Clinical trial NCT01979445: Cangrelor to Clopidogrel or Prasugrel Transition Study
Official title: A Study of the Transition From Cangrelor to Clopidogrel or Prasugrel in Patients With Coronary Artery Disease.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronary Artery Disease (CAD)
Keywords: CAD
Lead sponsor: The Medicines Company
Sponsor class: INDUSTRY
First posted: 2013-11-08
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: There are two separate objectives in this study:

1. To demonstrate the pharmacodynamic (PD) profile when participants treated with cangrelor are switched to oral prasugrel 60 mg administered 30 minutes (min) after cangrelor infusion is discontinued
2. To demonstrate the PD profile when participants treated with cangrelor are switched to oral clopidogrel 600 mg administered during or immediately after cangrelor infusion.


Eligibility criteria: Inclusion Criteria:

1. Greater than or equal to 18 and less than 75 years of age, of either sex, and of any race.
2. Stable CAD 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 or coronary artery bypass graft, and
   3. Treatment with aspirin 81 mg daily.

Exclusion Criteria:

1. Known intolerance or contraindication to cangrelor or prasugrel, or any ingredients of the respective formulation.
2. Any antiplatelet (other than aspirin) or anticoagulant medication within the previous 30 days.
3. Acute coronary syndrome within the previous 12 months.
4. History of bleeding diathesis or known coagulopathy such as; impaired hemostasis; known international normalized ratio (INR) \>1.5; past or present bleeding disorder (including congenital bleeding disorders, such as, von Willebrand's disease or hemophilia), acquired bleeding disorders, and unexplained clinically significant bleeding disorders; thrombocytopenia (platelet count less than 100,000/microliter \[µL\]), or history of thrombocytopenia or neutropenia associated with clopidogrel.
5. Anemia (for example, hematocrit less than 35%).
6. Prior stroke (any type), prior cerebral arteriovenous malformation or intracranial aneurysm; recent (\<1 month) trauma or major surgery (including bypass surgery).
7. Known or suspected pregnancy, or lactating females.
8. Known severe renal insufficiency (glomerular filtration rate less than 30 milliliter \[mL\]/min).
9. Inability to provide informed consent.
10. Moderate or severe hepatic impairment as per Investigator's discretion (elevation of liver function tests).
11. Inability to swallow oral medication at time of randomization.
12. Any clinically significant disease or condition affecting a major organ system, including but not limited to gastrointestinal, renal, hepatic, endocrinologic, broncho-pulmonary, neurological, or metabolic disease.
13. Any surgical or medical condition which, in the judgment of the Investigator, might interfere with the pharmacokinetics, distribution, metabolism, or excretion of the study drug (if applicable).
14. Treatment with other investigational medicinal products or devices within 30 days or 5 half-lives, whichever is longer, prior to the administration of the drug, or planned use of investigational medicinal products or devices.
15. Participants who, for any reason, are deemed by the Investigator to be inappropriate for this study, including participants who are unable to communicate or to cooperate with the Investigator.
16. Participant is the Investigator or his/her deputy, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study.
17. Active pathological bleeding, or a history of transient ischemic attack.

Primary outcomes:
measure: Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone
timeFrame: Day 1 at 5.5 or 6 hrs after administration of prasugrel or clopidogrel (reference) and Day 1 at 2.25, 2.5, 2.75, 3, 4, and 5.5 hrs after initiation of cangrelor infusion
measure: Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone
timeFrame: Day 1 at 1, 1.5, 2, or 2.5 hrs after administration of prasugrel or clopidogrel (reference) and Day 1 at 1.75 and 2 hrs after initiation of cangrelor infusion
Secondary outcomes:
measure: Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor to Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone Determined By VerifyNow P2Y12 Assay
timeFrame: Day 1 at 5.5 or 6 hrs after administration of prasugrel or clopidogrel (reference) and Day 1 at 2.25, 2.5, 2.75, 3, 4, and 5.5 hrs after initiation of cangrelor infusion
measure: Extent of Preservation of Platelet Inhibitory Effect of Cangrelor Treatment After Prasugrel or Clopidogrel Compared to Treatment With Cangrelor Alone Determined By VerifyNow P2Y12 Assay
timeFrame: Day 1 at 1, 1.5, 2, or 2.5 hrs after administration of prasugrel or clopidogrel (reference) and Day 1 at 1.75 and 2 hrs after initiation of cangrelor infusion
measure: Bleeding Events In Accordance With GUSTO Scale
timeFrame: Screening through the follow-up period (5 to 7 days after Day 1)
Other outcomes:
Locations:
city: Burlington
country: United States
facility: Fletcher Allen Health Care
state: Vermont
Study officials:
affiliation: University of Vermont Medical Center
name: David J. Schneider, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schneider DJ, Agarwal Z, Seecheran N, Gogo P. Pharmacodynamic Effects When Clopidogrel is Given Before Cangrelor Discontinuation. J Interv Cardiol. 2015 Oct;28(5):415-9. doi: 10.1111/joic.12229. Epub 2015 Sep 18.