BRIDGE: Cangrelor to Clopidogrel or Prasugrel Transition Study
Study Details
Study Description
Brief Summary
There are two separate objectives in this study:
-
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
-
To demonstrate the PD profile when participants treated with cangrelor are switched to oral clopidogrel 600 mg administered during or immediately after cangrelor infusion.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Prasugrel 30 Min After Cangrelor 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
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.
Drug: Prasugrel
Prasugrel 60 mg single oral dose
|
| Experimental: Clopidogrel Within 5 Min After Cangrelor 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
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.
Drug: Clopidogrel
Clopidogrel 600 mg single oral dose
|
| Experimental: Clopidogrel 1.5 Hrs During Cangrelor Clopidogrel 600 mg administered orally 1.5 hrs after the initiation of cangrelor infusion on Day 1. |
Drug: Cangrelor
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.
Drug: Clopidogrel
Clopidogrel 600 mg single oral dose
|
| Experimental: Clopidogrel 1 Hr During Cangrelor Clopidogrel 600 mg administered orally 1 hr after the initiation of cangrelor infusion on Day 1. |
Drug: Cangrelor
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.
Drug: Clopidogrel
Clopidogrel 600 mg single oral dose
|
Outcome Measures
Primary Outcome Measures
- Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone [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]
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).
- Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone [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]
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).
Secondary Outcome Measures
- 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 [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]
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.
- 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 [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]
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 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 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 cAMP. Platelet reactivity was expressed in PRU.
- Bleeding Events In Accordance With GUSTO Scale [Screening through the follow-up period (5 to 7 days after Day 1)]
Bleeding was assessed by history, physical exam, and complete blood count (CBC) that was performed on study Day 1. Reports of bleeding were to be evaluated by performance of a CBC. Participants were assessed for bleeding events in accordance with the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) scale. The severity of bleeding events by GUSTO Criteria is defined as the following: Severe/life-threatening: fatal, intracranial hemorrhage, or if hemodynamic compromise results Moderate: transfusion required Mild: no transfusion or hemodynamic compromise A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Eligibility Criteria
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:
-
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 or coronary artery bypass graft, and
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fletcher Allen Health Care | Burlington | Vermont | United States | 05401 |
Sponsors and Collaborators
- The Medicines Company
Investigators
- Principal Investigator: David J. Schneider, MD, University of Vermont Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MDCO-CAN-13-02
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Prasugrel 30 Min After Cangrelor | Clopidogrel Within 5 Min After Cangrelor | Clopidogrel 1.5 Hrs During Cangrelor | Clopidogrel 1 Hr During Cangrelor |
|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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. | 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. |
| Period Title: Overall Study | ||||
| STARTED | 3 | 3 | 6 | 3 |
| Received at Least 1 Dose of Study Drug | 3 | 3 | 6 | 3 |
| ITT Population | 3 | 3 | 6 | 3 |
| COMPLETED | 3 | 3 | 6 | 3 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Prasugrel | Clopidogrel | Total |
|---|---|---|---|
| Arm/Group Description | 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. | Cangrelor IV was administered on Day 1 as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs on Day 1. Clopidogrel 600 mg was administered on Day 1 as a single oral dose 1 and 1.5 hrs after the initiation of cangrelor infusion and within 5 min after the discontinuation of the cangrelor infusion. | Total of all reporting groups |
| Overall Participants | 3 | 12 | 15 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
62.3
(6.66)
|
65.3
(6.18)
|
64.7
(6.15)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
0
0%
|
0
0%
|
| Male |
3
100%
|
12
100%
|
15
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
3
100%
|
12
100%
|
15
100%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
3
100%
|
12
100%
|
15
100%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | |||
| United States |
3
100%
|
12
100%
|
15
100%
|
Outcome Measures
| Title | Extent of Preservation Of Platelet Inhibitory Effect After Transition From Cangrelor To Prasugrel Or Clopidogrel Compared With Effect Observed With Prasugrel Or Clopidogrel Alone |
|---|---|
| Description | 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). |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants treated with cangrelor and prasugrel or clopidogrel were used for the analysis and presentation of data. |
| Arm/Group Title | Prasugrel 30 Min After Cangrelor | Clopidogrel Within 5 Min After Cangrelor | Clopidogrel 1.5 Hrs During Cangrelor | Clopidogrel 1 Hr During Cangrelor |
|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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. | 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. |
| Measure Participants | 3 | 3 | 6 | 3 |
| Prasugrel/Clopidogrel Reference (6 or 5.5 hrs) |
1.3
(1.5)
|
21.7
(16.4)
|
50.0
(16.8)
|
50.3
(15.9)
|
| 2.25 hrs |
16.3
(10.1)
|
26.0
(7.9)
|
22.2
(16.0)
|
33.3
(7.5)
|
| 2.5 hrs |
60.0
(7.5)
|
49.7
(7.1)
|
54.3
(11.7)
|
62.0
(3.6)
|
| 2.75 hrs |
63.3
(1.5)
|
58.3
(7.4)
|
56.8
(11.3)
|
67.7
(1.2)
|
| 3 hrs |
65.0
(2.0)
|
56.0
(8.9)
|
56.2
(16.4)
|
65.0
(9.5)
|
| 4 hrs |
16.3
(27.4)
|
38.0
(31.7)
|
51.2
(27.4)
|
62.7
(8.5)
|
| 5.5 hrs |
1.3
(1.5)
|
26.7
(20.5)
|
NA
(NA)
|
NA
(NA)
|
| Title | Extent Of Preservation Of Platelet Inhibitory Effect Of Cangrelor Treatment After Prasugrel Or Clopidogrel Compared To Treatment With Cangrelor Alone |
|---|---|
| Description | 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). |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants treated with cangrelor and prasugrel or clopidogrel were used for the analysis and presentation of data. |
| Arm/Group Title | Prasugrel 30 Min After Cangrelor | Clopidogrel Within 5 Min After Cangrelor | Clopidogrel 1.5 Hrs During Cangrelor | Clopidogrel 1 Hr During Cangrelor |
|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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. | Clopidogrel 600 mg was administered on Day 1 as a single oral dose 1 hr following the initiation of cangrelor infusion. Cangrelor IV was administered on Day 1 as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs. |
| Measure Participants | 3 | 3 | 6 | 3 |
| Cangrelor Reference (2.5, 2, 1.5, or 1 hrs) |
60.0
(7.5)
|
0
(0)
|
2.0
(3.5)
|
3.0
(2.0)
|
| 1.75 hrs |
0.3
(0.6)
|
1.0
(1.0)
|
1.8
(2.5)
|
1.3
(0.6)
|
| 2 hrs |
0.3
(0.6)
|
NA
(NA)
|
1.5
(2.0)
|
2.3
(1.2)
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants treated with cangrelor and prasugrel or clopidogrel were used for the analysis and presentation of data. |
| Arm/Group Title | Prasugrel 30 Min After Cangrelor | Clopidogrel Within 5 Min Post Cangrelor | Clopidogrel 1.5 Hrs During Cangrelor | Clopidogrel 1 Hr During Cangrelor |
|---|---|---|---|---|
| Arm/Group Description | 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). | 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). | 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 administered on Day 1 as a single oral dose 1.5 hrs following the initiation of cangrelor infusion. | 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. |
| Measure Participants | 3 | 3 | 6 | 3 |
| Prasugrel/Clopidogrel Reference (6 or 5.5 hrs) |
8.0
(8.7)
|
159.0
(72.7)
|
211.3
(66.8)
|
197.3
(15.0)
|
| 2.25 hrs |
76.7
(23.7)
|
99.0
(27.6)
|
90.3
(32.3)
|
98.7
(19.6)
|
| 2.5 hrs |
208.0
(30.2)
|
220.7
(11.6)
|
229.8
(24.6)
|
206.3
(26.9)
|
| 2.75 hrs |
225.7
(42.5)
|
233.0
(21.7)
|
255.8
(43.7)
|
214.3
(11.9)
|
| 3 hrs |
226.0
(28.5)
|
215.7
(35.0)
|
234.5
(34.2)
|
212.7
(10.3)
|
| 4 hrs |
77.0
(126.5)
|
182.0
(82.3)
|
215.5
(67.4)
|
203.7
(11.2)
|
| 5.5 hrs |
24.5
(34.6)
|
155.0
(69.8)
|
NA
(NA)
|
NA
(NA)
|
| Title | 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 |
|---|---|
| Description | 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 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 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 cAMP. Platelet reactivity was expressed in PRU. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants treated with cangrelor and prasugrel or clopidogrel were used for the analysis and presentation of data. |
| Arm/Group Title | Prasugrel 30 Min After Cangrelor | Clopidogrel Within 5 Min After Cangrelor | Clopidogrel 1.5 Hrs During Cangrelor | Clopidogrel 1 Hr During Cangrelor |
|---|---|---|---|---|
| Arm/Group Description | Prasugrel 60 mg was administered orally 30 min after the discontinuation of cangrelor infusion (2.5 hrs after initiation of cangrelor infusion). Cangrelor IV was administered as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs on study Day 1. | Clopidogrel 600 mg was administered orally within 5 min after the discontinuation of the cangrelor infusion (2 hrs after initiation of cangrelor infusion). Cangrelor IV was administered as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs on study Day 1. | Clopidogrel 600 mg administered orally 1.5 hrs following the initiation of cangrelor infusion. Cangrelor IV was administered as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs on study Day 1. | Clopidogrel 600 mg administered orally 1 hr following the initiation of cangrelor infusion. Cangrelor IV was administered as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs on study Day 1. |
| Measure Participants | 3 | 3 | 6 | 3 |
| Cangrelor Reference (2.5, 2, 1.5, or 1 hrs) |
208.0
(30.2)
|
7.3
(5.1)
|
17.7
(18.2)
|
7.0
(2.0)
|
| 1.75 hrs |
3.3
(2.3)
|
3.7
(2.1)
|
25.0
(30.5)
|
6.3
(1.5)
|
| 2 hrs |
5.3
(2.1)
|
NA
(NA)
|
28.8
(18.2)
|
5.7
(2.1)
|
| Title | Bleeding Events In Accordance With GUSTO Scale |
|---|---|
| Description | Bleeding was assessed by history, physical exam, and complete blood count (CBC) that was performed on study Day 1. Reports of bleeding were to be evaluated by performance of a CBC. Participants were assessed for bleeding events in accordance with the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) scale. The severity of bleeding events by GUSTO Criteria is defined as the following: Severe/life-threatening: fatal, intracranial hemorrhage, or if hemodynamic compromise results Moderate: transfusion required Mild: no transfusion or hemodynamic compromise A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Time Frame | Screening through the follow-up period (5 to 7 days after Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population included all participants who received at least 1 dose of study drug. |
| Arm/Group Title | Prasugrel 30 Min After Cangrelor | Clopidogrel Within 5 Min After Cangrelor | Clopidogrel 1.5 Hrs During Cangrelor | Clopidogrel 1 Hr During Cangrelor |
|---|---|---|---|---|
| Arm/Group Description | 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). Cangrelor IV was administered on Day 1 as a 30 μg/kg bolus, followed by 4 μg/kg/min infusion for 2 hrs. | 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). | 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. | 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. |
| Measure Participants | 3 | 3 | 6 | 3 |
| Mild |
0
|
0
|
0
|
0
|
| Moderate |
0
|
0
|
0
|
0
|
| Life-threatening/Severe |
0
|
0
|
0
|
0
|
Adverse Events
| Time Frame | Screening through the follow-up period (5 to 7 days after Day 1) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Prasugrel 30 Min After Cangrelor | Clopidogrel Within 5 Min After Cangrelor | Clopidogrel 1.5 Hrs During Cangrelor | Clopidogrel 1 Hr During Cangrelor | ||||
| Arm/Group Description | 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). | 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). | 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. | 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 administered on Day 1 as a single oral dose 1 hr following the initiation of cangrelor infusion. | ||||
All Cause Mortality |
||||||||
| Prasugrel 30 Min After Cangrelor | Clopidogrel Within 5 Min After Cangrelor | Clopidogrel 1.5 Hrs During Cangrelor | Clopidogrel 1 Hr During Cangrelor | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/3 (0%) | ||||
Serious Adverse Events |
||||||||
| Prasugrel 30 Min After Cangrelor | Clopidogrel Within 5 Min After Cangrelor | Clopidogrel 1.5 Hrs During Cangrelor | Clopidogrel 1 Hr During Cangrelor | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/3 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Prasugrel 30 Min After Cangrelor | Clopidogrel Within 5 Min After Cangrelor | Clopidogrel 1.5 Hrs During Cangrelor | Clopidogrel 1 Hr During Cangrelor | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/3 (0%) | 0/6 (0%) | 0/3 (0%) | ||||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Global Health Science Center, The Medicines Company |
|---|---|
| Organization | The Medicines Company |
| Phone | 1-888-977-6326 |
| medical.information@themedco.com |
- MDCO-CAN-13-02