High Clopidogrel Dose Versus Prasugrel and Ticagrelor in High Reactive Stable Patients (TRIPLETE RESET)

Comparison of Therapy With TICAGRELOR, Prasugrel and High Clopidogrel Dose in PCI Patients With High on Treatment Platelet Reactivity and Genotype Variation

Dual antiplatelet therapy with Aspirin and Clopidogrel for at least one year is essential in patients following an acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) with drug eluting stent(s) implantation. Interindividual variability in platelet response to Clopidogrel has been reported, with several mechanisms (intrinsic high platelet reactivity [PR], variability of the drug metabolism, and various drug interactions) being implicated for high post-Clopidogrel treatment PR. The investigators aim to perform a prospective, single-center, investigator-initiated, randomized, study to compare platelet inhibition by Prasugrel 10 mg/day, Ticagrelor (90 mg twice daily) and high-dose 150 mg/day Clopidogrel in patients with High on-treatment platelet reactivity (HTPR) with standard dose of Clopidogrel. Patients with HTPR (defined as area under curve-AUC ≥ 450 or > 45 Unit) and with loss-of-function allele CYP2C19*2 will be enrolled in the study and will be randomized (Day 0) in a 1:1:1 ratio, to either Clopidogrel 150 mg a day or Prasugrel 10 mg a day or Ticagrelor (90 mg twice daily) until Day-15 and-30 post randomization.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Prasugrel; Drug: Clopidogrel; Drug: Ticagrelor

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 000161
    • Dept.of Cardiovascular Sciences,Policlinico Umberto I

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients underwent to percutaneous coronary intervention (PCI)
• clopidogrel resistance after Platelet reactivity blood test

Exclusion Criteria:

• history of bleeding diathesis
• chronic oral anticoagulation treatment
• contraindications to antiplatelet therapy
• PCI or coronary artery bypass grafting (CABG) < 3 months
• hemodynamic instability
• platelet count < 100,000/μl
• hematocrit < 30%
• creatinine clearance < 25 ml/min
• Patients with a history of stroke
• contraindication for prasugrel administration
• patients weighing < 60 kg
• > 75 years of age.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prasugrel standard dose; Patient will be randomized to this intervention will receive in the first time prasugrel and after 15 days and 30 days we will control the responsivness of the study drug.	Drug: Prasugrel; Patient will be randomized to this intervention will receive in the first time prasugrel and after 15 days and 30 days we will control the responsivness of the study drug.
Experimental: high clopidogrel dose; Patient will be randomized to this intervention will receive in the first time the high clopidogrel dose and after 15 days and 30 days we will control the responsivness of the study drug.	Drug: Clopidogrel; Patient will be randomized to this intervention will receive in the first time the double dose of clopidogrel and after 15 days and 30 days we will control the responsivness of the study drug.
Experimental: Ticagrelor standard dose; Patient will be randomized to this intervention will receive in the first time ticagrelor and after 15 days and 30 days we will control the responsivness of the study drug.	Drug: Ticagrelor; Patient will be randomized to this intervention will receive in the first time Ticagrelor and after 14 days and 28 days we will change their therapy with the high clopidogrel dose or Prasugrel (dual crossover).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
antiplatelet effect of standard dose of prasugrel or ticagrelor versus high dose clopidogrel in stable patients with high reactivity	the antiplatelet effect in terms of level platelet reactivity (< 450 Area under the curve (AU*min)) of standard dose of Prasugrel (10 mg/day) either Ticagrelor (90 mg twice daily) versus high dose Clopidogrel (150 mg/day) in patients undergoing PCI with high reactivity	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding (major, minor, or minimal)	Bleeding (major, minor, or minimal)	45 days
Major Adverse Cardiac Cerebrovascular Events	cardiovascular death, myocardial infarction, and stroke	45 days

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza

Publications and helpful links

General Publications

• Sardella G, Calcagno S, Mancone M, Lucisano L, Pennacchi M, Stio RE, Placentino F, Di Roma A, Cavallo E, Palmirotta R, Guadagni F, Fedele F. Comparison of therapy with Ticagrelor, Prasugrel or high Clopidogrel dose in PCI patients with high on treatment platelet reactivity and genotype variation. TRIPLETE RESET trial. Int J Cardiol. 2015 Sep 1;194:60-2. doi: 10.1016/j.ijcard.2015.05.085. Epub 2015 May 15. No abstract available.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: February 21, 2012
• First Submitted That Met QC Criteria: March 2, 2012
• First Posted (Estimate): March 5, 2012

Study Record Updates

• Last Update Posted (Estimate): December 11, 2013
• Last Update Submitted That Met QC Criteria: December 10, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: stable angina; prasugrel; clopidogrel; antiplatelet effect
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel; Prasugrel Hydrochloride
• Other Study ID Numbers: TRIPLETE RESET