High Clopidogrel Dose Versus Prasugrel and Ticagrelor in High Reactive Stable Patients

NCT01543932 | Completed Phase 3 DMC

• 1 other identifier: TRIPLETE RESET
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Coronary Artery Disease

Keywords

antiplatelet effect; prasugrel; clopidogrel; stable angina

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Bleeding (major, minor, or minimal)

  45 days

• Major Adverse Cardiac Cerebrovascular Events

  45 days

Study Arms (3)

Prasugrel standard dose

EXPERIMENTAL

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

high clopidogrel dose

EXPERIMENTAL

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

Ticagrelor standard dose

EXPERIMENTAL

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

Interventions

Clopidogrel DRUG

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.

high clopidogrel dose

Prasugrel DRUG

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.

Prasugrel standard dose

Ticagrelor DRUG

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).

Ticagrelor standard dose

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Study Sites (1)

Dept.of Cardiovascular Sciences,Policlinico Umberto I

Rome, Rome, 000161, Italy

Location

Related Publications (1)

• 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.

  PMID: 26011265 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Angina, Stable

Interventions

Clopidogrel; Prasugrel Hydrochloride; Ticagrelor

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Angina Pectoris; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Piperazines; Adenosine; Purine Nucleosides; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor in Cardiology

Study Record Dates

• First Submitted: February 21, 2012
• First Posted: March 5, 2012
• Study Start: July 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 11, 2013

Record last verified: 2013-12

Locations

IT (1)