Non-ST Elevation Acute Coronary Syndrome
Conditions
Keywords
Percutaneous Coronary Intervention
Brief summary
The purpose of this study is to determine if ticagrelor is as effective as clopidogrel in rate of onset and degree of platelet inhibition for patients with non-ST elevation of acute coronary syndrome (NSTE-ACS) undergoing ad hoc percutaneous coronary intervention (PCI) with bivalirudin.
Detailed description
Multi-center, open-label study that will compare the onset of the platelet inhibition with ticagrelor versus clopidogrel when administered with bivalirudin during PCI on a background therapy of aspirin in patients with NSTE-ACS.
Interventions
DRUGticagrelor
Single loading dose of 180mg of ticagrelor at time of bivalirudin administration. Beginning 12 hrs following study drug administration, all pts in the ticagrelor arm will receive ticagrelor 90 mg (maintenance dose) approximately every 12 hrs until Follow-up telephone contact.
DRUGclopidogrel
Single loading oral dose of 600 mg of clopidogrel will be given at time of bivalirudin administration. Beginning 4 hrs following study drug administration, all pts in the clopidorgrel arm will receive ticagrelor 180 mg for the loading dose, followed by 90 mg maintenance dose approximately every 12 hours until the Follow-up telephone contact.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Hospitalised for chest pain and potential acute coronary syndrome. * Onset of the most recent cardiac ischemic symptoms must occur within 7 days before randomisation and documented by cardiac ischemic symptoms of ≥ 10 min duration at rest and at least 2 of the following: ST segment changes on electrocardiogram (ECG) indicative of ischemia, or Positive biomarker evdience of myocardial necrosis, or other risk factors such as: 60 yrs of age or older, previous myocardial infarction or coronary bypass surgery, multi-vessel coronary artery disease, diabetes mellitus, peripheral arterial disease, chronic renal disfunction. * Females must be either surgically sterile or post-menopausal. * Activated Clotting Time (ACT) \</= 300 at the time of study treatment
Exclusion criteria
* Participation in another clinical study with an investigational product during the last 30 days. * Current acute complication of percutaneous coronary intervention or coronary bypass surgery. * Any contraindication to ticagrelor, clopidogrel or bivalirudin. * ST elevation myocardial infraction within 24 hours of study entry. * Any indications for oral anticoagulation or aspirin dose other than 75 to 100 milligrams (mg) daily. * Planned use of omeprazole or esomeprazole. * Patients with known bleeding or coagulation disorders; patients requiring dialysis; patients who have an inability to swallow medication. * Patients with known bleeding diathesis or coagulation disorder; history of intracranial bleed. * Use of Intravenous (IV) heparin less than 2 hours before procedure. * Sustained uncontrolled high blood pressure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| P2Y12 Reaction Units (PRU) Using VerifyNow™ at 0.5 Hours After Loading Dose | 0.5 hours post loading dose | PRU at 0.5 hours after a single oral loading dose of either ticagrelor 180 mg or clopidogrel 600 mg given at the time of the bivalirudin bolus |
| P2Y12 Reaction Units (PRU) Using VerifyNow™ at 1 Hour After Loading Dose | 1 hour post loading dose | PRU at 1 hour after a single oral loading dose of either ticagrelor 180 mg or clopidogrel 600 mg given at the time of the bivalirudin bolus |
Countries
United States
Participant flow
Recruitment details
This study was conducted in the USA. While 17 sites were activated, 9 sites enrolled patients, and only 7 sites successfully randomised patients. There were 34 patients screened, 21 screen failures and 13 randomised patients from 03 September 2014 and 20 April 2015. The study was terminated due to recruitment challenges and low enrolment concerns.
Participants by arm
| Arm | Count |
|---|---|
| Ticagrelor A single oral dose of 180 mg (90 mg tablet x2) of ticagrelor was administered at the time of the initial bivalirudin bolus administration. | 7 |
| Clopidogrel A single oral dose of 600 mg (300 mg tablet x2) of clopidogrel was administered at the time of the initial bivalirudin bolus administration. | 6 |
| Total | 13 |
Baseline characteristics
| Characteristic | Ticagrelor | Clopidogrel | Total |
|---|---|---|---|
| Age, Continuous | 63.9 Years STANDARD_DEVIATION 2.7 | 61.2 Years STANDARD_DEVIATION 14.7 | 62.6 Years STANDARD_DEVIATION 9.8 |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 7 | 2 / 6 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 |
Outcome results
Primary
P2Y12 Reaction Units (PRU) Using VerifyNow™ at 0.5 Hours After Loading Dose
PRU at 0.5 hours after a single oral loading dose of either ticagrelor 180 mg or clopidogrel 600 mg given at the time of the bivalirudin bolus
Time frame: 0.5 hours post loading dose
Population: 10 patients were included in the pharmacodynamic (PD) analysis: 6 patients in the ticagrelor group and 4 patients in the clopidogrel group. 3 out 13 randomized pateints are excluded (1 patient without any PRU data, 2 pateints with protocol deviations)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor | P2Y12 Reaction Units (PRU) Using VerifyNow™ at 0.5 Hours After Loading Dose | 289.2 PRUs | Standard Deviation 44.6 |
| Clopidogrel | P2Y12 Reaction Units (PRU) Using VerifyNow™ at 0.5 Hours After Loading Dose | 292.8 PRUs | Standard Deviation 38.7 |
Primary
P2Y12 Reaction Units (PRU) Using VerifyNow™ at 1 Hour After Loading Dose
PRU at 1 hour after a single oral loading dose of either ticagrelor 180 mg or clopidogrel 600 mg given at the time of the bivalirudin bolus
Time frame: 1 hour post loading dose
Population: 10 patients were included in the PD analysis: 6 patients in the ticagrelor group and 4 patients in the clopidogrel group. Out of the 10 patients in the PD analysis, 1 patient in Ticagrelor group does not have PRU value at 1 hour post loading dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ticagrelor | P2Y12 Reaction Units (PRU) Using VerifyNow™ at 1 Hour After Loading Dose | 174.4 PRUs | Standard Deviation 88.9 |
| Clopidogrel | P2Y12 Reaction Units (PRU) Using VerifyNow™ at 1 Hour After Loading Dose | 249.8 PRUs | Standard Deviation 68.7 |