Effects of DES Platforms on Markers of Endothelial Damage and Inflammation

Phase 4

• Conditions: Coronary Artery Disease
• Interventions: Device: platinum chromium everolimus-eluting stent; Device: cobalt chromium everolimus-eluting stent

• Registration Number: NCT01489202
• Lead Sponsor: University of Roma La Sapienza

Brief Summary

Percutaneous coronary intervention (PCI) with stenting may induce endothelial damage/dysfunction and inflammatory reactions, which in turn delay healing and endothelialization and may lead to restenosis and atherosclerosis within the stented segments. Drugs and polymers are considered the protagonists of these pathophysiologic processes whereas the role of stent platforms remains poorly defined.It remains unknown, conversely, if stent platforms affect the extent of post-PCI endothelial damage and inflammation.

Detailed Description

Percutaneous coronary intervention (PCI) with stenting may induce endothelial damage/dysfunction and inflammatory reactions, which in turn delay healing and endothelialization and may lead to restenosis and atherosclerosis within the stented segments.

Drugs and polymers are considered the protagonists of these pathophysiologic processes whereas the role of stent platforms remains poorly defined.

Due to advances in stent technology, stent platforms have evolved from the cobalt-chromium (CoCr) to the platinum-chromium (PtCr) stent series. At present, the PROMUS Element stent (which uses the PtCr platform) employs an identical polymer, drug, drug formulation and dose density to the CoCr XIENCE V stent.

The PLATINUM WH trial is the only randomized trial comparing the PROMUS Element stent with the XIENCE V stent in a total of 1,530 patients. The study met its primary end-point demonstrating that the PROMUS Element stent is non-inferior to the XIENCE V stent. The 12-month rare of target lesion failure was 3.4% in the PROMUS Element stent and 2.9% in the XIENCE V stent.

Pre-clinical animal studies, however, suggest that the PtCr platform might have important advantages over the CrCo platform, as improved vascular compatibility and early and late healing for PtCr devices compared with CoCr stents have been demonstrated.

In a rabbit denudation model, it was shown that at 14 days the luminal surface area is incompletely endothelialised with the CrCo stents but nearly complete for the PtCr stents. Similarly, another experimental study has shown that overall strut coverage, including endothelial cell coverage plus non-endothelial cell coverage (focal platelet and fibrin aggregates inter-mixed with red blood cells and inflammatory cells), is significantly lower at 14 days with the CoCr stent than with the PtCr OMEGA stent. Additionally, a recent investigation has shown that the thinner-strut PtCr stent is associated with reduced fibrin deposition and more rapid fibrin clearance in porcine coronary arteries compared with CrCo stent, thus suggesting that the PtCr stent platform may induce less injury compared with previous-generation platforms.

The primary objective of this study is to perform a randomized comparison of the biohumoral effects of platinum chromium everolimus-eluting stent (PtCr EES) vs. cobalt chromium everolimus-eluting stent (CoCr EES), i.e. stents with different platforms but identical drug and polymer.

Study Timeline

• Study First Submitted: 2011-12-06
• Study First Submitted QC: 2011-12-08
• Study First Posted: 2011-12-09
• Status Verified: 2013-03
• Last Update Submitted: 2013-03-06
• Last Update Posted: 2013-03-07
• Study Start: 2014-09
• Primary Completion: 2015-12
• Study Completion: 2016-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• A de novo native coronary artery lesions (reference vessel diameter:2.5-3.75 mm)
• Class I indication to elective percutaneous coronary intervention
• Stable conditions and no recent acute coronary syndromes
• Normal baseline values of markers of myocardial damage (creatine kinase, creatine kinase-MB, myoglobin, and troponin I)
• Able to understand and willing to sign the informed CF

Exclusion Criteria

• Women of child bearing potential patients must demonstrate a negative pregnancy test performed within 24 hours before CT

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
platinum chromium EES	platinum chromium everolimus-eluting stent	Patients undergoing PCI with stenting will have implantation of platinum chromium everolimus-eluting stents
cobalt chromium everolimus-eluting stent	cobalt chromium everolimus-eluting stent	Patients undergoing PCI with stenting will have implantation of cobalt chromium everolimus-eluting stents

Primary Outcome Measures

Name	Time	Method
Post-PCI changes in markers of endothelial damage	Baseline and 24 hours after PCI	Changes 24 hours after PCI in the following indexes of endothelial damage: 1. von Willebrand Factor (vWF); 2. sE-selectin; 3. Vascular cell adhesion molecule (sVCAM-1); 4. Intercellular adhesion molecule (sICAM-1)
Post-PCI changes in markers of inflammation	Baseline and 24 hours after PCI	Changes 24 hours after PCI in the following inflammatory markers: 1. C-reactive protein (CPR); 2. Fibrinogen; 3. Plasminogen activator inhibitor (PAI-1); 4. Interleukin-6 (IL-6)

Secondary Outcome Measures

Name	Time	Method
12-month rate of MACE	Up to 12 months	12-months incidence of major adverse cardiac events (MACE-death, myocardial infarction, target vessel revascularization)

Trial Locations

Locations (1)

University La Sapienza; 🇮🇹 Rome, Italy