Comparing Ticagrelor and Clopidogrel Pharmacodynamics After Thrombolysis
| Status: | Withdrawn |
|---|---|
| Conditions: | Cardiology, Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 4/17/2018 |
| Start Date: | January 2, 2014 |
| End Date: | March 2018 |
A Randomized, Open Label, Pilot Study to Assess the Pharmacodynamics Using Vefiynow and VASP Assay; and Pharmacokinetics of Ticagrelor vs Clopidogrel in Patients Undergoing PCI With History of Fibrinolysis in 24-48 Hours
This study involves doing platelet function testing in patients who have undergone
fibrinolysis. Fibrinolysis (Use of clot busting medicine in heart attack) is the standard of
care to restore blood flow in blocked arteries as soon as possible after the "Heart attack"
in rural health center where access to cardiac catheterization is one hour away. Fibrinolysis
is done by the emergency room physician in a timely fashion to minimize the damage of the
myocardium. Additionally anti-platelet regimen as adjuvant for patient undergoing
fibrinolysis has been well studied in many trials. In this study investigators will use
clopidogrel or ticagrelor in randomized fashion to evaluate anti- platelet effect by
measuring efficacy in vivo (pharmacodynamics) and blood levels of both drugs
(Pharmacokinetics).
fibrinolysis. Fibrinolysis (Use of clot busting medicine in heart attack) is the standard of
care to restore blood flow in blocked arteries as soon as possible after the "Heart attack"
in rural health center where access to cardiac catheterization is one hour away. Fibrinolysis
is done by the emergency room physician in a timely fashion to minimize the damage of the
myocardium. Additionally anti-platelet regimen as adjuvant for patient undergoing
fibrinolysis has been well studied in many trials. In this study investigators will use
clopidogrel or ticagrelor in randomized fashion to evaluate anti- platelet effect by
measuring efficacy in vivo (pharmacodynamics) and blood levels of both drugs
(Pharmacokinetics).
This is an open label randomized pharmacodynamics study to compare platelet function
reactivity of ticagrelor and clopidogrel after PCI in sub-set of patients who have undergone
fibrinolysis at least 24 hour prior to PCI..A total of 70 patients will be enrolled. Prior to
enrollment, patients have already undergone fibrinolysis (selected by the treating
physician), aspirin (recommended dose 324 mg) on the first day and 81 mg daily thereafter,
and Lovenox or heparin as per protocol of referring ER. Patients will undergo coronary
angiography as standard of care and coronary stenting if indicated. Prior to angiography
patient will be enrolled in this open label randomized protocol to receive clopidogrel or
ticagrelor. Patients will be randomly assigned in a 1:1 ratio by open label study to receive
either clopidogrel (Plavix, Sanofi-Aventis and Bristol-Myers Squibb; a 300-mg loading dose
followed by 75 mg once daily) or ticagrelor (Brilinta, AstraZeneca; 180 mg loading and 90 mg
twice daily) by a computerized system of randomization. Patients will receive clopidogrel or
ticagrelor daily from enrollment to discharge. For patients who did not undergo PCI after
enrollment, study drugs will be administered up to and including day 8th or hospital
discharge, whichever comes first. Patients will be treated as per standard of care, and
pharmacodynamics and pharmacokinetic study will be carried as per protocol. VerifyNow and
VASP assay will be used to measure platelet reactivity for pharmacodynamic evaluation of
ticagrelor vs Clopidogrel at specific time points: baseline (time 0), 30 mins, 1 hour, 2
hours, 8 hours and at 24 hours from first oral anti-platelet dose.. Blood will be collected
from the sheath or ante-cubital vein into Vacutainer tubes for platelet function assay as
below by VerifyNow and VASP. VerifyNow P2Y12 Assay: VerifyNow is a turbidimetric based system
that measures platelet aggregation in the whole blood.8 This instrument measures an optical
signal reported as P2Y12 Reaction Units (PRU). Vasodilator-Stimulated Phosphoprotein
Phosphrylation (VASP) Assay: The measure of Vasodilator-Stimulated Phosphoprotein
Phosphrylation (Biocytex Inc. Marseille, France), a method to quantify P2Y12 receptor
reactivity, which reflects the extent of blockade of P2Y12 receptor blockade.9 Platelet
reactivity index (PRI) is calculated by measuring VASP-P levels by mean fluorescence
intensity (MFI) by stimulation with prostaglandin; PGE1and PGE1 plus ADP.
PRI(%)=[(MFIPGE1)−(MFIPGE1+ADP)/(MFIPGE1)]×100%. ) Pharmacokinetic will be done at 30 min, 60
min, 120 min, 4 hours, 8 hours and at 24 hours. AUC from time 0-2 hours, Cmax at 2 hours, and
Tmax at 2 hours for key secondary endpoint. Will collect Cmax and Tmax at all time points to
be consistent, i.e. at 0, 30 min, 1 hour, 2 hour, 8 hours, and 24 hours when you draw PD
measures at those time points and sample will be shipped.
reactivity of ticagrelor and clopidogrel after PCI in sub-set of patients who have undergone
fibrinolysis at least 24 hour prior to PCI..A total of 70 patients will be enrolled. Prior to
enrollment, patients have already undergone fibrinolysis (selected by the treating
physician), aspirin (recommended dose 324 mg) on the first day and 81 mg daily thereafter,
and Lovenox or heparin as per protocol of referring ER. Patients will undergo coronary
angiography as standard of care and coronary stenting if indicated. Prior to angiography
patient will be enrolled in this open label randomized protocol to receive clopidogrel or
ticagrelor. Patients will be randomly assigned in a 1:1 ratio by open label study to receive
either clopidogrel (Plavix, Sanofi-Aventis and Bristol-Myers Squibb; a 300-mg loading dose
followed by 75 mg once daily) or ticagrelor (Brilinta, AstraZeneca; 180 mg loading and 90 mg
twice daily) by a computerized system of randomization. Patients will receive clopidogrel or
ticagrelor daily from enrollment to discharge. For patients who did not undergo PCI after
enrollment, study drugs will be administered up to and including day 8th or hospital
discharge, whichever comes first. Patients will be treated as per standard of care, and
pharmacodynamics and pharmacokinetic study will be carried as per protocol. VerifyNow and
VASP assay will be used to measure platelet reactivity for pharmacodynamic evaluation of
ticagrelor vs Clopidogrel at specific time points: baseline (time 0), 30 mins, 1 hour, 2
hours, 8 hours and at 24 hours from first oral anti-platelet dose.. Blood will be collected
from the sheath or ante-cubital vein into Vacutainer tubes for platelet function assay as
below by VerifyNow and VASP. VerifyNow P2Y12 Assay: VerifyNow is a turbidimetric based system
that measures platelet aggregation in the whole blood.8 This instrument measures an optical
signal reported as P2Y12 Reaction Units (PRU). Vasodilator-Stimulated Phosphoprotein
Phosphrylation (VASP) Assay: The measure of Vasodilator-Stimulated Phosphoprotein
Phosphrylation (Biocytex Inc. Marseille, France), a method to quantify P2Y12 receptor
reactivity, which reflects the extent of blockade of P2Y12 receptor blockade.9 Platelet
reactivity index (PRI) is calculated by measuring VASP-P levels by mean fluorescence
intensity (MFI) by stimulation with prostaglandin; PGE1and PGE1 plus ADP.
PRI(%)=[(MFIPGE1)−(MFIPGE1+ADP)/(MFIPGE1)]×100%. ) Pharmacokinetic will be done at 30 min, 60
min, 120 min, 4 hours, 8 hours and at 24 hours. AUC from time 0-2 hours, Cmax at 2 hours, and
Tmax at 2 hours for key secondary endpoint. Will collect Cmax and Tmax at all time points to
be consistent, i.e. at 0, 30 min, 1 hour, 2 hour, 8 hours, and 24 hours when you draw PD
measures at those time points and sample will be shipped.
Inclusion Criteria:
1. Men and women 18 to 75 years of age
2. Ischemic discomfort lasting more than 20 mins at rest within 12 hours before
randomization
3. ST-segment elevation of at least 0.1 mV in at least two contiguous limb leads,
ST-segment elevation of at least 0.2 mV in at least two contiguous precordial leads,
or left bundle-branch block that was not known to be old
4. Received fibrinolytic agent, an anticoagulant (if a fibrin-specific lytic agent was
prescribed) and aspirin within 24-48 hours
Exclusion Criteria:
1. Hypersensitivity to ticagrelor or clopidogrel
2. Active Pathological Bleeding or history of intracranial bleeding
3. Concomitant use of oral anticoagulant
4. Concomitant use of 40 mg of Simvastatin or lovastatin
5. Concomitant strong CYP3A inhibitors such as ketoconazole, clarithromycin, nefazadone,
ritonavir, atazanavir
6. Concomitant use of CYP2C19 inhibitors such as omeprazole or esomeprazole
7. Patients planned to urgent CABG
8. Thrombocytopenia
9. Dialysis
10. Use of oral antiplatelet agent (ticagrelor, prasugrel, Clopidogrel) within 7 days
prior to enrollment
11. Use of GP IIb/IIIa inhibitors
12. Rescue PCI (PCI < 24 hours from symptom onset) -
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