Non ST Segment Elevation Acute Coronary Syndrome
Conditions
Keywords
ticagrelor, loading dose, non-ST-segment elevation acute coronary syndromes, percutaneous coronary intervention, the antiplatelet effects, bleeding events, major adverse cardiac events
Brief summary
It is designed to test the hypothesis that high loading dose(360mg) ticagrelor versus conventional loading dose(180mg) will result in a higher inhibition of platelet aggregation(IPA) without increasing the bleeding events.
Detailed description
After providing written informed consent, all patients will be randomized to receive ticagrelor 360mg or 180mg loading dose(LD),then 90mg bid maintenance dose starting 12 hours after LD.PCI will performed in 2h-72h after they are given the loading dose.All patients should receive acetylsalicylic acid (ASA) 75 to 100 mg daily unless intolerant.IPA at 0, 0.5, 1, 2, 8, 24h after the loading dose of ticagrelor will be measured. CK-MB, troponin I, myoglobin, CRP will be detected at 0h, before PCI, 8h after PCI, 24h after PCI. ECG will be conducted at 0h and within 24h after PCI. Patients returned 28 days for follow-up visits after the loading dose of ticagrelor, documented any adverse events.
Interventions
DRUGticagrelor
Patients will receive ticagrelor 360mg loading dose or 180mg loading dose , then 90mg bid maintenance dose starting 12 hours after loading dose.
Sponsors
General Hospital of Chinese Armed Police Forces
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Provision of informed consent prior to any study specific procedures. * Male or non-pregnant female; aged from 18 to 80 years old. * Patients with non-ST-segment elevation acute coronary syndromes who were scheduled to undergoing PCI.
Exclusion criteria
* Any contraindication against the use of ticagrelor. * On treatment with a P2Y12 receptor antagonist in past 30 days. * Known allergies to aspirin or ticagrelor. * On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban). * Known blood dyscrasia or bleeding diathesis. * ST-segment elevation acute myocardial infarction. * Non-ST segment elevation acute coronary syndrome with high-risk features warranting emergency coronary angiography. * Left ventricular ejection fraction ≤30%; renal failure with creatinine 3 mg/dl; history of liver disease; an increased risk of bradycardia, and concomitant therapy with drugs interfering with CYP3A4 metabolism.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Platelet Reactivity Index(PRI) Measured by VASP-P | 2 hours after the loading dose of ticagrelor | Vasodilator-stimulated phosphoprotein(VASP) phosphorylation, a measure of P2Y12 receptor reactivity, was determined by flow cytometry with the use of the Platelet VASP-FCM Kit (Stago, France)and recorded as the platelet reactivity index (PRI). |
Secondary
| Measure | Time frame |
|---|---|
| Platelet Reactivity Index (PRI) Measured by VASP-P | 0.5hour,1hour,8hours,24hours after the loading dose of ticagrelor |
| Bleeding Events | follow-up for 28 days after the loading dose of ticagrelor |
Countries
China
Participant flow
Recruitment details
A total of 278 patients were recruited at 8 centers in Beijing and allocated into two groups using block randomization: a high LD group (360 mg) and a conventional LD group (180 mg).
Pre-assignment details
Patients excluded(n=564)
Participants by arm
| Arm | Count |
|---|---|
| High Loading Dose of Ticagrelor Patients will receive ticagrelor 360mg loading dose, then 90mg bid maintenance dose starting 12 hours after loading dose.
ticagrelor: Patients will receive ticagrelor 360mg loading dose or 180mg loading dose , then 90mg bid maintenance dose starting 12 hours after loading dose. | 129 |
| Conventional Loading Dose of Ticagrelor Patients will receive ticagrelor 180mg loading dose, then 90mg bid maintenance dose starting 12 hours after loading dose.
ticagrelor: Patients will receive ticagrelor 360mg loading dose or 180mg loading dose , then 90mg bid maintenance dose starting 12 hours after loading dose. | 133 |
| Total | 262 |
Baseline characteristics
| Characteristic | Conventional Loading Dose of Ticagrelor | High Loading Dose of Ticagrelor | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 53 Participants | 54 Participants | 107 Participants |
| Age, Categorical Between 18 and 65 years | 80 Participants | 75 Participants | 155 Participants |
| Age, Continuous | 58.8 years STANDARD_DEVIATION 10.26 | 59.7 years STANDARD_DEVIATION 9.47 | 59.2 years STANDARD_DEVIATION 9.46 |
| Region of Enrollment China | 133 participants | 129 participants | 262 participants |
| Sex: Female, Male Female | 45 Participants | 40 Participants | 85 Participants |
| Sex: Female, Male Male | 88 Participants | 89 Participants | 177 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 139 | 19 / 139 |
| serious Total, serious adverse events | 3 / 139 | 5 / 139 |
Outcome results
Primary
Platelet Reactivity Index(PRI) Measured by VASP-P
Vasodilator-stimulated phosphoprotein(VASP) phosphorylation, a measure of P2Y12 receptor reactivity, was determined by flow cytometry with the use of the Platelet VASP-FCM Kit (Stago, France)and recorded as the platelet reactivity index (PRI).
Time frame: 2 hours after the loading dose of ticagrelor
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Conventional Loading Dose of Ticagrelor | Platelet Reactivity Index(PRI) Measured by VASP-P | 16.7 percentage of 100 |
| High Loading Dose of Ticagrelor | Platelet Reactivity Index(PRI) Measured by VASP-P | 12.2 percentage of 100 |
Secondary
Bleeding Events
Time frame: follow-up for 28 days after the loading dose of ticagrelor
Secondary
Platelet Reactivity Index (PRI) Measured by VASP-P
Time frame: 0.5hour,1hour,8hours,24hours after the loading dose of ticagrelor