Comparative Response to Vascular Injury in Patients With Diabetes Mellitus: An OCT Study of BVS Versus Xience DES

Stents are used at centers around the world to unblock the arteries of the heart. These stents are usually made of metal and remain permanently within the blood vessel wall. Newer developments in the stent technology has led to stent scaffolds that can be reabsorbed over time. Patients with diabetes are prone to more complex blockages in the heart arteries which can be more difficult to treat. The purpose of this study is to compare the difference of how arteries heal early when metal stents or resorbable stents are used in patients with diabetes.

Study Overview

• Status: Withdrawn
• Conditions: Coronary Artery Disease; Diabetes Mellitus
• Intervention / Treatment: Device: Xience Drug Eluting Stent; Device: ABSORB Bioresorbable Vascular Scaffold

Detailed Description

Coronary revascularization by percutaneous coronary intervention (PCI) is the dominant strategy in patients with obstructive coronary artery disease (CAD). Traditionally, PCI is performed with implantation of one or more permanent metallic stents which act as a scaffold for arterial recoil and, in the case of drug eluting stents (DES), provide a platform for delivery of anti-proliferative agents. A recent innovation in coronary stent technology is the advent of a bioresorbable vascular scaffold (BVS) - a poly L-lactide (PLLA) scaffold covered with a poly D,L-lactide coating which elutes everolimus. Bioresorption occurs by de-esterification of the long chains of PLLA into small particles which are then phagocytosed by macrophages. Within two years, the BVS is completely resorbed and vasomotor reactivity of the blood vessel is restored.

Patients with diabetes mellitus (DM) represent a clinically challenging population - having an increased incidence of complex CAD as well as higher rates of stent thrombosis (ST) and in-stent restenosis (ISR) following PCI. ST occurs most frequently in the first thirty days following stent implantation and is prevented by effective antiplatelet medications, optimization of stent deployment and by rapid reendothelialization (RE) of the device. Notably, patients with DM have delayed RE following stent implantation which results in a marked increase in risk of ST. Thus, patients with DM in particular are in need of devices that result in rapid establishment of stent coverage by optimizing the response to vascular injury.

Our study aims to answer the question: "Are there important differences in early healing between BVS and DES in patients with DM?" Our study hypothesis is that a BVS platform will enhance vascular healing resulting in greater strut coverage by 6 weeks in patients with DM.

This is a single centre, interventional, prospective cohort study which will be conducted between July 2017 and July 2019. A total of 52 patients will be recruited for participation in this study. Stable patients with diabetes will undergo randomization to either BVS or DES in the first target lesion using optical coherence tomography (OCT) at the time of the index procedure. Subsequently, patients will undergo staged PCI at four or six weeks (sub-randomization) of the second lesion with OCT evaluation of the initially implanted device to determine the percent of uncovered struts.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Stable patients with diabetes mellitus
2. Two or more stenoses in a major epicardial native coronary artery
3. An indication for PCI (i.e. >70% on angiography or fractional flow reserve (FFR) <0.8)
4. Coronary anatomy suitable for a BVS

Exclusion Criteria:

1. Unwillingness or inability to provide informed consent.
2. ST-elevation myocardial infarction
3. Hemodynamic instability

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Xience Drug Eluting Stent; Patients with diabetes mellitus will be randomized to receive either a Xience drug eluting stent or an ABSORB bioresorbable vascular scaffold for treatment of obstructive coronary artery disease	Device: Xience Drug Eluting Stent; Patients will undergo insertion of a drug eluting stent with assessment of strut coverage using optical coherence tomography at 4 to 6 weeks after implantation.
ACTIVE_COMPARATOR: ABSORB Bioresorbable Vascular Scaffold; Patients with diabetes mellitus will be randomized to receive either a Xience drug eluting stent or an ABSORB bioresorbable vascular scaffold for treatment of obstructive coronary artery diseasee	Device: ABSORB Bioresorbable Vascular Scaffold; Patients will undergo insertion of a bioresorbable vascular scaffold with assessment of strut coverage using optical coherence tomography at 4 to 6 weeks after implantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of uncovered struts at time of follow-up optical coherence tomography	The primary outcome will be the percent of uncovered struts analyzed at 5mm segments using a standardized protocol for optical coherence tomography at time of staged percutaneous coronary intervention procedure	4 to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late lumen loss	Assessment of standardized lumen area at 5mm increments	4 to 6 weeks
Neointimal area:artery area	Assessment of standardized neointimal area:artery area at 5mm increments	4 to 6 weeks
Strut malapposition	Assessment of strut malapposition as a percentage of total struts	4 to 6 weeks
In-stent restenosis	Binary in-stent restenosis defined as greater than 50% in-stent lumen loss	4 to 6 weeks
Target lesion revascularization	Any intervention within 5mm of the study device	4 to 6 weeks
Major adverse cardiac events	A composite of death, myocardial infarction or stroke	4 to 6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subgroup analysis between 4 and 6 weeks	A subgroup analysis between four and six weeks will be performed to study the gradation of intimal response during early vascular healing	4 to 6 weeks

Collaborators and Investigators

• Sponsor: Ottawa Heart Institute Research Corporation

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 1, 2017
• Primary Completion (ANTICIPATED): July 1, 2019
• Study Completion (ANTICIPATED): July 1, 2019

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: July 31, 2017
• First Posted (ACTUAL): August 1, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 19, 2017
• Last Update Submitted That Met QC Criteria: October 18, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Wounds and Injuries; Endocrine System Diseases; Coronary Disease; Coronary Artery Disease; Diabetes Mellitus; Vascular System Injuries
• Other Study ID Numbers: 20170128-01H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes