Ticagrelor Loading Dose Versus Clopidogrel Loading and Reloading With Ticagrelor.
Information source: University of Patras
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Platelet Reactivity
Intervention: Clopidogrel and Ticagrelor (Drug); Ticagrelor (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: University of Patras
Summary
In the PLATO substudy referring to patients presenting with an ST-elevation Myocardial
Infarction(STEMI), out of the 4201 who received ticagrelor, 1326 had been pre-treated with a
600mg clopidogrel loading dose (LD) within 24 hours prior to randomization. It is a logical
assumption, that patients who are being reloaded with ticagrelor will demonstrate reduced
platelet reactivity (PR) at 24 hours, in comparison to those who were initially loaded with
ticagrelor, due to the synergistic antiplatelet effect. Single loading with ticagrelor
though, will possibly be accompanied by a smaller bleeding potency compared to reloading
with ticagrelor. Therefore, we assume that single loading with ticagrelor is non-inferior to
reloading with ticagrelor, in terms of platelet reactivity.
P2Y12 inhibitor naive patients with STEMI, they will be randomized immediately after
coronary angiography (Hour 0) in receiving either Ticagrelor 180mg LD or Clopidogrel 600mg
LD and 2 hours later reloading with Ticagrelor 180mg, after written informed consent. PR
will be measured, using the VerifyNow assay at randomization (Hour 0) and at 2, 4, 6 and 24
hours post randomization. In addition, a 12-lead ECG will be performed before randomization,
90 and 180 minutes after the first balloon inflation, as well as on the exit day. Troponin I
and CK-MB will be assessed at randomization and at hour 4, 12, 24, 48 and 72 after
randomization.
Non inferiority of Ticagrelor LD versus Ticagrelor re-LD would be accepted if the upper
bound of the 2-sided 95% CI around the estimated LS mean difference (Ticagrelor LD minus
Ticagrelor re-LD) in the primary end point (PR at 24 hours) would lie bellow Δ=35 PRU. This
non-inferiority margin (Δ) represents the upper bound of the LS mean difference in PR
between Ticagrelor and Prasugrel arm at 24 hours after LD in a pharmacodynamic study of 55
STEMI patients.
Considering previous studies PR at 24 hours post randomization was estimated at 47±40 PRU
and 41±35 PRU for Ticagrelor only LD and Ticagrelor re-LD group respectively. To obtain 85%
statistical power with a 2-sided alpha=0. 05, approximately 32 patients in each treatment
group (64 in total) would be needed to establish the primary hypothesis using the
abovementioned non-inferiority margin of 35 PRU. Anticipating a 5% dropout rate, enrollment
was set to at least 68 patients. The primary endpoint, as well as PR at all the other time
points of the study will be analyzed separately via a mixed effect model with treatment as
fixed effect, patient as a random intercept and PR at baseline as a covariate. Least squares
estimates of the mean difference will be presented, with 95% confidence intervals and a
two-sided p-value for the treatment effect. P values for secondary endpoints will be
reported for two-tailed tests of superiority.
Clinical Details
Official title: Platelet Reactivity After Ticagrelor Loading Dose Versus Clopidogrel Loading Dose and Reloading With Ticagrelor, in Patients With ST-elevation Myocardial Infarction (STEMI) Undergoing Primary Percutaneous Coronary Intervention (PCI).
Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Platelet Reactivity between the two groups at 24 hours
Secondary outcome: Platelet reactivity between the two groups at 4 hours
Eligibility
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Age 18-80 years old
- Patients with STEMI (pain onset <12 hours) undergoing primary PCI
- P2Y12 inhibitor naive
- Written informed consent
Exclusion Criteria:
- Peri-procedural IΙb/IIIa inhibitor administration
- Cardiogenic shock/hemodynamic instability
- Pseudo-aneurism, retroperitoneal hematoma, major bleeding (need for transfusion or Hb
decline≥5 gr/ dl)
- Need for anticoagulant treatment
- Current or future administration of other thienopyridines or ADP receptor inhibitors
- Known thrombocytopenia (<100. 000 / μL) at randomization
- Hct <30% or Hct > 52% during randomization
- Known allergy to clopidogrel or ticagrelor
- Recent (< 6 weeks) major operation, including CABG
- History of bleeding disorders
- Known intracranial mass, arteriovenous shunt or aneurism
- Previous intracranial bleeding
- INR>1,5
- Other clinical conditions associated with increased bleeding risk, according to the
investigators' judgment
- Known creatinine Clearance <30ml/h at randomization or hemodialysis
- Severe/moderate liver failure
- Pregnancy/ breastfeeding
- Increased risk for bradyarrhythmias, according to the investigator's judgment
- Administration of potent CYP3A inhibitor (ketoconazole, itraconazole, voriconazole,
telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir,
indinavir, atazanavir, grapefruit juice N1 L/d), substrates of CYP3A with narrow
therapeutic range (cyclosporine, quinidine), or potent CYP3A inducers (rifampin
/rifampicin, phenytoin, carbamazepine)
- Severe uncontrolled chronic obstructive pulmonary disease
Locations and Contacts
Patras University Hospital, Patras, Achaia 26500, Greece
Additional Information
Starting date: September 2013
Last updated: August 19, 2015
|