hours or 1.5 hours after infusion start) or within 5 minutes of discontinuing the cangrelor infusion. Subjects will be given either 5 or 6 additional 10-mg doses to be taken every 24 hours between Day 1 and Day 8.<br>|
| Experimental: Day 8 - Prasugrel (10mg) Dosing (6 doses)<br>Prasugrel discontinued 24h prior to initiation of cangrelor infusion (2h) | Drug: Cangrelor<br>* Cangrelor IV administered as a 30 µg/kg bolus, followed by 4 µg/kg/min infusion for two hours on study Days 1 and 8<br>Drug: Prasugrel<br>* Day 1: Subjects received prasugrel (60 mg) either during the initial cangrelor infusion (at 1.0 hours or 1.5 hours after infusion start) or within 5 minutes of discontinuing the cangrelor infusion. Subjects will be given either 5 or 6 additional 10-mg doses to be taken every 24 hours between Day 1 and Day 8.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent of Preservation of Inhibitory Effect After Transition From Cangrelor to Prasugrel Compared With Effect Observed With Prasugrel Alone (Reference Timepoint) | A reference point for the effect of prasugrel alone was chosen for comparison and designated the final draw on study Day 1 (3.5 or 4.0 hours after cangrelor had been discontinued) as the reference for the effect of prasugrel. 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) and expressed as % aggregation in response to 20 micromolar (μM) adenosine diphosphate (ADP) at 300 seconds (final/terminal aggregation response). | Day 1 measures taken at timepoints after cangrelor infusion end to end of Day 1 measures. | 
| Extent of Preservation of Inhibitory Effect of Cangrelor Treatment After Prasugrel, Compared to Treatment With Cangrelor Alone | A reference point for the inhibitory effect of cangrelor alone was chosen for comparison and designated the first draw during the cangrelor infusion (1.0 or 1.5 hours) or within 5 minutes post cangrelor infusion on Day 1. The extent of aggregation was observed during the cangrelor infusion on Day 8, either 24 or 48 hours after discontinuation of prasugrel using light transmittance aggregometry (LTA) and expressed as % aggregation in response to 20 μM adenosine diphosphate (ADP) at 300 seconds (final/terminal aggregation response). | Day 8 - at 1.0 and 2.0 hours after initiation of cangrelor infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent of Preservation of Inhibitory Effect After Transition From Cangrelor to Prasugrel Compared With Effect Observed With Prasugrel Alone (Reference Timepoint) | A reference point for the effect of prasugrel alone was chosen for comparison and designated the final draw on study Day 1 (3.5 or 4.0 hours after cangrelor had been discontinued) as the reference for the effect of prasugrel. The extent of aggregation in the presence of absence of the study drugs was examined for each of the endpoints as assessed by platelet reaction units (PRU) from the VerifyNow P2Y12 assay. | Day 1 measures taken at timepoints after cangrelor infusion end to end of Day 1 measures. | 
| Extent of Preservation of Inhibitory Effect of Cangrelor Treatment After Prasugrel, Compared to Treatment With Cangrelor Alone | A reference point for the inhibitory effect of cangrelor alone was chosen for comparison and designated the first draw during the cangrelor infusion (1.0 or 1.5 hours) or within 5 minutes post cangrelor infusion on Day 1. The extent of aggregation was observed during the cangrelor infusion on Day 8, either 24 or 48 hours after discontinuation of prasugrel as assessed by platelet reaction units (PRU) from the VerifyNow P2Y12 assay. | Day 8 - at 1.0 and 2.0 hours after initiation of cangrelor infusion | 
| Bleeding Events in Accordance With the GUSTO Scale | Bleeding was assessed by history, physical exam, and complete blood count (CBC) that was performed on study Days 1 and 8. Reports of bleeding were to be evaluated by performance of a CBC. Bleeding was to be reported as recommended and quantified in accordance with the GUSTO criteria [The GUSTO Investigators, 1993]. | Day 1 through Day 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAD