Clinical trial NCT01805570: Rapid Activity of Platelet Inhibitor Drugs Study 2
Official title: Rapid Activity of Platelet Inhibitor Drugs Study (RAPID 2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myocardial Infarction
Keywords: platelet inhibitor
ST-segment Elevation
Myocardial Infarction
stent
prasugrel
ticagrelor
Lead sponsor: Careggi Hospital
Sponsor class: OTHER
Collaborators: name: A.R. CARD Onlus Foundation
First posted: 2013-03-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the RAPID study is to evaluate the superiority rapid onset of action of Ticagrelor 360 mg LD versus Prasugrel 60 mg LD, in 50 patients with STEMI (ST segment elevation myocardial infarction) undergoing PPCI with bivalirudin monotherapy. Secondary study aim is to found out clinical predictors of high residual platelet reactivity in the first hour after a novel oral antiplatelet agent LD.

Detailed description: 50 consecutive patients with STEMI undergoing PPCI with bivalirudin (GP IIb/IIIa not allowed) will be randomized to receive Prasugrel (n= 25) or Ticagrelor (n= 25) before PPCI ( primary percutaneous coronary intervention) in a open label fashion. The loading dose of Prasugrel will be 60 mg, the loading dose of Ticagrelor will be 360 mg in 25 patients. The loading dose will be performed as soon as possible in the Emergency Room or in the Cath Lab. In the case of vomit in the first hour after drug loading dose a new reduced loading dose will be administered (30 mg Prasugrel or 180 mg Ticagrelor). All interventions will be performed by the femoral approach according to current standards. The use of thrombectomy before infarct-related artery stenting, of everolimus eluting stent and of closure devices will be strongly encouraged. Bivalirudin will be administered as a bolus 0.75 mg/kg followed by 1.75 mg/kg/h infusion during PCI. After PCI (percutaneous coronary intervention) a reduced bivalirudin infusion of 0.25 mg/kg/h for 4 hours will be allowed. Dual antiplatelet therapy (100 mg aspirin associated with 5 or 10 mg Prasugrel or 180 mg Ticagrelor) will be recommended for 12 months.

Residual platelet reactivity will be assessed in all patients at baseline (time of LD), and after 1, 2, 4 and 12 hours by a point-of-care test VerifyNow bedside available in the Intensive cardiac care Unit. High residual platelet reactivity will be defined as a Platelet Reactivity Units (PRU) \> 240 by VerifyNow. At the same time point, Aspirin Reactivity Units (ARU) by VerifyNow will be also assessed. Follow-up will be performed by outpatient visits or telephone interviews at 6 months.

Eligibility criteria: Inclusion Criteria:

* Patients presenting within 12 hours from the onset of symptoms with STEMI (ST segment elevation myocardial infarction)
* Informed, written consent

Exclusion Criteria:

* Age \< 18 years or Age \> 75 years
* Active bleeding; bleeding diathesis; coagulopathy
* Increased risk of bradycardiac events
* History of gastrointestinal or genitourinary bleeding \<2 months
* Major surgery in the last 6 weeks
* History of intracranial bleeding or structural abnormalities
* Suspected aortic dissection
* Any previous TIA (transient ischemic attack)/stroke
* Any other condition that may put the patient at risk or influence study results or investigator's opinion (severe haemodynamic instability, known malignancies or other comorbid conditions with life expectancy \<1 year)
* Administration in the week before the index event of clopidogrel, ticlopidine, prasugrel, ticagrelor, thrombolytics, bivalirudin, low-molecular weight heparin or fondaparinux .
* Concomitant oral or IV therapy with strong CYP3A inhibitors or strong CYP3A inducers, CYP3A with narrow therapeutic windows
* Known relevant hematological deviations: Hb \<10 g/dl, Platelet count \<100x10\^9/l
* Use of coumadin derivatives within the last 7 days
* Chronic therapy with prasugrel or ticagrelor
* Known severe liver disease, severe renal failure
* Known allergy to the study medications

Primary outcomes:
measure: Residual Platelet Reactivity by VerifyNow
timeFrame: 1 hour
Secondary outcomes:
measure: High residual platelet reactivity
timeFrame: 2,4,12 hours
Other outcomes:
Locations:
city: Florence
country: Italy
facility: Careggi Hospital
Study officials:
affiliation: Careggi Hospital, Division of Invasive Cardiology
name: David Antoniucci, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Parodi G, Bellandi B, Valenti R, Migliorini A, Marcucci R, Carrabba N, Giurlani L, Gensini GF, Abbate R, Antoniucci D. Comparison of double (360 mg) ticagrelor loading dose with standard (60 mg) prasugrel loading dose in ST-elevation myocardial infarction patients: the Rapid Activity of Platelet Inhibitor Drugs (RAPID) primary PCI 2 study. Am Heart J. 2014 Jun;167(6):909-14. doi: 10.1016/j.ahj.2014.03.011. Epub 2014 Apr 4.