Ticagrelor Loading Dose Versus Clopidogrel Loading and Reloading With Ticagrelor.

This study is currently recruiting participants.
Verified November 2013 by University of Patras
Sponsor:
Information provided by (Responsible Party):
Dimitrios Alexopoulos, University of Patras
ClinicalTrials.gov Identifier:
NCT01961856
First received: October 9, 2013
Last updated: November 5, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Platelet Reactivity
Drug: Clopidogrel and Ticagrelor
Drug: Ticagrelor
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
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).

Resource links provided by NLM:


Further study details as provided by University of Patras:

Primary Outcome Measures:
  • Platelet Reactivity between the two groups at 24 hours [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Platelet reactivity between the two groups at 4 hours [ Time Frame: 4 hours ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Platelet reactivity between the two groups at hour 2 [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
  • Percentage of patients presenting high platelet reactivity (HPR) (≥208 PRU) between the two groups at hour 2 [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
  • Percentage of patients presenting high platelet reactivity (HPR) (≥208 PRU) between the two groups at hour 4 [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
  • Percentage of patients presenting high platelet reactivity (HPR) (≥208 PRU) between the two groups at hour 6 [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
  • Percentage of patients presenting high platelet reactivity (HPR) (≥208 PRU) between the two groups at hour 24 [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Overall ST segment deviation in all electrocardiogram leads except aVR between groups at 90 min after first balloon inflation [ Time Frame: 90 min ] [ Designated as safety issue: No ]
  • Overall ST segment deviation in all electrocardiogram leads except aVR between groups at 180 minutes after the first balloon inflation [ Time Frame: 180 minutes ] [ Designated as safety issue: No ]
  • Overall ST segment deviation in all electrocardiogram leads except aVR between groups at discharge [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • Percentage of patients with ≥50% resolution of ST deviation in all leads except aVR (in comparison to hour 0) at 90 minutes after the first balloon inflation, between the two groups. [ Time Frame: 90 minutes ] [ Designated as safety issue: No ]
  • Percentage of patients with ≥50% resolution of ST deviation in all leads except aVR (in comparison to hour 0) at 180 minutes after the first balloon inflation, between the two groups. [ Time Frame: 180 minutes ] [ Designated as safety issue: No ]
  • Percentage of patients with ≥50% resolution of ST deviation in all leads except aVR (in comparison to hour 0)at discharge, between the two groups. [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • Percentage of patients with ≥50% resolution of ST elevation in all leads except aVR (in comparison to hour 0) at 90 minutes after the first balloon inflation, between the two groups. [ Time Frame: 90 minutes ] [ Designated as safety issue: No ]
  • Percentage of patients with ≥50% resolution of ST elevation in all leads except aVR (in comparison to hour 0) at 180 minutes after the first balloon inflation, between the two groups. [ Time Frame: 180 minutes ] [ Designated as safety issue: No ]
  • Percentage of patients with ≥50% resolution of ST elevation in all leads except aVR (in comparison to hour 0) at discharge between the two groups. [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • Overall ST segment elevation in all electrocardiogram leads except aVR between groups at 90 min after first balloon inflation [ Time Frame: 90 minutes ] [ Designated as safety issue: No ]
  • Overall ST segment elevation in all electrocardiogram leads except aVR between groups at 180 min after first balloon inflation [ Time Frame: 180 min ] [ Designated as safety issue: No ]
  • Overall ST segment elevation in all electrocardiogram leads except aVR between groups at discharge [ Time Frame: 5 days ] [ Designated as safety issue: No ]
  • Area under the curve (AUC) defined by Troponin I values assessed at 0 hour, 4, 12, 24, 48 and 72 hours between the two groups. [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Area under the curve (AUC) defined by CK-MB values assessed at 0 hour, 4, 12, 24, 48 and 72 hours between the two groups. [ Time Frame: 72 hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 68
Study Start Date: September 2013
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ticagrelor
Ticagrelor 180mg loading dose
Drug: Ticagrelor
Ticagrelor 180mg loading dose
Experimental: Clopidogrel and Ticagrelor
Clopidogrel 600mg loading dose followed by a Ticagrelor 180mg loading dose 2 hours later
Drug: Clopidogrel and Ticagrelor
Clopidogrel 600mg loading dose followed by Ticagrelor 180mg loading dose

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01961856

Contacts
Contact: Dimitrios Alexopoulos, Professor 00302610999281 dalex@med.upatras.gr

Locations
Greece
Patras University Hospital Recruiting
Patras, Achaia, Greece, 26500
Contact: Dimitrios Alexopoulos, Professor    00302610999281    dalex@med.upatras.gr   
Principal Investigator: Dimitrios Alexopoulos, Professor         
Sponsors and Collaborators
University of Patras
  More Information

No publications provided

Responsible Party: Dimitrios Alexopoulos, Professor, University of Patras
ClinicalTrials.gov Identifier: NCT01961856     History of Changes
Other Study ID Numbers: PATRASCARDIOLOGY-17
Study First Received: October 9, 2013
Last Updated: November 5, 2013
Health Authority: Greece: Ethics Committee

Keywords provided by University of Patras:
platelet reactivity
ticagrelor loading dose
clopidogrel loading dose

Additional relevant MeSH terms:
Myocardial Infarction
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Clopidogrel
Ticlopidine
Ticagrelor
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on April 17, 2014