Standard (180mg) Versus Double (360mg) Loading Dose of Ticagrelor in Patients With ST-elevation Myocardial Infarction (STEMI), Undergoing Primary Percutaneous Coronary Intervention (PCI)

• ClinicalTrials.gov Identifier: NCT01575795
• Recruitment Status: Completed
• First Posted: April 11, 2012
• Last Update Posted: April 10, 2013
• Sponsor: University of Patras
• Information provided by (Responsible Party): Dimitrios Alexopoulos, University of Patras

Tracking Information

• First Submitted Date: April 9, 2012
• First Posted Date: April 11, 2012
• Last Update Posted Date: April 10, 2013
• Study Start Date: April 2012
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 10, 2012)

platelet reactivity at 1 hour post randomization in Group A, between the 2 treatment arms. [ Time Frame: 1 hour ]

platelet reactivity at 1 hour post randomization in Group A, between the 2 treatment arms.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 10, 2012)

• 1. Platelet reactivity at 1 hour post randomization in Group B, between the 2 treatment arms. [ Time Frame: 1 hour ]
  1. Platelet reactivity at 1 hour post randomization in Group B, between the 2 treatment arms.
• 2. Platelet reactivity at 0.5 hour post randomization between the 2 treatment arms separately for Group A and B [ Time Frame: 0.5 hour ]
  Platelet reactivity at 0.5 hour post randomization between the 2 treatment arms separately for Group A and B
• Platelet reactivity at 2 hours post randomization between the 2 treatment arms separately for Group A and B [ Time Frame: 2 hours ]
  Platelet reactivity at 2 hours post randomization between the 2 treatment arms separately for Group A and B
• Platelet reactivity at 4 hours post randomization between the 2 treatment arms separately for Group A and B [ Time Frame: 4 hours ]
  Platelet reactivity at 4 hours post randomization between the 2 treatment arms separately for Group A and B
• 3. High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 0.5 hour post randomization between the 2 treatment arms, separately for Group A and B [ Time Frame: 0.5 hour ]
  High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 0.5 hour post randomization between the 2 treatment arms, separately for Group A and B
• High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 1 hour post randomization between the 2 treatment arms, separately for Group A and B [ Time Frame: 1 hour ]
  High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 1 hour post randomization between the 2 treatment arms, separately for Group A and B
• High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 2 hours post randomization between the 2 treatment arms, separately for Group A and B [ Time Frame: 2 hours ]
  High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 2 hours post randomization between the 2 treatment arms, separately for Group A and B
• High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 4 hours post randomization between the 2 treatment arms, separately for Group A and B [ Time Frame: 4 hours ]
  High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 4 hours post randomization between the 2 treatment arms, separately for Group A and B
• Occurrence of any 5-day bleeding event (BARC Types 1-5) [ Time Frame: 5 days ]
  Occurrence of any 5-day bleeding event (BARC Types 1-5)
• Occurrence of 5-day MACEs [ Time Frame: 5 days ]
  Occurrence of 5-day MACEs

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Standard (180mg) Versus Double (360mg) Loading Dose of Ticagrelor in Patients With ST-elevation Myocardial Infarction (STEMI), Undergoing Primary Percutaneous Coronary Intervention (PCI)
• Official Title: Standard (180mg) Versus Double (360mg) Loading Dose of Ticagrelor in Patients With ST-elevation Myocardial Infarction (STEMI), Undergoing Primary Percutaneous Coronary Intervention (PCI): a Multi-center Randomized Parallel Pharmacodynamic Study.

Brief Summary

This is a multi-center, prospective, randomized, single-blind, investigator initiated, pharmacodynamic study of parallel design, performed at 3 institutions (Patras University Hospital; Evangelismos Athens General Hospital; Gennimatas Athens General Hospital).

Patients with ST elevation myocardial infarction (symptom onset < 12 hours), undergoing primary percutaneous coronary intervention, who are antiplatelet naïve (Group A) or present high residual PR (defined as PRU ≥ 208) immediately before primary percutaneous coronary intervention, will be randomized after informed consent, in a 1:1 ratio to either:

Ticagrelor 180mg loading dose (LD), followed by a 90mg x2 maintenance dose (MD )starting 12±6 hours post LD Or Ticagrelor 360mg loading dose (LD), followed by a 90mg x2 maintenance dose (MD) starting 12±6 hours post LD Platelet reactivity assessment will be performed at randomization (Hour 0) and at 0.5, 1, 2, 4 hours after randomization, using the VerifyNow assay, in platelet reactivity units (PRU).

Documentation of major adverse cardiac events (death, myocardial infarction, stroke, urgent revascularization procedure with PCI or CABG) and bleeding (according to Bleeding Academic Research Consortium criteria) will be performed until patient's discharge.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: ST-elevation Myocardial Infarction

Intervention

• Drug: Ticagrelor
  Ticagrelor 360mg loading dose immediately pre prior percutaneous coronary intervention 360mg loading dose
• Drug: Ticagrelor
  Ticagrelor 180mg loading dose 180mg loading dose

Study Arms

• Active Comparator: Ticagrelor 180mg loading dose
  Ticagrelor 180mg loading dose
  Intervention: Drug: Ticagrelor
• Experimental: Ticagrelor 360mg loading dose
  Ticagrelor 360mg loading dose
  Intervention: Drug: Ticagrelor

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 9, 2013): 83
• Original Estimated Enrollment (submitted: April 10, 2012): 130
• Actual Study Completion Date: February 2013
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age ≥ 18 years old
2. Patients with STEMI (onset of pain < 12 hours) with indication for primary PCI
3. Antiplatelet naïve or presenting HTPR (≥ 208 PRU) immediately before primary percutaneous coronary intervention
4. Informed consent obtained in writing

Exclusion Criteria

• Pregnancy
• Breastfeeding
• Inability to give informed consent or high likelihood of being unavailable until the Day 5
• Cardiogenic shock
• Major periprocedural complications (death, stent thrombosis, vessel perforation, arrhythmias requiring cardioversion, temporary pacemaker insertion or intravenous antiarrhythmic agents, respiratory failure requiring intubation, vascular injury (arteriovenous shunt, retroperitoneal bleeding), major bleeding (need for bood transfusion or drop in haemoglobin post-PCI by ≥ 5 gr/ dl or intracranial bleeding).
• Unsuccessful PCI (residual stenosis > 30% or flow < ΤΙΜΙ 3)
• Known hypersensitivity to ticagrelor
• History of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 3 months.
• Other bleeding diathesis, or considered by investigator to be at high risk for bleeding
• Any previous history of stroke, intracranial hemorrhage or disease (neoplasm, arteriovenous malformation, aneurysm).
• Thrombocytopenia (< 100.000/μL) at randomization
• Anaemia (Hct < 30%) at randomization
• Polycytaemia (Hct > 52%) at randomization
• Periprocedural IIb/IIIa inhibitors administration
• Thrombolysis administration
• Recent (< 6 weeks) major surgery or trauma, including GABG.
• Subjects receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors that cannot be discontinued for the duration of the study.
• Concomitant oral or IV therapy with strong CY P3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazana vir, grapefruit juice N1 L/d), CYP3A substrates with narrow therapeutic indices (cyclosporine, quinidine), or strong CYP3A inducers (rifampin/rifampicin, phenytoin, carbamazepine).
• Increased risk of bradycardiac events.
• Dialysis required.
• Severe uncontrolled chronic obstructive pulmonary disease
• Known severe hepatic impairment

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 95 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Greece

Administrative Information

• NCT Number: NCT01575795
• Other Study ID Numbers: PATRASCARDIOLOGY-10
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Dimitrios Alexopoulos, University of Patras
• Study Sponsor: University of Patras
• Collaborators: Not Provided

Investigators

• Principal Investigator: Dimitrios Alexopoulos, MD; University Hospital of Patras

• PRS Account: University of Patras
• Verification Date: April 2013