Comparison of Endothelial Dysfunction (BMS vs SES) in the Same Patient With Multiple Coronary Artery Lesions (CREDENTIAL)

Head-to-Head Comparison of Endothelial Dysfunction (Bare Metal Stent vs Sirolimus Eluting Stent) in the Same Patient With Multiple Coronary Artery Lesions

This is a prospective, randomised study to compare the endothelial dysfunction of BMS vs SES, both implanted in the same patient with multiple de novo coronary artery lesions undergoing elective PCI. The primary end point will be the evaluation of endothelial dysfunction at 6 months follow-up by measuring the change in vessel diameter in 5 points of the stent and peri-stent site after infusion of acetylcholine.

Study Overview

• Status: Completed
• Conditions: Endothelial Dysfunction
• Intervention / Treatment: Drug: intracoronary infusion of acetylcholine

Detailed Description

This prospective, randomised study compares the endothelial dysfunction of BMS vs SES, both implanted in the same patient with multiple de novo coronary artery lesions undergoing elective PCI. From february 2009 to may 2009 we aim to enroll 20 patients with at least two de novo significant angiographic stenoses in different coronary segments who will have similar diameter and length. The primary end point will be the evaluation of endothelial dysfunction at 6 months follow-up by measuring the change in vessel diameter in 5 points of the stent and peri-stent site after infusion of acetylcholine.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00151
    • Azienda Ospedaliera San Camillo Forlanini

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• stable angina pectoris
• at least two significant angiographic stenoses in different native coronary vessels or in the same vessel but two different ramifications with similar diameter
• non-surgical patients

Exclusion Criteria:

• acute coronary syndromes
• myocardial infarction within 3 months from event
• clinical or angiographic coronary vasospasm
• coronary angiographic findings of a fresh thrombus in the initial angiography (filling defect proximal to or involving the stenosis)
• coronary anatomy unsuitable for for intracoronary acetylcholine testing (left main coronary artery disease >30%, surgical three vessel disease or other anatomical considerations that make it unsafe to perform intracoronary studies)
• progression of lesions or development of de novo lesions in nontarget lesions or vessels on follow-up angiography
• patients with a vessel diameter < 2,50 mm and length lesions <10 and >30 mm.
• patients with vessel diameter difference (SES vs BMS) >0,5mm and length difference of the stenosis >50%
• lesions treated with balloon injury <10 mm or >50 mm in length
• severe left ventricular (LV) systolic dysfunction
• bifurcation/ostial
• presence of an unhealed dissection identified by intravascular ultrasound (IVUS) performed at the end of the study.
• angiographic restenosis in follow-up angiography
• patients with severe risk factors for endothelial dysfunction: severe renal failure, life expectancy less than 1 year, uncontrolled diabetes, uncontrolled hypertension (systolic blood pressure >180mmHg), currently smoking, uncontrolled hypercholesterolemia (total cholesterol >240mg/dl)
• any contraindication/nontolerance to the use of aspirin, heparin and/or clopidogrel
• lack of consent to participate

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: BMS arm; bare metal stent arm	Drug: intracoronary infusion of acetylcholine; Acetylcholine will be infused at a concentration of 140 microg/minute, over a period of 2 minutes, yielding estimated intracoronary concentrations of 10(-5)mol/L, with the assumption of a flow rate of 80mL/min). All infusions will be delivered at a constant rate using an infusion pump. Subsequently, in order to evaluate the endothelium-independent vasomotor response, 2mg of isosorbide dinitrate or bolus 250microg of nitroglycerine will be infused by intracoronary bolus in all subjects. The response to nitrate will be recorded 1 minute after the bolus. A 3-min period will be allowed to elapse between each drug infusion.; Other Names: cypher coroflex
Active Comparator: SES arm; sirolimus eluting stent arm	Drug: intracoronary infusion of acetylcholine; Acetylcholine will be infused at a concentration of 140 microg/minute, over a period of 2 minutes, yielding estimated intracoronary concentrations of 10(-5)mol/L, with the assumption of a flow rate of 80mL/min). All infusions will be delivered at a constant rate using an infusion pump. Subsequently, in order to evaluate the endothelium-independent vasomotor response, 2mg of isosorbide dinitrate or bolus 250microg of nitroglycerine will be infused by intracoronary bolus in all subjects. The response to nitrate will be recorded 1 minute after the bolus. A 3-min period will be allowed to elapse between each drug infusion.; Other Names: cypher coroflex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluation of endothelial dysfunction at 6 months follow-up by measuring the change in vessel diameter in 5 points of the stent and peri-stent site after infusion of acetylcholine	evaluation of change in vessel diameters (vasoconstriction or vasodilatation) in proximal and distal stent territories, after intracoronary acetylcholine infusion, having as reference the baseline diameters, for the BMS artery vs the SES artery	6 months

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera San Camillo Forlanini
• Investigators: Study Chair: Violini Roberto, MD, Azienda Ospedaliera San Camillo Forlanini; Principal Investigator: Mischie Nicolae Alexandru, MD, European Society of Cardiology; Study Director: Nazzaro Marco, MD, Azienda Ospedaliera San Camillo Forlanini

Publications and helpful links

General Publications

• Mischie AN, Nazzaro MS, Fiorilli R, De Felice F, Musto C, Confessore P, Parma A, Boschetti C, Violini R. Head-to-head comparison of sirolimus-eluting stent versus bare metal stent evaluation of the coronary endothelial dysfunction in the same patient presenting with multiple coronary artery lesions: the CREDENTIAL study. Catheter Cardiovasc Interv. 2013 Sep 1;82(3):E184-91. doi: 10.1002/ccd.24844. Epub 2013 Mar 5.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: November 16, 2010
• First Submitted That Met QC Criteria: November 16, 2010
• First Posted (Estimate): November 17, 2010

Study Record Updates

• Last Update Posted (Estimate): November 17, 2010
• Last Update Submitted That Met QC Criteria: November 16, 2010
• Last Verified: April 1, 2009

More Information

Terms related to this study

• Keywords: endothelial dysfunction acetylcholine bms ses
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Cholinergic Agents; Cholinergic Agonists; Acetylcholine
• Other Study ID Numbers: CREDENTIAL