Trial in Subjects Undergoing Cardiac Catheterization With Planned Percutaneous Coronary Intervention With Stenting

Coronary Artery Disease Clinical Trial

— PRINCIPLE  

Official title:

Protocol H7T-MC-TABL(a) PRasugrel IN Comparison to Clopidogrel for Inhibition of PLatelet Activation and AggrEgation (PRINCIPLE) - TIMI 44

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00357968
• Other study ID #: 10635
• Secondary ID: H7T-MC-TABL
• Status: Completed
• Phase: Phase 2
• First received: July 26, 2006
• Last updated: August 25, 2010
• Start date: August 2006
• Est. completion date: June 2007

Study information

• Verified date: August 2010
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 201
• Est. completion date: June 2007
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Prasugrel
Administered orally
• Clopidogrel
Administered orally
• Placebo for Prasugrel
Administered orally
• Placebo for Clopidogrel
Administered orally

Locations

Country	Name	City	State
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	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	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	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
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	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	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	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	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
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	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	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
United States	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	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	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	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

Sponsors (3)

Lead Sponsor	Collaborator
Eli Lilly and Company	Daiichi Sankyo Inc., The TIMI Study Group

Countries where clinical trial is conducted

United States,  France,  Germany,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inhibition of Platelet Aggregation (IPA) to 20 Micromolar (µM) Adenosine Diphosphate (ADP) at 6 Hours After the Loading Dose	IPA was defined as (1 - [maximal platelet aggregation(MPA) at 6 hours after study drug treatment]/[MPA before drug treatment]) x 100.	6 hours after loading dose	No
Primary	Inhibition of Platelet Aggregation to 20 µM Adenosine Diphosphate After 14 Days of Maintenance Dose Treatment	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.	after 14 days of maintenance dosing	No
Secondary	Inhibition of Platelet Aggregation to 20 µM Adenosine Diphosphate at 2 Hours After the Loading Dose	IPA was defined as (1 - [maximal platelet aggregation (MPA) at 2 hours after study drug treatment]/[MPA before drug treatment]) x 100.	2 hours after loading dose	No
Secondary	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	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.	after 14 days of treatment (before cross-over)	Yes
Secondary	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	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.	14 days after cross-over	Yes
Secondary	Number of Participants With Major Adverse Cardiac Events (MACE) During the First Maintenance Dose Phase	Number of patients who met any of the following endpoints: cardiovascular death, myocardial infarction, stroke, subacute stent thrombosis, or urgent target vessel revascularization	after 14 days of treatment (before cross-over)	No
Secondary	Number of Participants With Major Adverse Cardiac Events During the Crossover Maintenance Dose Phase	Number of patients who met any of the following endpoints: cardiovascular death, myocardial infarction, stroke, subacute stent thrombosis, or urgent target vessel revascularization	14 days after cross-over	No
Secondary	Number of Hyporesponsive Participants at 6 Hours After the Loading Dose	Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) <20%	6 hours after loading dose	No
Secondary	Number of Hyporesponsive Participants at the End of the First Maintenance Dose Phase	Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) <20%	From loading dose to day 15	No
Secondary	Number of Hyporesponsive Participants at the End of the Crossover Maintenance Dose Phase	Number of patients with inhibition of platelet aggregation (IPA) with 20 uM adenosine diphosphate (ADP) <20%	14 days after cross-over	No
Secondary	Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 2 Hours After the Loading Dose	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.	2 hours after loading dose	No
Secondary	Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) at 6 Hours After the Loading Dose	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.	6 hours after loading dose	No
Secondary	Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) 18 to 24 Hours After the Loading Dose	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.	18 to 24 hours after loading dose	No
Secondary	Platelet Reactivity Index Percent (PRI%) Measured by Vasodilator-stimulated Phosphoprotein (VASP) After 14 Days of Maintenance Dose Treatment	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.	after 14 days of maintenance dosing	No
Secondary	Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) at 6 Hours After the Loading Dose	Mean CK-MB at 6 hours after loading dose. CK-MB is a biomarker for myonecrosis	6 hours after loading dose	No
Secondary	Myonecrosis Measure: Creatine Kinase-Myocardial Bands (CK-MB) 18 to 24 Hours After the Loading Dose	Mean CK-MB at 18-24 hours after loading dose. CK-MB is a biomarker for myonecrosis.	18 to 24 hours after loading dose	No
Secondary	Myonecrosis Measure: Cardiac Troponin at 6 Hours After the Loading Dose	Mean troponin level at 6 hours after the loading dose. Troponin is a biomarker for myonecrosis.	6 hours after loading dose	No
Secondary	Myonecrosis Measure: Cardiac Troponin 18 to 24 Hours After the Loading Dose	Mean troponin level at 18 to 24 hours after the loading dose. Troponin is a biomarker for myonecrosis.	18 to 24 hours after loading dose	No

External Links

•   Lilly Clinical Trial Registry