Trial in Subjects Undergoing Cardiac Catheterization With Planned Percutaneous Coronary Intervention With Stenting (PRINCIPLE)
This study has been completed.
Sponsor:
Eli Lilly and Company
Collaborators:
Daiichi Sankyo Inc.
The TIMI Study Group
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00357968
First received: July 26, 2006
Last updated: August 25, 2010
Last verified: August 2010
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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 2 |
| 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 bisulfate
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:
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:
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):
Functional study (exercise, or pharmacologic) within the past 8 weeks consistent with ischemia as manifested by at least one of the following:
- A reversible defect on nuclear imaging.
- A reversible wall-motion abnormality by echocardiography.
- Horizontal or down-sloping ST-depressions greater than 1 mm on electrocardiogram (ECG) (if no imaging performed).
- Prior coronary revascularization [percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)].
- 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 | |
| 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. | |
| Rapid City, South Dakota, United States, 57701 | |
| France | |
| 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. | |
| Lille, France, 59037 | |
| 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. | |
| Marseille, France, 13385 | |
| 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. | |
| Paris, France, 75013 | |
| 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. | |
| Tours, France, 37044 | |
| Germany | |
| 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. | |
| Bad Krozingen, Germany, D-79189 | |
| 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. | |
| Berlin, Germany, D-12203 | |
| 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. | |
| Giessen, Germany, 35392 | |
| 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. | |
| München, Germany, D-80636 | |
| 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. | |
| Tubingen, Germany, 72076 | |
| Israel | |
| 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. | |
| Haifa, Israel, 31096 | |
| 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. | |
| 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:
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 May 23, 2013