Stable Coronary Artery Disease
Conditions
Keywords
coronary artery disease (CAD), heart attack, stable angina
Brief 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.
Interventions
DRUGTicagrelor
Tablets, Oral, 90 mg; 180 mg loading dose followed by 90 mg twice daily for 2 weeks
DRUGClopidogrel
(over encapsulated) capsule, Oral, 75 mg; 600 mg loading dose followed by 75 mg once daily for 2 weeks
DRUGAspirin
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
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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.) | Day 14 and Day 28, 4 Hrs Post Dose. | 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. | Day 14, and day 28, 4 hours post dose | 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
| Measure | Time frame | Description |
|---|---|---|
| Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 15 | Day 15, 4 hrs post switching | 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 | 4 hrs post first dose 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. |
| Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 15 | Day 15, 4 hrs post switching | 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 | 4 hrs post first dose 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. |
Countries
Canada, Denmark, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Clopidogrel Non-responders - Clopidogrel to Ticagrelor Non-responder definition: patients with an absolute difference of less than or equal to 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist | 20 |
| Clopidogrel Non-responders - Ticagrelor to Clopidogrel Non-responder definition: patients with an absolute difference of less than or equal to 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist | 21 |
| Clopidogrel Responders - Clopidogrel to Clopidogrel Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist | 13 |
| Clopidogrel Responders - Clopidogrel to Ticagrelor Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist | 16 |
| Clopidogrel Responders - Ticagrelor to Clopidogrel Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist | 14 |
| Clopidogrel Responders - Ticagrelor to Ticagrelor Responder definition: patients with an absolute difference greater than 10% between baseline and post-treatment platelet aggregation (maximum extent) with 20 μM ADP used as the agonist | 14 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 0 | 0 | 0 | 1 |
| Overall Study | Developement of discontinuation criteria | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other | 0 | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Severe Non-compliance to protocol | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Clopidogrel Non-responders - Clopidogrel to Ticagrelor | Clopidogrel Non-responders - Ticagrelor to Clopidogrel | Clopidogrel Responders - Clopidogrel to Clopidogrel | Clopidogrel Responders - Clopidogrel to Ticagrelor | Clopidogrel Responders - Ticagrelor to Clopidogrel | Clopidogrel Responders - Ticagrelor to Ticagrelor | Total |
|---|---|---|---|---|---|---|---|
| Age Continuous | 67.25 year STANDARD_DEVIATION 8.12 | 64.57 year STANDARD_DEVIATION 6.31 | 65.46 year STANDARD_DEVIATION 8.68 | 64.56 year STANDARD_DEVIATION 8.56 | 63.21 year STANDARD_DEVIATION 9.23 | 61.57 year STANDARD_DEVIATION 8.22 | 64.8 year STANDARD_DEVIATION 7.95 |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 3 Participants | 2 Participants | 3 Participants | 1 Participants | 22 Participants |
| Sex: Female, Male Male | 15 Participants | 13 Participants | 10 Participants | 14 Participants | 11 Participants | 13 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 39 | 13 / 39 | 1 / 18 | 4 / 18 | 19 / 44 | 14 / 42 | 2 / 13 | 1 / 16 |
| serious Total, serious adverse events | 2 / 39 | 0 / 38 | 0 / 18 | 0 / 18 | 2 / 44 | 0 / 42 | 0 / 13 | 0 / 16 |
Outcome results
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.
Time frame: Day 14, and day 28, 4 hours post dose
Population: Intent-to-treat analysis set: included patients who were assigned to a cohort, randomised to a treatment group, received at least one dose of study drug, and contributed post baseline data. 32 subjects had IPA data; but 1 subject missing a treatment arm, did not qualify for McNemar's test.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-responder: Ticagrelor | 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. | 81.3 Percent of participants |
| Non-responder: Clopidogrel | 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. | 25.0 Percent of participants |
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.
Time frame: Day 14 and Day 28, 4 Hrs Post Dose.
Population: Intent-to-treat analysis set: included patients who were assigned to a cohort, randomised to a treatment group, received at least one dose of study drug, and contributed post baseline data. 32 subjects had IPA data; but 1 subject missing a treatment arm, did not qualify for McNemar's test.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-responder: Ticagrelor | 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.) | 100 Percent of Participants |
| Non-responder: Clopidogrel | 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.) | 93.8 Percent of Participants |
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.
Time frame: Day 15, 4 hrs post switching
Population: Intent-to-treat analysis set: included patients who were assigned to a cohort, randomised to a treatment group, received at least one dose of study drug, and contributed post baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Non-responder: Ticagrelor | Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 15 | 95.0 Percent |
| Non-responder: Clopidogrel | Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 15 | 48.5 Percent |
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.
Time frame: 4 hrs post first dose on day 28
Population: Intent-to-treat analysis set: included patients who were assigned to a cohort, randomised to a treatment group, received at least one dose of study drug, and contributed post baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Non-responder: Ticagrelor | Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 28 | 77.4 Percent |
| Non-responder: Clopidogrel | Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Clopidogrel to Clopidogrel Versus Clopidogrel to Ticagrelor on Day 28 | 60.8 Percent |
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.
Time frame: Day 15, 4 hrs post switching
Population: Intent-to-treat analysis set: included patients who were assigned to a cohort, randomised to a treatment group, received at least one dose of study drug, and contributed post baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Non-responder: Ticagrelor | Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 15 | 66.7 Percent |
| Non-responder: Clopidogrel | Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 15 | 65.3 Percent |
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.
Time frame: 4 hrs post first dose on day 28
Population: Intent-to-treat analysis set: included patients who were assigned to a cohort, randomised to a treatment group, received at least one dose of study drug, and contributed post baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Non-responder: Ticagrelor | Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 28 | 91.0 Percent |
| Non-responder: Clopidogrel | Clopidogrel Responders Final Extent IPA Post Switching Treatment - Comparing Ticagrelor to Ticagrelor Versus Ticagrelor to Clopidogrel on Day 28 | 61.2 Percent |