Clinical trial NCT03822377: Ticagrelor Administered as Standard Tablet or Orodispersible Formulation
Official title: Ticagrelor Administered as Standard Tablet or orodispersiblE foRmulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ST Elevation Myocardial Infarction
NSTEMI - Non-ST Segment Elevation MI
Lead sponsor: Azienda Ospedaliero Universitaria di Sassari
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2019-01-30
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Comparison of platelet inhibition at different timepoints between 65 patients in the treatment arm (receiving orodispersible formulation of ticagrelor loading dose) versus 65 patients in the control arm (receiving standard coated formulation of ticagrelor loading dose). Randomization will be further stratified according to morphine use.
Primary purpose: TREATMENT

Brief summary: Randomized clinical study evaluating superiority in platelet inhibition after administration of Ticagrelor 180 mg loading dose as an orodispersible formulation versus traditional coated tablets in patients admitted for ST elevation myocardial infarction or very high-risk non-ST elevation myocardial infarction.

Detailed description: Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy for patients with acute ST-segment elevation myocardial infarction (STEMI). Additional antithrombotic therapy prior or during intervention plays an important role in the short- and long-term outcomes after PPCI. Oral antiplatelet therapy including a platelet P2Y12 receptor inhibitors is a cornerstone of antithrombotic treatment in patients with acute coronary syndromes. Prasugrel and Ticagrelor have been shown to be superior to Clopidogrel in patients with STEMI in reduction of ischemic complication without any increase in the bleeding risk and with a significant reduction in the stent thrombosis rate. Nevertheless, in STEMI patients, pharmacodynamic studies showed prasugrel and ticagrelor oral loading dose (LD) provided a suboptimal platelet inhibition in the first hours after LD, and at least 4 hours are required to achieve and effective platelet aggregation inhibition in the majority of patients, in part due to slowed gut motility caused by morphine use. Orodispersible tablet (ODT) is a different tablet formulation that disperses upon contact with the moist mucosal surfaces of the oral cavity and quickly release its components before swallowing; thus local drug dissolution and absorption as well as onset of clinical effect can be obtained conveniently easily and quickly by bypassing gastrointestinal tract. Recently, Ticagrelor 90 mg ODT has become available and bioequivalence studies on healthy volunteers documented its effectiveness with consequent approval by European Medicine Agency of this formulation which is currently available on the market. Thus, the aim of the present study is to evaluate the superiority in platelet inhibition with 180 mg Ticagrelor loading dose (LD) administered as ODTs as compared with standard formulation, among patients with STEMI or very high-risk NSTEMI undergoing immediate PCI. Primary objective consists in evaluating platelet reactivity 1 hour after Ticagrelor loading dose by VerifyNow test.

Eligibility criteria: Inclusion Criteria:

1. Patients presenting within 12 hours from the onset of symptoms with STEMI or very high-risk NSTEMI referred for immediate (\< 2 hours) angiography. Very high-risk NSTEMI patients include patients with haemodynamic instability or cardiogenic shock, heart failure, life-threatening arrhythmias or resuscitated cardiac arrest, intermittent ST-segment elevation, or ongoing chest pain.
2. Informed, written consent
3. Male or female patients, aged ≥ 18 years old

Exclusion Criteria:

1. Age \< 18 years
2. Active bleeding; bleeding diathesis; coagulopathy
3. History of gastrointestinal or genitourinary bleeding \<2 months
4. Major surgery in the last 6 weeks
5. History of intracranial bleeding or structural abnormalities
6. Suspected aortic dissection
7. Administration in the week before the index event of clopidogrel, ticlopidine, prasugrel, ticagrelor, thrombolytics, bivalirudin, low-molecular weight heparin or fondaparinux.
8. Concomitant oral or IV therapy with strong CYP3A inhibitors or strong CYP3A inducers, CYP3A with narrow therapeutic window
9. Known relevant hematological deviations: Hb \<10 g/dl, Thromb. \<100x10\^9/l
10. Use of warfarin or new oral anticoagulant derivatives within the last 7 days
11. Known severe liver disease, severe renal failure
12. Allergy or hypersensitivity to ticagrelor or any of the excipients.
13. Pregnancy or lactation

Primary outcomes:
measure: Evaluation of Platelet Inhibition
timeFrame: 1 hour
Secondary outcomes:
measure: Percent of Patients With Insufficient Antiaggregation
timeFrame: 1 hour
measure: Number of Participants With Residual Platelet Reactivity at Various Timepoints
timeFrame: 2, 4 and 6 hours
measure: Number of Participants With Clinically Relevant Bleeding Events
timeFrame: 30 days
Other outcomes:
measure: Number of Participants With Morphine-ticagrelor Interaction
timeFrame: 6 hours
measure: Incidence of Adverse Events Occurring During Hospital Stay
timeFrame: Until discharge from the hospital (usually up to 7 days)
Locations:
city: Sassari
country: Italy
facility: Cardiologia Clinica e Interventistica - AOU Sassari
Study officials:
affiliation: Cardiologia Clinica e Interventistica - AOU Sassari
name: Guido Parodi, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Parodi G, Talanas G, Mura E, Canonico ME, Siciliano R, Guarino S, Marini A, Dossi F, Franca P, Raccis M, Saba PS, Sanna GD. Orodispersible Ticagrelor in Acute Coronary Syndromes: The TASTER Study. J Am Coll Cardiol. 2021 Jul 20;78(3):292-294. doi: 10.1016/j.jacc.2021.05.015. No abstract available.