Cardiac Arrest, Myocardial Infarction (ST-Elevation Myocardial Infarction and Non-ST-Elevation Myocardial Infarction), Postresuscitation Syndrome
Conditions
Keywords
Antiplatelet Therapy, Cardiac Arrest, Therapeutic hypothermia, Myocardial infarction (ST-Elevation Myocardial Infarction and Non-ST-Elevation Myocardial Infarction)
Brief summary
There is growing evidence that standard dual antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel is not as effective in the setting of therapeutic hypothermia after cardiac arrest as in normothermic patients. The reasons for this are probably slower gastrointestinal motility, absorption and liver metabolism required for clopidogrel to take action. Since ticagrelor has faster intestinal absorption and no need for liver metabolism we expect its effect to be good even in patients with therapeutic hypothermia after cardiac arrest. Patients treated with therapeutic hypothermia after cardiac arrest and percutaneous coronary intervention will be randomised into two groups. One will be treated with ASA and clopidogrel and the other with ASA and ticagrelor. Blood samples will be collected before and 2, 4, 12, 22 and 48 hours after P2Y12 inhibitor administration. Platelet function will be measured by VerifyNow P2Y12 assay and by Multiplate ADPTest. Differences between the groups will be analysed. Hypothesis: Antiplatelet therapy with ticagrelor is more effective than therapy with clopidogrel in the comatose survivors of cardiac arrest treated with therapeutic hypothermia and percutaneous coronary intervention (PCI).
Interventions
DRUGClopidogrel
DRUGTicagrelor
Sponsors
University Medical Centre Ljubljana
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female and male over 18 years old * Unconscious survivors of cardiac arrest treated with therapeutic hypothermia * Acute coronary syndrome (NSTEMI or STEMI) as a reason of cardiac arrest * PCI with stent implantation * Provision of informed consent prior to any study specific procedures is impossible because subjects are unconscious at the moment of inclusion
Exclusion criteria
* Use of any P2Y12 inhibitors in last 10 days * Use of prasugrel before and 48 hours after loading dose of P2Y12 inhibitor * Use of eptifibatide before and 48 hours after loading dose of P2Y12 inhibitor * Thrombocytopenia (\<50\*109/L) * Allergic reaction to acetylsalicylic acid, clopidogrel or ticagrelor * Ticagrelor contraindications: previous intracranial bleeding, active pathological bleeding, moderate to severe hepatic impairment, heart rate \< 40/min at presentation * Suspected or confirmed pregnancy * Use of bivalirudin before and 48 hours after loading dose of P2Y12 inhibitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| VerifyNow P2Y12Test - Platelet Reactivity | 12 h after P2Y12 inhibitor loading | Platelet reactivity reflects P2Y12 inhibitor effect. Higher values mean normal platelet reactivity due to low P2Y12 inhibition response, while lower values mean decreased platelet reactivity due to the effect of a P2Y12 inhibitor. High on-treatment platelet reactivity was defined as \>208 PRU. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| VerifyNow P2Y12Test - % Inhibition | 12 hours after P2Y12 inhibitor loading | % inhibition reflects P2Y12 inhibitor effect regarding basal platelet reactivity (defined as: (1- (platelet reactivity/basal platelet reactivity)) x 100). Higher values mean better P2Y12 inhibition response. High on-treatment platelet reactivity was defined as \<11% inhibition. |
| Multiplate ADP Test | 12 hours after P2Y12 inhibitor loading | Platelet activation by adenosine diphosphate (ADP) expressed in arbitrary aggregation units (U). P2Y12 inhibitors block ADP receptors and decrease platelet activation by ADP. Higher values mean less effect of P2Y12 inhibitors, lower values mean more effect of P2Y12 inhibitors on platelets. High on-treatment platelet reactivity was defined as \>46 U. |
Countries
Slovenia
Participant flow
Recruitment details
Recruitment from August 2014 to May 2016 at UMC Ljubljana, Slovenia, Europe
Pre-assignment details
Reasons for exclusion were intraprocedural eptifibatide/thrombolysis (11), decision of attending physician (8) and bradycardia (1)
Participants by arm
| Arm | Count |
|---|---|
| Clopidogrel These patients were treated with clopidogrel 600 mg loading and than 75 mg/24 h. | 16 |
| Ticagrelor These patients were treated with ticagrelor 180 mg loading and than 90 mg/12 h. | 20 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
Baseline characteristics
| Characteristic | Clopidogrel | Ticagrelor | Total |
|---|---|---|---|
| Age, Continuous | 64 years STANDARD_DEVIATION 9 | 61 years STANDARD_DEVIATION 12 | 62 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 13 Participants | 17 Participants | 30 Participants |
| ST-Elevation Myocardial Infarction in postresuscitation ECG | 12 Participants | 16 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 16 | 9 / 20 |
| other Total, other adverse events | 10 / 16 | 10 / 20 |
| serious Total, serious adverse events | 7 / 16 | 9 / 20 |
Outcome results
Primary
VerifyNow P2Y12Test - Platelet Reactivity
Platelet reactivity reflects P2Y12 inhibitor effect. Higher values mean normal platelet reactivity due to low P2Y12 inhibition response, while lower values mean decreased platelet reactivity due to the effect of a P2Y12 inhibitor. High on-treatment platelet reactivity was defined as \>208 PRU.
Time frame: 12 h after P2Y12 inhibitor loading
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clopidogrel | VerifyNow P2Y12Test - Platelet Reactivity | 238 PRU | Standard Deviation 67 |
| Ticagrelor | VerifyNow P2Y12Test - Platelet Reactivity | 101 PRU | Standard Deviation 75 |
Secondary
Multiplate ADP Test
Platelet activation by adenosine diphosphate (ADP) expressed in arbitrary aggregation units (U). P2Y12 inhibitors block ADP receptors and decrease platelet activation by ADP. Higher values mean less effect of P2Y12 inhibitors, lower values mean more effect of P2Y12 inhibitors on platelets. High on-treatment platelet reactivity was defined as \>46 U.
Time frame: 12 hours after P2Y12 inhibitor loading
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clopidogrel | Multiplate ADP Test | 28 U | Standard Deviation 17 |
| Ticagrelor | Multiplate ADP Test | 15 U | Standard Deviation 10 |
Secondary
VerifyNow P2Y12Test - % Inhibition
% inhibition reflects P2Y12 inhibitor effect regarding basal platelet reactivity (defined as: (1- (platelet reactivity/basal platelet reactivity)) x 100). Higher values mean better P2Y12 inhibition response. High on-treatment platelet reactivity was defined as \<11% inhibition.
Time frame: 12 hours after P2Y12 inhibitor loading
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clopidogrel | VerifyNow P2Y12Test - % Inhibition | 4 % inhibition | Standard Deviation 11 |
| Ticagrelor | VerifyNow P2Y12Test - % Inhibition | 55 % inhibition | Standard Deviation 32 |