A Comparison of Prasugrel (CS-747) and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention - Full Text View

Sponsor:	Eli Lilly and Company
Collaborator:	Daiichi Sankyo Inc.
Information provided by:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00097591

Purpose

The sponsors of this investigational drug are developing prasugrel (also known as CS-747) as a possible treatment for patients with acute coronary syndrome (heart attack or chest pain) who need, or are expected to need, a percutaneous coronary intervention (PCI; also called a balloon angioplasty). Prasugrel was compared with Clopidogrel to determine which drug is better at reducing deaths, future heart attacks, or stroke.

Condition	Intervention	Phase
Coronary Arteriosclerosis Acute Coronary Syndromes	Drug: Prasugrel Drug: Clopidogrel	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Comparison of CS-747 and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention

Resource links provided by NLM:

MedlinePlus related topics: Coronary Artery Disease Heart Attack

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:

Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke [ Time Frame: Randomization up to 15 months ] [ Designated as safety issue: No ]
The endpoint in this measure is a combination of CV death, nonfatal MI, or nonfatal stroke. The data is presented by the study population, which is represented as follows: 1) subjects who presented with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI), 2) subjects who presented with ST segment elevation myocardial infarction (STEMI), and 3) all subjects with acute coronary syndromes (ACS) (i.e. all subjects with UA/NSTEMI or STEMI).

Secondary Outcome Measures:

Number of Treated Subjects With Non-Coronary Artery Bypass Graft (CABG) Related Thrombolysis In Myocardial Infarction (TIMI) Study Group Major and Minor Bleeding Events [ Time Frame: First dose of study drug up to 15 months (while at risk) ] [ Designated as safety issue: Yes ]
TIMI classification for major and minor bleeding in the subset of subjects who did not undergo a coronary artery bypass operation (CABG) were defined as follows: Major bleeding: any intracranial hemorrhage (ICH) OR any clinically overt bleeding (including bleeding evident on imaging studies) associated with a fall in hemoglobin (Hgb) of ≥5 grams/deciliter (gm/dL)from baseline. Minor Bleeding: any clinically overt bleeding associated with a fall in Hgb of ≥3 gm/dL but <5 gm/dL from baseline. Major bleeding events were further examined as events that were deemed life threatening and/or fatal.
Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Urgent Target Vessel Revascularization (UTVR) [ Time Frame: Randomization to 30 days; randomization to 90 days ] [ Designated as safety issue: No ]
The endpoint in this measure is a combination of CV death, nonfatal MI, or UTVR. Results are reported for the All ACS subject population for the 30 and 90 day periods.
Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke [ Time Frame: Randomization to 30 days; randomization to 90 days ] [ Designated as safety issue: No ]
The endpoint in this measure is a combination of CV death, nonfatal MI, or nonfatal stroke. Results are reported for the All ACS population for the 30 and 90 day periods.
Number of Subjects Reaching the Composite Endpoint of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, or Rehospitalization for Cardiac Ischemic Events [ Time Frame: Randomization up to 15 months ] [ Designated as safety issue: No ]
The endpoint in this measure is a combination of CV death, nonfatal MI, nonfatal stroke, or rehospitalization for cardiac ischemic events. Results are reported for the All ACS population.
Number of Subjects Reaching the Composite Endpoint of All-Cause Death, Nonfatal Myocardial Infarction (MI), or Nonfatal Stroke [ Time Frame: Randomization up to 15 months ] [ Designated as safety issue: No ]
The endpoint in this measure is a combination of all-cause death, nonfatal MI, or nonfatal stroke. Results are reported for the All ACS population.

Enrollment:	13619
Study Start Date:	November 2004
Study Completion Date:	July 2007
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Prasugrel Oral loading dose of six 10 mg prasugrel tablets and four placebo tablets matched to clopidogrel, followed by an oral maintenance dose of prasugrel one 10 mg tablet and one placebo tablet matched to clopidogrel once daily	Drug: Prasugrel Administered orally Other Names: CS-747 LY640315 Effient Efient
Active Comparator: Clopidogrel Oral loading dose of four 75 mg clopidogrel tablets and six placebo tablets matched to prasugrel, followed by an oral maintenance dose of one 75 mg clopidogrel tablet and one placebo tablet matched to prasugrel once daily	Drug: Clopidogrel Administered orally

Eligibility

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

Criteria

Inclusion Criteria:

A person who has been diagnosed with acute coronary syndrome and is to undergo a percutaneous coronary intervention.
A person who is of the legal age of 18 and is mentally competent to provide a signed written informed consent.
If a woman is of childbearing potential (i.e., before menopause), she must test negative for pregnancy and agree to use a reliable method of birth control.

Exclusion Criteria:

A person who has had an ischemic stroke within the last 3 months or a hemorrhagic stroke at any time in the past.
A person who has active internal bleeding or has a history of a bleeding disorder.
Individuals who are at an increased risk of bleeding based on laboratory criteria evaluated by the treatment physician or on medication that can cause bleeding.
A person who has liver disease; for example, cirrhosis.
A person who has a condition such as alcoholism, mental illness, or is drug dependent.
A person who has cardiogenic shock, a refractory ventricular arrhythmia, or congestive heart failure (class IV).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00097591

Locations

United States, Indiana
For more information regarding investigative sites for this trial, call 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri 9 AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST), Global Quintiles Study Line (1-866-615-4672) or speak with your physician
Indianapolis, Indiana, United States

Sponsors and Collaborators

Eli Lilly and Company

Daiichi Sankyo Inc.

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

Publications:

Pride YB, Tung P, Mohanavelu S, Zorkun C, Wiviott SD, Antman EM, Giugliano R, Braunwald E, Gibson CM; TIMI Study Group. Angiographic and clinical outcomes among patients with acute coronary syndromes presenting with isolated anterior ST-segment depression: a TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) substudy. JACC Cardiovasc Interv. 2010 Aug;3(8):806-11.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hochholzer W, Wiviott SD, Antman EM, Contant CF, Guo J, Giugliano RP, Dalby AJ, Montalescot G, Braunwald E. Predictors of bleeding and time dependence of association of bleeding with mortality: insights from the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel--Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38). Circulation. 2011 Jun 14;123(23):2681-9. Epub 2011 May 23.

Mahoney EM, Wang K, Arnold SV, Proskorovsky I, Wiviott S, Antman E, Braunwald E, Cohen DJ. Cost-effectiveness of prasugrel versus clopidogrel in patients with acute coronary syndromes and planned percutaneous coronary intervention: results from the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with Prasugrel-Thrombolysis in Myocardial Infarction TRITON-TIMI 38. Circulation. 2010 Jan 5;121(1):71-9. Epub 2009 Dec 21.

Pride YB, Wiviott SD, Buros JL, Zorkun C, Tariq MU, Antman EM, Braunwald E, Gibson CM; TIMI Study Group. Effect of prasugrel versus clopidogrel on outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention without stent implantation: a TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel (TRITON)-Thrombolysis in Myocardial Infarction (TIMI) 38 substudy. Am Heart J. 2009 Sep;158(3):e21-6.

Montalescot G, Wiviott SD, Braunwald E, Murphy SA, Gibson CM, McCabe CH, Antman EM; TRITON-TIMI 38 investigators. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet. 2009 Feb 28;373(9665):723-31.

Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009 Jan 22;360(4):354-62. Epub 2008 Dec 22.

Wiviott SD, Braunwald E, Angiolillo DJ, Meisel S, Dalby AJ, Verheugt FW, Goodman SG, Corbalan R, Purdy DA, Murphy SA, McCabe CH, Antman EM; TRITON-TIMI 38 Investigators. Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial Infarction 38. Circulation. 2008 Oct 14;118(16):1626-36. Epub 2008 Aug 31.

Antman EM, Wiviott SD, Murphy SA, Voitk J, Hasin Y, Widimsky P, Chandna H, Macias W, McCabe CH, Braunwald E. Early and late benefits of prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis. J Am Coll Cardiol. 2008 May 27;51(21):2028-33.

Wiviott SD, Braunwald E, McCabe CH, Horvath I, Keltai M, Herrman JP, Van de Werf F, Downey WE, Scirica BM, Murphy SA, Antman EM; TRITON-TIMI 38 Investigators. Intensive oral antiplatelet therapy for reduction of ischaemic events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous coronary intervention and stenting in the TRITON-TIMI 38 trial: a subanalysis of a randomised trial. Lancet. 2008 Apr 19;371(9621):1353-63. Epub 2008 Apr 2.

Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001-15. Epub 2007 Nov 4.

Responsible Party:	Chief Medical Officer, Eli LIlly
ClinicalTrials.gov Identifier:	NCT00097591 History of Changes
Other Study ID Numbers:	8695, H7T-MC-TAAL
Study First Received:	November 24, 2004
Results First Received:	April 19, 2010
Last Updated:	August 25, 2010
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Arteriosclerosis
Coronary Artery Disease
Myocardial Ischemia
Acute Coronary Syndrome
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Coronary Disease
Heart Diseases
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms
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