Cangrelor Prasugrel Transition Study

A Study of the Transition From IV Cangrelor to Oral Prasugrel, and Prasugrel to Cangrelor, in Patients With Coronary Artery Disease.

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Cangrelor; Drug: Prasugrel

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. greater than / equal to 18 and less than 75 years of age

2. stable coronary artery disease defined by the following criteria

   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).

      AND

   3. Treatment with aspirin (ASA) 81 mg daily.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Day 1 - Cangrelor + Prasugrel (60mg) post infusion; Cangrelor IV + Oral prasugrel (60mg) administered within 5 minutes after cangrelor IV discontinuation	Drug: Cangrelor; 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; Drug: Prasugrel; 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.
Experimental: Day 8 - Prasugrel (10mg) Dosing (5 doses); Prasugrel discontinued 48h (n=6) prior to initiation of cangrelor infusion (2h)	Drug: Cangrelor; 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; Drug: Prasugrel; 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.
Experimental: Day 1 - Cangrelor + Prasugrel (60mg) at 1.5h; Cangrelor IV + oral prasugrel (60mg) administered at 1.5h after the cangrelor infusion start time.	Drug: Cangrelor; 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; Drug: Prasugrel; 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.
Experimental: Day 1 - Cangrelor + Prasugrel (60mg) a 1.0h; Cangrelor IV + oral prasugrel (60mg) administered at 1.0h after the cangrelor infusion start time.	Drug: Cangrelor; 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; Drug: Prasugrel; 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.
Experimental: Day 8 - Prasugrel (10mg) Dosing (6 doses); Prasugrel discontinued 24h prior to initiation of cangrelor infusion (2h)	Drug: Cangrelor; 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; Drug: Prasugrel; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The Medicines Company
• Investigators: Principal Investigator: David J. Schneider, University of Vermont Medical Center

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: May 6, 2013
• First Submitted That Met QC Criteria: May 8, 2013
• First Posted (Estimate): May 13, 2013

Study Record Updates

• Last Update Posted (Estimate): June 24, 2015
• Last Update Submitted That Met QC Criteria: May 27, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: CAD
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Prasugrel Hydrochloride; Cangrelor
• Other Study ID Numbers: MDCO-CAN-13-01