A Study of the Antiplatelet Effects Comparing Ticagrelor (Ticag. - AZD6140) With Clopidogrel (Clop.) Responder and Non-responders - Full Text View

Sponsor:	AstraZeneca
Information provided by (Responsible Party):	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00642811

Purpose

The purpose of this study is to see how Ticagrelor, a new oral reversible anti-platelet medication, affects platelets. Anti-platelet agents are medications that block the formation of blood clots by preventing the clumping of platelets. Blood clots prevent us from bleeding, but when they form inside the arteries their formation is linked to a risk of medical problems such as heart attack and stroke. This study investigated the effect of Ticagrelor on inhibition of platelet aggregation compared with clopidogrel in patients previously identified as non-responsive to clopidogrel.

Condition	Intervention	Phase
Stable Coronary Artery Disease	Drug: Ticagrelor Drug: Clopidogrel Drug: Aspirin	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomised, Double-Blind, Outpatient, Crossover Study of the Anti-platelet Effects of Ticagrelor Compared With Clopidogrel in Patients With Stable Coronary Artery Disease Previously Identified as Clopidogrel Non-responders or Responders [RESPOND]

Resource links provided by NLM:

MedlinePlus related topics: Coronary Artery Disease

Drug Information available for: Acetylsalicylic acid Clopidogrel Clopidogrel Bisulfate

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Proportion of Clopidogrel Non-responders Who Responded to Clopidogrel or Ticagrelor. - Comparing Ticag. (Day 28 of Clop. to Ticag., and Day 14 of Ticag. to Clop.) Versus Clop. (Day 14 of Clop. to Ticag., and Day 28 of Ticag. to Clop.) [ Time Frame: Day 14 and Day 28, 4 Hrs Post Dose. ] [ Designated as safety issue: No ]
The primary definition of response to treatment is IPA >10% post treatment. The response is reported as percentage of participants of each treatment. Please refer to the protocol section for details about the interventions administered. IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.
Proportion of Clopidogrel Non-responders Who Responded to Clopidogrel or Ticagrelor. - Comparing Ticag. (Day 28 of Clop. to Ticag., and Day 14 of Ticag. to Clop.) Versus Clop. (Day 14 of Clop. to Ticag., and Day 28 of Ticag. to Clop. [ Time Frame: Day 14, and day 28, 4 hours post dose ] [ Designated as safety issue: No ]
The secondary definition of response to treatment is IPA >50% post treatment. The response is reported as percentage of participants of each treatment. Please refer to the protocol section for details about the interventions administered. IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.

Secondary Outcome Measures:

Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 15 [ Time Frame: Day 15, 4 hrs post switching ] [ Designated as safety issue: No ]
IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition. Please refer to the protocol section for details about the interventions administered.
Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 28 [ Time Frame: 4 hrs post first dose on day 28 ] [ Designated as safety issue: No ]
IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition. Please refer to the protocol section for details about the interventions administered.
Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 15 [ Time Frame: Day 15, 4 hrs post switching ] [ Designated as safety issue: No ]
IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition. Please refer to the protocol section for details about the interventions administered.
Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 28 [ Time Frame: 4 hrs post first dose on day 28 ] [ Designated as safety issue: No ]
IPA(%)=(PAb-PAt)/PAb*100. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition. Please refer to the protocol section for details about the interventions administered.

Enrollment:	98
Study Start Date:	May 2008
Study Completion Date:	March 2009
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Aspirin + Ticagrelor	Drug: Ticagrelor Tablets, Oral, 90 mg; 180 mg loading dose followed by 90 mg twice daily for 2 weeks Drug: Aspirin Tablets, Oral, 75 mg to 100 mg once daily. Aspirin obtained locally by the investigator, according to local practice. The dose remained constant throughout the study
Active Comparator: 2 Aspirin + Clopidogrel	Drug: Clopidogrel (over encapsulated) capsule, Oral, 75 mg; 600 mg loading dose followed by 75 mg once daily for 2 weeks Other Name: Plavix Drug: Aspirin Tablets, Oral, 75 mg to 100 mg once daily. Aspirin obtained locally by the investigator, according to local practice. The dose remained constant throughout the study

Eligibility

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

Criteria

Inclusion Criteria:

Patients with documented stable Coronary Artery Disease (CAD) (stable angina, previous MI history, previous history of revascularization)
Females of child bearing potential must have a negative pregnancy test prior to receiving study drug and be willing to use a hormonal contraceptive in addition to double barrier contraception

Exclusion Criteria:

History of Acute Coronary Syndromes within 12 months of screening or need for revascularization (angioplasty or coronary artery bypass graft (CABG))
Any acute or chronic unstable condition in the past 30 days
Have increased bleeding risk, eg, recent gastrointestinal bleed, uncontrolled high blood pressure, low platelet count, recent major trauma
History of intolerance or allergy to aspirin or clopidogrel

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00642811

Locations

United States, Arkansas
Research Site
Jonesboro, Arkansas, United States
United States, Florida
Research Site
Ormond Beach, Florida, United States
United States, Maryland
Research Site
Baltimore, Maryland, United States
United States, Ohio
Research Site
Cincinnati, Ohio, United States
Canada, Ontario
Research Site
Hamilton, Ontario, Canada
Canada
Research Site
Lachine, Canada
Denmark
Research Site
Aalborg, Denmark
Research Site
Arhus, Denmark
Research Site
Esbjerg, Denmark
United Kingdom
Research Site
Sheffield, United Kingdom

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:	Jay Horrow, MD	AstraZeneca
Principal Investigator:	Paul Gurbel, md	Platelet & Thrombosis Research, LLC

More Information

No publications provided by AstraZeneca

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

Tantry US, Bliden KP, Wei C, Storey RF, Armstrong M, Butler K, Gurbel PA. First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus clopidogrel: the ONSET/OFFSET and RESPOND genotype studies. Circ Cardiovasc Genet. 2010 Dec 1;3(6):556-66. Epub 2010 Nov 15.

Gurbel PA, Bliden KP, Butler K, Antonino MJ, Wei C, Teng R, Rasmussen L, Storey RF, Nielsen T, Eikelboom JW, Sabe-Affaki G, Husted S, Kereiakes DJ, Henderson D, Patel DV, Tantry US. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation. 2010 Mar 16;121(10):1188-99. Epub 2010 Mar 1.

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00642811 History of Changes
Other Study ID Numbers:	D5130C00030
Study First Received:	March 19, 2008
Results First Received:	January 27, 2011
Last Updated:	August 30, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by AstraZeneca:

coronary artery disease (CAD)
heart attack
stable angina

Additional relevant MeSH terms:

Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Aspirin
Ticlopidine
Clopidogrel
Ticagrelor
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics

Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012