Evaluation of Platelet Function After Statin Loading Dose in Patients Before Percutaneous Coronary Intervention (STATIPLAT)

Prospective, Randomized, Single Center, Open Label Study Designed to Evaluate the Effect on Platelet Reactivity in Response to High Doses of Atorvastatin or Rosuvastatin Administered Before Percutaneous Coronary Intervention (PCI)

The purpose of this study is to evaluate the effect of a loading dose of two different statins on platelet reactivity (atorvastatin, metabolized by CYP3A4, and rosuvastatin, which is rather independent of this enzyme)in patients at least 5 days in therapy with aspirin and clopidogrel (with or without an undergoing treatment with statins) undergoing PCI for coronary disease with chronic stable angina and/or evidence of inducible myocardial ischemia.

Study Overview

• Status: Completed
• Conditions: Platelet Dysfunction
• Intervention / Treatment: Drug: Atorvastatin; Drug: Rosuvastatin; Drug: Placebo

Detailed Description

An initial assessment of platelet reactivity in response to the TRAP (thrombin receptor agonist), ADP and arachidonic acid (respectively, indicative of the response to clopidogrel and aspirin) will be performed with impedance aggregometry (Multiplate® analyzer system). Patients with a increased residual platelet reactivity to ADP test (AUC > 47) will receive a different antiplatelet therapy and will then be excluded from the study, the other will be randomized to 3 groups of treatment.

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20132
    • IRCCS San Raffaele Monte Tabor

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:

• Age: 18-75 years
• Patients with chronic stable angina
• Patients with coronary artery disease or with de novo stent restenosis of native vessels.
• Patients who are able to understand the significance of this study and to adhere to recruitment by signing the informed consent.

Exclusion Criteria:

• Acute Coronary Syndromes with an enzymatic movement (STEMI, NSTEMI).
• Allergy or intolerance to atorvastatin, rosuvastatin, aspirin, clopidogrel.
• Altered basal level of transaminase or CPK.
• Patient with history of hepatitis-acute/chronic.
• Patients already receiving high-dose statins.
• Contraindications to antiplatelet therapy.
• Patients with acute inflammatory disease and/or underlying chronic (hepatitis, pneumonia, urinary tract, rectum ulcerative colitis etc.).
• Patients with anemia (haemoglobin <8.5 mg/dl), leukocytosis (WBC> 12.000 mm3), leukopenia (WBC <3000 mm3), platelet count <100.000; hypersplenism.
• Patients with malignant disease.
• Patients enrolled in other studies not yet completed.
• Patients with known allergy / intolerance to statins.
• Pregnant women and women who are breastfeeding.
• Patients with myopathy (muscle pain and unexplained repeated)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Atorvastatin; Atorvastatin 80 mg	Drug: Atorvastatin; 80 mg; Other Names: TORVAST; TOTALIP
ACTIVE_COMPARATOR: Rosuvastatin; Rosuvastatin 40 mg	Drug: Rosuvastatin; 40 mg; Other Names: CRESTOR
PLACEBO_COMPARATOR: No statin loading dose	Drug: Placebo; no statin loading dose; Other Names: NO STATIN DRUGS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Aggregation Curve (AUC) measured with the Multiplate 5.0 Analyzer	Evaluation of the effect of a loading dose (LD) of two different statins on platelet reactivity (atorvastatin and rosuvastatin) in terms of difference between AUC value before statin LD and after 12 hrs statin LD. The Area Under the Aggregation Curve (AUC) will be measured with the Multiplate 5.0 system.	Evaluation of platelet reactivity (in terms of AUC) two time points.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of periprocedural myocardial infarction	To evaluate if the loading dose of statin prevent the periprocedural myocardial damage measured by CK and CK-MB The measurments will be done once before the procedure and at 6 and 12 hours after.	CK and CK-MB evaluated before the procedure and two time points up to 12 hours

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele
• Investigators: Principal Investigator: Antonio Colombo, MD, IRCCS San Raffaele Monte Tabor

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (ACTUAL): February 1, 2014
• Study Completion (ACTUAL): February 1, 2014

Study Registration Dates

• First Submitted: September 14, 2011
• First Submitted That Met QC Criteria: February 2, 2012
• First Posted (ESTIMATE): February 3, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): March 6, 2014
• Last Update Submitted That Met QC Criteria: March 5, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Atorvastatin; Platelet; Rosuvastatin; Multiplate; reactivity
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Rosuvastatin Calcium
• Other Study ID Numbers: STATIPLAT