Ticagrelor Administered as Standard Tablet or Orodispersible Formulation (TASTER)

• ClinicalTrials.gov Identifier: NCT03822377
• Recruitment Status: Completed
• First Posted: January 30, 2019
• Results First Posted: September 8, 2021
• Last Update Posted: September 8, 2021
• Sponsor: Azienda Ospedaliero Universitaria di Sassari
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Prof. Guido Parodi, Azienda Ospedaliero Universitaria di Sassari

Study Description

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.

Condition or disease	Intervention/treatment	Phase
ST Elevation Myocardial Infarction; NSTEMI - Non-ST Segment Elevation MI	Drug: Ticagrelor orodispersible tablets; Drug: Ticagrelor standard tablets	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 130 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.
• Masking: Single (Investigator)
• Masking Description: Site investigators performing platelet function tests will be blinded regarding patient randomization arm and the blood samples will be fully anonymized.
• Primary Purpose: Treatment
• Official Title: Ticagrelor Administered as Standard Tablet or orodispersiblE foRmulation
• Actual Study Start Date: June 27, 2019
• Actual Primary Completion Date: August 31, 2020
• Actual Study Completion Date: August 31, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ticagrelor orodispersible tablets; STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as orodispersible tablets. Intervention: administration of Ticagrelor 180 mg loading dose as orodispersible tablets.	Drug: Ticagrelor orodispersible tablets; Ticagrelor loading dose (180 mg) given as two orodispersible tablets (each of 90 mg), to be dispersed in saliva.
Active Comparator: Ticagrelor standard tablets; STEMI or very high-risk NSTEMI patients undergoing primary PCI and receiving Ticagrelor 180 mg loading dose as standard coated tablets. Intervention: administration of Ticagrelor 180 mg loading dose as standard coated pills.	Drug: Ticagrelor standard tablets; Ticagrelor loading dose (180 mg) given as two standard coated tablets (each of 90 mg) to be swallowed with water.

Outcome Measures

Primary Outcome Measures :

1. Evaluation of Platelet Inhibition [ Time Frame: 1 hour ]

   Platelet reactivity will be measured by VerifyNow test 1 hour after Ticagrelor loading dose (LD) administered as orodispersible tablets as compared with standard formulation in 130 patients with STEMI or very high-risk NSTEMI undergoing immediate PCI.

   The VerifyNow PRU Test is designed to measure P2Y12 receptor blockade. Results of the PRU Tests are reported as P2Y12 Reaction Units (PRU). PRU measures the extent of platelet aggregation in the presence of a P2Y12 inhibitor. Lower PRU levels are associated with expected antiplatelet effect.

Secondary Outcome Measures :

1. Percent of Patients With Insufficient Antiaggregation [ Time Frame: 1 hour ]
   The percent of patients with a high residual platelet reactivity (PRU > 208 by VerifyNow test), thus not adequately antiaggregated, 1 hour after Ticagrelor LD.
2. Number of Participants With Residual Platelet Reactivity at Various Timepoints [ Time Frame: 2, 4 and 6 hours ]
   Residual platelet reactivity (PRU) at 2, 4 and 6 hours measured by VerifyNow test to assess antiplatelet effect of P2Y12 inhibitors
3. Number of Participants With Clinically Relevant Bleeding Events [ Time Frame: 30 days ]
   Actionable bleeding events across the two different regimens of Ticagrelor administration, requiring diagnostic studies, hospitalization, or treatment by a health care professional (BARC type 2 or higher)

Other Outcome Measures:

1. Number of Participants With Morphine-ticagrelor Interaction [ Time Frame: 6 hours ]
   Potential morphine-ticagrelor interaction will be assessed by stratified randomization according to morphine use
2. Incidence of Adverse Events Occurring During Hospital Stay [ Time Frame: Until discharge from the hospital (usually up to 7 days) ]
   Combined ticagrelor administration-related adverse events defined as in-hospital ≥2 BARC bleedings, dyspnea, ventricular pauses, allergic reactions, or vomit

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Italy

Cardiologia Clinica e Interventistica - AOU Sassari

Sassari, Italy, 07100

Sponsors and Collaborators

Azienda Ospedaliero Universitaria di Sassari

AstraZeneca

Investigators

• Principal Investigator: Guido Parodi, Professor; Cardiologia Clinica e Interventistica - AOU Sassari

  Study Documents (Full-Text)

Documents provided by Prof. Guido Parodi, Azienda Ospedaliero Universitaria di Sassari:

Study Protocol and Statistical Analysis Plan  [PDF] January 7, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Prof. Guido Parodi, Professor, Azienda Ospedaliero Universitaria di Sassari
• ClinicalTrials.gov Identifier: NCT03822377
• Other Study ID Numbers: ESR-17-13174; 2018-001790-25 ( EudraCT Number )
• First Posted: January 30, 2019
• Results First Posted: September 8, 2021
• Last Update Posted: September 8, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Myocardial Infarction; ST Elevation Myocardial Infarction; Infarction; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Ticagrelor; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs