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

Stable Coronary Artery Disease Clinical Trial

— RESPOND  

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]

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00642811
• Other study ID #: D5130C00030
• Status: Completed
• Phase: Phase 2
• First received: March 19, 2008
• Last updated: August 30, 2011
• Start date: May 2008
• Est. completion date: March 2009

Study information

• Verified date: August 2011
• Source: AstraZeneca
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics 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
• Stable Coronary Artery Disease

Intervention

Drug:
• Ticagrelor
Tablets, Oral, 90 mg; 180 mg loading dose followed by 90 mg twice daily for 2 weeks
• Clopidogrel
(over encapsulated) capsule, Oral, 75 mg; 600 mg loading dose followed by 75 mg once daily for 2 weeks
• 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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.)	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.	Day 14 and Day 28, 4 Hrs Post Dose.	No
Primary	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.	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.	Day 14, and day 28, 4 hours post dose	No
Secondary	Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 15	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.	Day 15, 4 hrs post switching	No
Secondary	Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 28	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.	4 hrs post first dose on day 28	No
Secondary	Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 15	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.	Day 15, 4 hrs post switching	No
Secondary	Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 28	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.	4 hrs post first dose on day 28	No