Comparison of Paclitaxel-Coated Balloons Against Drug-Eluting Bioresorbable Scaffolds for Elective PCI Using OCT

Study Overview
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Brief Summary
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This prospective randomized clinical trial aims to compare two different metal-free strategies for elective percutaneous coronary revascularization: the FFR-guided DCB-only PCI (drug-coated balloon: SeQuent Please™, B Braun Melsungen GmBH) vs. OCT-guided BRS implantation (bioresorbable scaffold: Absorb™, Abbott Vascular).

Detailed Description
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Background: Coronary artery disease (CAD) accounts for most deaths in the industrialized countries due to its high prevalence of 6-8%. CAD is mainly treated by percutaneous coronary interventions (PCI), which currently involve in over 90% of cases the implantation of metallic stents, mostly as drug-eluting devices(DES). Despite continuous technological advancement over the last decade, DES are still limited at long-term follow-up by restenosis and also by the risk of thrombosis, occurring in 5-20% and respectively 0.5-1.7% of cases. Therefore, two metal-free strategies are evaluated in order to overcome these intrinsic limitations of DES: Bioresorbable scaffolds (BRS) proved comparable safety and efficacy at 1 year compared to best-in-class DES comparators and also showed in small substudies very promising 5-year results with restoration of vasomotricity and positive vessel remodeling. Optical coherence tomography (OCT) is the new gold standard for endovascular imaging of stents, atherosclerosis progression, vulnerable plaque and neointimal proliferation. OCT is currently recommended for both guidance of implantation and for assessment of long-term results of BRS. Drug-coated balloons (DCB) were mainly employed to treat restenosis in metallic stents, but newer reports advocate their potential to be used as stand-alone treatment of de-novo stenoses without stenting, especially when fractional flow reserve (FFR) measurements are additionally used to assess PCI results. This clinical trial evaluates the FFR-guided DCB-only (experimental arm: SeQuent Please™, B Braun Melsungen GmBH) PCI against the OCT-guided BRS implantation (comparator arm: Absorb™, Abbott Vascular) for treatment of stable CAD. The trial is designed as a non-inferiority, nationally conducted, multicenter, open-labeled, controlled study using a 1:1 block randomization and am invasive 6-9 month follow-up (f/u) by quantitative coronary angiography (QCA) and OCT. Beyond the pre-specified endpoints the study mainly looking at suppression of neointimal proliferation, we will also investigate the patterns of healing and neointimal proliferation, the plaque morphology and neoatherosclerosis f/u using OCT at 6-9 months. Clinically, we attempt to record the major adverse cardiovascular events (MACE: acute myocardial infarction, cardiac death, TLR) up to 5 years after the index procedure. A number of 196 patients scheduled for PCI with a native coronary stenosis suitable for BRS implantation and OCT imaging will be openly 1:1 randomized. This number of patients is considered to be sufficient to prove non-inferiority of DCB-only vs. BRS, using a margin of 0.2 mm with a confidence interval of 0.5 mm for the primary endpoint (diameter NLG).

Official Title
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Comparison of a Paclitaxel-Coated Balloon Without Stent Implantation Against a Drug-Eluting Bioresorbable Scaffold for Treatment of Stable Coronary Artery Disease: A Prospective Randomized Study Using Optical Coherence Tomography

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: OCT-guided BRS implantation
* Device: FFR-guided DCB-only PCI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: written consent indication for elective PCI of a de novo coronary stenosis in a native vessel coronary multivessel disease with clinically proven indication for repeating coronary angiography at 6-9 months (staged PCI strategy) Exclusion Criteria: pregnancy, lactation, women of childbearing age w/o reliable contraception life expectance < 50 % at 1 year major surgery planned within 6 months participation in other clinical trials or impossibility to give written consent acute coronary syndrome or cardiogenic shock within the last 4 weeks stent thrombosis, defined as probable or definite by ARC contraindication against dual antiplatelet therapy allergy against mTOR-inhibitors or taxol derivates target lesion situated in the left main coronary artery, in a bypass graft or a grafted vessel reference luminal diameter of the target lesion > 3.75 mm or < 2.0 mm lesion length > 30 mm, bifurcation lesion requiring intervention on a major side branch

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BRS<br>OCT-guided BRS implantation: implantation of a bioresorbable scaffold (BRS) under OCT guidance. Note: Absorb™ from Abbott Vascular has been used as BRS until this product became unavailable in April 2017. Currently the recruitment is stopped due to this issue, until the use of another BRS gets final approval. | Device: OCT-guided BRS implantation<br>* Implantation of a BRS using OCT to measure vessel size, choose BRS size and length and assess implantation results and the need of further postdilations<br>|
| Experimental: DCB-only<br>FFR-guided DCB-only PCI: PCI using DCB (SeQuent Please™, B Braun Melsungen GmBH) without stent implantation und FFR guidance | Device: FFR-guided DCB-only PCI<br>* PCI performed under FFR guidance using following algorithm: (1) predilation followed by angiographic assessment of residual stenosis and dissections; (2) evaluate suitability for DCB-only, which is deemed feasible if the FFR > 0.8, residual diameter stenosis < 40% and no flow-limiting dissections are observed; (3) DCB dilation and (4) assessment of final results using FFR and QCA measurements. Provisional stenting is allowed only if the final PCI results are not acceptable (flow-limiting dissection, residual stenosis > 40% or FFR < 0.8).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Angiographic NLG | Absolute net luminal diameter gain measured by QCA as minimal luminal diameter at f/u - minimal luminal diameter at baseline within the region of interest | 6-9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volumetric NLG | Absolute net luminal volumetric gain using three-dimensional OCT-based vessel segment reconstruction at f/u | 6-9 months | 
| Angiographic and volumetric LLL | Absolute late luminal diameter loss (LLL) using QCA and late luminal volumetric loss by OCT at f/u | 6-9 months | 
| TLR | % clinically driven target lesion revascularization (TLR) during f/u | 0-9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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drug-coated balloon, bioresorbable scaffold, fractional flow reserve, optical coherence tomography