Trial in Subjects Undergoing Cardiac Catheterization With Planned Percutaneous Coronary Intervention With Stenting - Full Text View

Sponsor:	Eli Lilly and Company
Collaborators:	Daiichi Sankyo Inc. The TIMI Study Group
Information provided by:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00357968

Purpose

The purpose of this study is to provide information of the relative potency of prasugrel and clopidogrel on platelet function studies, inflammation, and myocyte necrosis in subjects undergoing elective percutaneous coronary intervention (PCI).

Condition	Intervention	Phase
Coronary Artery Disease	Drug: Prasugrel Drug: Clopidogrel Drug: Placebo for Prasugrel Drug: Placebo for Clopidogrel	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Protocol H7T-MC-TABL(a) PRasugrel IN Comparison to Clopidogrel for Inhibition of PLatelet Activation and AggrEgation (PRINCIPLE) - TIMI 44

Resource links provided by NLM:

MedlinePlus related topics: Coronary Artery Disease

Drug Information available for: Clopidogrel Clopidogrel Bisulfate Prasugrel

U.S. FDA Resources

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Inhibition of Platelet Aggregation (IPA) to 20 Micromolar (μM) Adenosine Diphosphate (ADP) at 6 Hours After the Loading Dose [ Time Frame: 6 hours after loading dose ] [ Designated as safety issue: No ]
IPA was defined as (1 - [maximal platelet aggregation(MPA) at 6 hours after study drug treatment]/[MPA before drug treatment]) x 100.
Inhibition of Platelet Aggregation to 20 μM Adenosine Diphosphate After 14 Days of Maintenance Dose Treatment [ Time Frame: after 14 days of maintenance dosing ] [ Designated as safety issue: No ]
Measures IPA during maintenance dosing before and after cross-over for each therapy.

IPA was defined as (1 - [maximal platelet aggregation(MPA) at 14 days after study drug treatment]/[MPA before drug treatment]) x 100.

Secondary Outcome Measures:

Inhibition of Platelet Aggregation to 20 μM Adenosine Diphosphate at 2 Hours After the Loading Dose [ Time Frame: 2 hours after loading dose ] [ Designated as safety issue: No ]
IPA was defined as (1 - [maximal platelet aggregation (MPA) at 2 hours after study drug treatment]/[MPA before drug treatment]) x 100.
Number of Participants With Non-Coronary Artery Bypass Graft (CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding During the First Maintenance Dose Phase [ Time Frame: after 14 days of treatment (before cross-over) ] [ Designated as safety issue: Yes ]
Non-CABG-related TIMI major bleeding was any intracranial hemorrhage OR any clinically overt bleeding associated with a fall in hemoglobin >=5 gm/dL.

Non-CABG-related TIMI minor bleeding was any clinically overt bleeding associated with a fall in hemoglobin >=3 gm/dL but <5 gm/dL.
Number of Participants With Non-Coronary Artery Bypass Graft (CABG) Thrombolysis in Myocardial Infarction (TIMI) Major or Minor Bleeding During the Crossover Maintenance Dose Phase [ Time Frame: 14 days after cross-over ] [ Designated as safety issue: Yes ]
Non-CABG-related TIMI major bleeding was any intracranial hemorrhage OR any clinically overt bleeding associated with a fall in hemoglobin >=5 gm/dL.

Non-CABG-related TIMI minor bleeding was any clinically overt bleeding associated with a fall in hemoglobin >=3 gm/dL but <5 gm/dL.
Number of Participants With Major Adverse Cardiac Events (MACE) During the First Maintenance Dose Phase [ Time Frame: after 14 days of treatment (before cross-over) ] [ Designated as safety issue: No ]
Number of patients who met any of the following endpoints: cardiovascular death, myocardial infarction, stroke, subacute stent thrombosis, or urgent target vessel revascularization
Number of Participants With Major Adverse Cardiac Events During the Crossover Maintenance Dose Phase [ Time Frame: 14 days after cross-over ] [ Designated as safety issue: No ]
Number of patients who met any of the following endpoints: cardiovascular death, myocardial infarction, stroke, subacute stent thrombosis, or urgent target vessel revascularization
Number of Hyporesponsive Participants at 6 Hours After the Loading Dose [ Time Frame: 6 hours after loading dose ] [ Designated as safety issue: No ]
Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) <20%
Number of Hyporesponsive Participants at the End of the First Maintenance Dose Phase [ Time Frame: From loading dose to day 15 ] [ Designated as safety issue: No ]
Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) <20%
Number of Hyporesponsive Participants at the End of the Crossover Maintenance Dose Phase [ Time Frame: 14 days after cross-over ] [ Designated as safety issue: No ]
Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) <20%
Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 2 Hours After the Loading Dose [ Time Frame: 2 hours after loading dose ] [ Designated as safety issue: No ]
VASP phosphorylation in response to prostaglandin E1 (PGE1) with and without ADP was determined by whole-blood flow cytometry and was expressed as a platelet reactivity index (PRI). PRI was defined as [(MFI(with PGE1) - MFI (with PGE1 and ADP))/MFI(with PGE1) x 100] where MFI is mean fluorescence index. A lower PRI indicates greater antiplatelet effect.
Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 6 Hours After the Loading Dose [ Time Frame: 6 hours after loading dose ] [ Designated as safety issue: No ]
VASP phosphorylation in response to prostaglandin E1 (PGE1) with and without ADP was determined by whole-blood flow cytometry and was expressed as a platelet reactivity index (PRI). PRI was defined as [(MFI(with PGE1) - MFI (with PGE1 and ADP))/MFI(with PGE1) x 100] where MFI is mean fluorescence index. A lower PRI indicates greater antiplatelet effect.
Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) 18 to 24 Hours After the Loading Dose [ Time Frame: 18 to 24 hours after loading dose ] [ Designated as safety issue: No ]
VASP phosphorylation in response to prostaglandin E1 (PGE1) with and without ADP was determined by whole-blood flow cytometry and was expressed as a platelet reactivity index (PRI). PRI was defined as [(MFI(with PGE1) - MFI (with PGE1 and ADP))/MFI(with PGE1) x 100] where MFI is mean flourescence index. A lower PRI indicates greater antiplatelet effect.
Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) After 14 Days of Maintenance Dose Treatment [ Time Frame: after 14 days of maintenance dosing ] [ Designated as safety issue: No ]
VASP phosphorylation in response to prostaglandin E1 (PGE1) with and without ADP was determined by whole-blood flow cytometry and was expressed as a platelet reactivity index (PRI). PRI was defined as [(MFI(with PGE1) - MFI (with PGE1 and ADP))/MFI(with PGE1) x 100] where MFI is mean fluorescence index. A lower PRI indicates greater antiplatelet effect.
Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) at 6 Hours After the Loading Dose [ Time Frame: 6 hours after loading dose ] [ Designated as safety issue: No ]
Mean CK-MB at 6 hours after loading dose. CK-MB is a biomarker for myonecrosis
Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) 18 to 24 Hours After the Loading Dose [ Time Frame: 18 to 24 hours after loading dose ] [ Designated as safety issue: No ]
Mean CK-MB at 18-24 hours after loading dose. CK-MB is a biomarker for myonecrosis.
Myonecrosis Measure: Cardiac Troponin at 6 Hours After the Loading Dose [ Time Frame: 6 hours after loading dose ] [ Designated as safety issue: No ]
Mean troponin level at 6 hours after the loading dose. Troponin is a biomarker for myonecrosis.
Myonecrosis Measure: Cardiac Troponin 18 to 24 Hours After the Loading Dose [ Time Frame: 18 to 24 hours after loading dose ] [ Designated as safety issue: No ]
Mean troponin level at 18 to 24 hours after the loading dose. Troponin is a biomarker for myonecrosis.

Enrollment:	201
Study Start Date:	August 2006
Study Completion Date:	June 2007
Primary Completion Date:	June 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Prasugrel to Clopidogrel One time oral loading dose (LD) of 60-mg Prasugrel and placebo matched to clopidogrel (plus oral enteric coated aspirin 325 mg to 500 mg is recommended) followed by 10-mg Prasugrel and placebo matched to clopidogrel taken orally once a day for 14 days. Patients cross-over to 150 mg clopidogrel and placebo matched to prasugrel taken orally once a day for the next 14 days.	Drug: Prasugrel Administered orally Other Names: LY 640315 Effient Efient Drug: Clopidogrel Administered orally Drug: Placebo for Prasugrel Administered orally Drug: Placebo for Clopidogrel Administered orally
Active Comparator: Clopidogrel to Prasugrel One time oral LD of 600 mg clopidogrel and placebo matched to prasugrel (plus oral enteric coated aspirin 325 mg to 500 mg is recommended) followed by 150 mg clopidogrel and placebo matched to prasugrel taken orally once a day for 14 days. Patients cross-over to 10 mg prasugrel and placebo tablets matched to clopidogrel taken orally once a day for the next 14 days.	Drug: Prasugrel Administered orally Other Names: LY 640315 Effient Efient Drug: Clopidogrel Administered orally Drug: Placebo for Prasugrel Administered orally Drug: Placebo for Clopidogrel Administered orally

Arms

Assigned Interventions

Experimental: Prasugrel to Clopidogrel

One time oral loading dose (LD) of 60-mg Prasugrel and placebo matched to clopidogrel (plus oral enteric coated aspirin 325 mg to 500 mg is recommended) followed by 10-mg Prasugrel and placebo matched to clopidogrel taken orally once a day for 14 days. Patients cross-over to 150 mg clopidogrel and placebo matched to prasugrel taken orally once a day for the next 14 days.

Drug: Prasugrel

Administered orally

Other Names:

LY 640315
Effient
Efient

Drug: Clopidogrel

Administered orally

Drug: Placebo for Prasugrel

Administered orally

Drug: Placebo for Clopidogrel

Administered orally

Active Comparator: Clopidogrel to Prasugrel

One time oral LD of 600 mg clopidogrel and placebo matched to prasugrel (plus oral enteric coated aspirin 325 mg to 500 mg is recommended) followed by 150 mg clopidogrel and placebo matched to prasugrel taken orally once a day for 14 days. Patients cross-over to 10 mg prasugrel and placebo tablets matched to clopidogrel taken orally once a day for the next 14 days.

Drug: Prasugrel

Administered orally

Other Names:

LY 640315
Effient
Efient

Drug: Clopidogrel

Administered orally

Drug: Placebo for Prasugrel

Administered orally

Drug: Placebo for Clopidogrel

Administered orally

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects greater than or equal to 18 years of age undergoing cardiac catheterization with planned percutaneous coronary intervention (if coronary anatomy is suitable) for an indication of chest pain +/or anginal equivalent felt by the treating physician to be related to coronary ischemia.
At least one of the following (a through c):
1. Functional study (exercise, or pharmacologic) within the past 8 weeks consistent with ischemia as manifested by at least one of the following:
  1. A reversible defect on nuclear imaging.
  2. A reversible wall-motion abnormality by echocardiography.
  3. Horizontal or down-sloping ST-depressions greater than 1 mm on electrocardiogram (ECG) (if no imaging performed).
2. Prior coronary revascularization [percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)].
3. A cardiac catheterization with at least one coronary artery lesion amenable to PCI (not yet performed) within 14 days prior to enrollment.

Exclusion Criteria:

Known creatine kinase-myocardial bands (CK-MB)or cardiac troponin greater than the upper limit of normal at time of screening
Planned PCI for acute myocardial infarction (MI) or planned PCI within 48 hours of fibrinolytic therapy for ST segment elevation myocardial infarction (STEMI)
Have cardiogenic shock at the time of screening (systolic blood pressure 90 mm Hg associated with clinical evidence of end-organ hypoperfusion, or subjects requiring vasopressors to maintain systolic blood pressure over 90 mm Hg and associated with clinical evidence of end-organ hypoperfusion).
Refractory ventricular arrhythmias
Have New York Heart Association Class IV congestive heart failure

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00357968

Locations

United States, Florida
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Jacksonville, Florida, United States, 32209
United States, Massachusetts
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Worcester, Massachusetts, United States, 01655
United States, Michigan
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Ann Arbor, Michigan, United States, 48109
United States, South Dakota
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Rapid City, South Dakota, United States, 57701
France
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Lille, France, 59037
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Marseille, France, 13385
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Paris, France, 75013
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Tours, France, 37044
Germany
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Bad Krozingen, Germany, D-79189
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Berlin, Germany, D-12203
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Giessen, Germany, 35392
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München, Germany, D-80636
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Tubingen, Germany, 72076
Israel
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Haifa, Israel, 31096
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Jerusalem, Israel, 91120
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Tel Hashomer, Israel, 52621

Sponsors and Collaborators

Eli Lilly and Company

Daiichi Sankyo Inc.

The TIMI Study Group

Investigators

Study Director:

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Eli Lilly and Company

More Information

Additional Information:

Lilly Clinical Trial Registry This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier:	NCT00357968 History of Changes
Other Study ID Numbers:	10635, H7T-MC-TABL
Study First Received:	July 26, 2006
Results First Received:	April 19, 2010
Last Updated:	August 25, 2010
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Clopidogrel
Ticlopidine
Prasugrel
Platelet Aggregation Inhibitors
Hematologic Agents

Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on February 09, 2012