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This is a single-center, prospective, randomized, single-blind, investigator initiated, pharmacokinetic/pharmacodynamic study of parallel design.Patients with ST elevation myocardial infarction (symptom onset<12 hours), undergoing primary percutaneous coronary intervention, who are P2Y12 inhibitor naïve, will be randomized after informed consent, immediately after diagnostic coronary angiography, in a 1:1 ratio to either:
Preparation of Ticagrelor liquid formulation:
Crushed and dispersed Ticagrelor 180mg for oral administration will be prepared as follows: two ticagrelor 90mg tablets are placed in a mortar and crushed for 60 s using a pestle. 20 mL of purified water will be added in the mortar and stirred for 60s. The liquid is transferred to a dosing cup and another 15 mL of purified water is added to the mortar and stirred, ensuring that all powder has been dispersed and none remained on the mortar and pestle. Again the liquid is transferred to the dosing cup. The same procedure is repeated with 15 ml of purified water.The total contents are stirred for another 30 s to ensure that all remaining tablet particles are dispersed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ticagrelor 180mg whole tablets | Active Comparator | Ticagrelor 180mg loading dose, in the form of 2 whole tablets administered per os in the supine position (standard administration) |
|
| Ticagrelor 180mg crushed and dispersed | Experimental | Ticagrelor 180mg in the form of 2 tablets crushed and dispersed in purified water administered per os with 1-minute-stay in a 60-70 degrees semi-upright sitting position |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ticagrelor 180mg whole tablets | Drug |
| ||
| Ticagrelor 180mg crushed and dispersed |
| Measure | Description | Time Frame |
|---|---|---|
| Ticagrelor's Cmax over 1 hour post ticagrelor administration | 1 hour | |
| Area under the ticagrelor plasma concentration versus time curve (AUC0-1) over 1 hour post ticagrelor administration | 1 hour |
| Measure | Description | Time Frame |
|---|---|---|
| Platelet reactivity at 1 hour post randomization | Platelet reactivity assessment with the VerifyNow assay | 1 hour |
| HPR rate at 1 hour post randomization | HPR rate at 1 hour post randomization between the two treatment arms |
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Inclusion Criteria:
Exclusion Criteria:
Pregnancy/Breastfeeding
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Patras University Hospital Department of Cardiology | Pátrai | Achaia | 26500 | Greece |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26315810 | Derived | Alexopoulos D, Barampoutis N, Gkizas V, Vogiatzi C, Tsigkas G, Koutsogiannis N, Davlouros P, Hahalis G, Nylander S, Parodi G, Xanthopoulou I. Crushed Versus Integral Tablets of Ticagrelor in ST-Segment Elevation Myocardial Infarction Patients: A Randomized Pharmacokinetic/Pharmacodynamic Study. Clin Pharmacokinet. 2016 Mar;55(3):359-67. doi: 10.1007/s40262-015-0320-0. |
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| Drug |
|
| 1 hour |
| Platelet reactivity at 2 hours post randomization | Platelet reactivity assessment with the VerifyNow assay | 2 hours |
| HPR rate at 2 hours post randomization | HPR rate at 2 hours post randomization between the 2 treatment arms. | 2 hours |
| AR-C124910XX Cmax over 1 hour post ticagrelor administration | 1 hour |
| AR-C124910XX Cmax over 6 hours post ticagrelor administration | 6 hours |
| Ticagrelor Cmax over 6 hours post ticagrelor administration | 6 hours |
| Area under the AR-C124910XX plasma concentration versus time curve (AUC0-1) over 1 hour post ticagrelor administration | 1 hour |
| Area under the AR-C124910XX plasma concentration versus time curve (AUC0-6) over 6 hours post ticagrelor administration | 6 hours |
| Area under the Ticagrelor plasma concentration versus time curve (AUC0-6) over 6 hours post ticagrelor administration | 6 hours |
| Time for the maximum plasma concentration (Tmax) of Ticagrelor over 6 hours post Ticagrelor administration | 6 hours |
| Time for the maximum plasma concentration (Tmax) of AR-C124910XX over 6 hours post Ticagrelor administration | 6 hours |
| ID | Term |
|---|---|
| D000072657 | ST Elevation Myocardial Infarction |
| ID | Term |
|---|---|
| D009203 | Myocardial Infarction |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
| D007238 | Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
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| ID | Term |
|---|---|
| D000077486 | Ticagrelor |
| ID | Term |
|---|---|
| D000241 | Adenosine |
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
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