Cangrelor to Clopidogrel or Prasugrel Transition Study | NCT01979445

NCT01979445

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Prasugrel 30 Min After Cangrelor	Experimental	Prasugrel 60 milligram (mg) administered orally 30 min after the discontinuation of cangrelor infusion on Day 1 (2.5 hours [hrs] after initiation of cangrelor infusion).	Drug: Cangrelor Drug: Prasugrel
Clopidogrel Within 5 Min After Cangrelor	Experimental	Clopidogrel 600 mg administered orally within 5 min after the discontinuation of the cangrelor infusion on Day 1 (2 hrs after initiation of cangrelor infusion).	Drug: Cangrelor Drug: Clopidogrel
Clopidogrel 1.5 Hrs During Cangrelor	Experimental	Clopidogrel 600 mg administered orally 1.5 hrs after the initiation of cangrelor infusion on Day 1.	Drug: Cangrelor Drug: Clopidogrel
Clopidogrel 1 Hr During Cangrelor	Experimental	Clopidogrel 600 mg administered orally 1 hr after the initiation of cangrelor infusion on Day 1.	Drug: Cangrelor Drug: Clopidogrel

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Cangrelor	Drug	Cangrelor intravenously (IV) administered as a 30 microgram (µg)/kilogram (kg) bolus, followed by 4 µg/kg/min infusion for 2 hrs on Day 1.	Clopidogrel 1 Hr During Cangrelor

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone	A reference point for prasugrel or clopidogrel was chosen for comparison and designated at 6 or 5.5 hrs after the administration of prasugrel or clopidogrel as the reference for the effect of the oral drug. Platelet function was assessed using light transmittance aggregometry (LTA). LTA measures the aggregation or cross linking of platelets by fibrinogen and requires the activation of platelets plus the binding of fibrinogen. The extent of aggregation was expressed as % aggregation in response to 20 micromolar (μM) adenosine diphosphate (ADP) at 300 seconds (sec) (final/terminal aggregation response).	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
Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone	A reference point for cangrelor was chosen for comparison and designated as the administration time of prasugrel 60 mg or clopidogrel 600 mg (2.5, 2, 1.5, or 1 hrs). Platelet function was assessed using LTA. LTA measures the aggregation or cross linking of platelets by fibrinogen and requires the activation of platelets plus the binding of fibrinogen. The extent of aggregation was examined using LTA and expressed as % aggregation in response to 20 μM ADP at 300 sec (final/terminal aggregation response).	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	Description	Time Frame
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	A reference point for prasugrel or clopidogrel was chosen for comparison and designated at 6 or 5.5 hrs after the administration of prasugrel or clopidogrel as the reference for the effect of the oral drug. Platelet function was assessed using the VerifyNow P2Y12 assay. The VerifyNow P2Y12 assay measures the aggregation or cross linking of platelets by fibrinogen and requires the activation of platelets plus the binding of fibrinogen. The extent of aggregation was assessed by platelet reaction units (PRU), determined by the VerifyNow P2Y12 assay. The VerifyNow P2Y12 assay is designed to directly measure the effects of drugs on the P2Y12 receptor, using prostaglandin E1 in addition to ADP to increase intraplatelet cyclic adenosine monophosphate (cAMP). Platelet reactivity was expressed in PRU.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Greater than or equal to 18 and less than 75 years of age, of either sex, and of any race.
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:

Known intolerance or contraindication to cangrelor or prasugrel, or any ingredients of the respective formulation.
Any antiplatelet (other than aspirin) or anticoagulant medication within the previous 30 days.
Acute coronary syndrome within the previous 12 months.
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.
Anemia (for example, hematocrit less than 35%).
Prior stroke (any type), prior cerebral arteriovenous malformation or intracranial aneurysm; recent (<1 month) trauma or major surgery (including bypass surgery).
Known or suspected pregnancy, or lactating females.
Known severe renal insufficiency (glomerular filtration rate less than 30 milliliter [mL]/min).
Inability to provide informed consent.
Moderate or severe hepatic impairment as per Investigator's discretion (elevation of liver function tests).
Inability to swallow oral medication at time of randomization.
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.
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).
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.
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.
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.
Active pathological bleeding, or a history of transient ischemic attack.

Name	Affiliation	Role
David J. Schneider, MD	University of Vermont Medical Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Fletcher Allen Health Care		Burlington	Vermont	05401	United States

PubMed Identifier	Type	Citation	Retractions
26381736	Result	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.

Arm/Group Information

ID	Title	Description
FG000	Prasugrel 30 Min After Cangrelor	Cangrelor intravenously (IV) was administered on Day 1 as a 30 microgram (μg)/kilogram (kg) bolus, followed by 4 μg/kg/minute (min) infusion for 2 hours (hrs). Prasugrel 60 milligram (mg) was administered on Day 1 as a single oral dose 30 min after the discontinuation of cangrelor infusion (2.5 hrs after initiation of cangrelor infusion).
FG001	Clopidogrel Within 5 Min After Cangrelor	Cangrelor IV was administered on Day 1 as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs. Clopidogrel 600 mg was administered on Day 1 as a single oral dose within 5 min after the discontinuation of the cangrelor infusion (2 hrs after initiation of cangrelor infusion).
FG002	Clopidogrel 1.5 Hrs During Cangrelor	Cangrelor IV was administered on Day 1 as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs. Clopidogrel 600 mg was administered on Day 1 as a single oral dose 1.5 hrs following the initiation of cangrelor infusion.
FG003	Clopidogrel 1 Hr During Cangrelor	Cangrelor IV was administered on Day 1 as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs. Clopidogrel 600 mg was administered on Day 1 as a single oral dose 1 hr following the initiation of cangrelor infusion.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Prasugrel	Cangrelor IV was administered on Day 1 as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs. Prasugrel 60 mg was administered on Day 1 as a single oral dose 30 min on Day 1 after the discontinuation of cangrelor infusion.
BG001	Clopidogrel

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone

A reference point for prasugrel or clopidogrel was chosen for comparison and designated at 6 or 5.5 hrs after the administration of prasugrel or clopidogrel as the reference for the effect of the oral drug. Platelet function was assessed using light transmittance aggregometry (LTA). LTA measures the aggregation or cross linking of platelets by fibrinogen and requires the activation of platelets plus the binding of fibrinogen. The extent of aggregation was expressed as % aggregation in response to 20 micromolar (μM) adenosine diphosphate (ADP) at 300 seconds (sec) (final/terminal aggregation response).

Participants treated with cangrelor and prasugrel or clopidogrel were used for the analysis and presentation of data.

Posted

Mean

Standard Deviation

% aggregation

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

ID	Title

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Prasugrel 30 Min After Cangrelor	Cangrelor IV was administered on Day 1 as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs. Prasugrel 60 mg was administered on Day 1 as a single oral dose 30 min after the discontinuation of cangrelor infusion (2.5 hrs after initiation of cangrelor infusion).

ID	Term
D003327	Coronary Disease
D017202	Myocardial Ischemia
D006331	Heart Diseases
D002318	Cardiovascular Diseases

ID	Term
C117446	cangrelor
D000077144	Clopidogrel
D000068799	Prasugrel Hydrochloride

ID	Term
D013988	Ticlopidine
D058924	Thienopyridines
D013876	Thiophenes
D013457	Sulfur Compounds

OG000	Prasugrel 30 Min After Cangrelor	Cangrelor IV was administered on Day 1 as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs. Prasugrel 60 mg was administered on Day 1 as a single oral dose 30 min after the discontinuation of cangrelor infusion (2.5 hrs after initiation of cangrelor infusion).
OG001	Clopidogrel Within 5 Min After Cangrelor	Cangrelor IV was administered on Day 1 as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs. Clopidogrel 600 mg was administered on Day 1 as a single oral dose within 5 min after the discontinuation of the cangrelor infusion (2 hrs after initiation of cangrelor infusion).
OG002	Clopidogrel 1.5 Hrs During Cangrelor	Cangrelor IV was administered on Day 1 as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs. Clopidogrel 600 mg was administered on Day 1 as a single oral dose 1.5 hrs following the initiation of cangrelor infusion.
OG003	Clopidogrel 1 Hr During Cangrelor	Cangrelor IV was administered on Day 1 as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs. Clopidogrel 600 mg was administered on Day 1 as a single oral dose 1 hr following the initiation of cangrelor infusion.