Drug-Coated Balloon Coronary Angioplasty Versus Stenting for Treatment of Disease Adjacent to a Chronic Total Occlusion.

Study Overview
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Brief Summary
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This is an investigator-initiated, randomized, multi-center, non-inferiority clinical trial. Patients with a Chronic Total Occlusion who are eligible for PCI will be randomized to additional Drug-Coated-Balloon treatment or stenting of adjacent residual disease to the CTO body. The aim of this study is to investigate whether treatment with DCB is non-inferior to complete stenting of the CTO body.

Detailed Description
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Rationale: Chronic total coronary occlusions (CTOs) are documented in approximately 16-18% of diagnostic coronary angiograms. New developments such as retrograde approach and dissection re-entry techniques have resulted in more widespread application of percutaneous coronary intervention (PCI) of CTOs, and this technique now serves as a viable alternative to optimal medical therapy alone or coronary artery bypass surgery. In general, PCI CTO is accompanied by extensive stenting of the coronary artery beyond the original occlusive segment itself. Unfortunately, stent length and diameter are directly related to poorer outcome, which is related to an increased rate of in-stent restenosis and thrombosis. An alternative to stenting is the application of drug-coated balloons (DCB). This strategy may prove beneficial, as it could significantly reduce stent length, among other things. However, data on the use of DCBs in the context of PCI CTO are currently lacking. Objective: To investigate the value of DCB treatment in the residual disease of the coronary artery after successful recanalization and stenting of the actual CTO body as compared with complete stenting in a randomized fashion. Study design: This is an investigator-initiated, randomized, single-blind (patients will be masked), multicenter, non-inferiority clinical trial. Study population: 154 patients with a CTO eligible for PCI based on a formal local heart team decision will be screened for potential inclusion in the study. Intervention: Patients with a CTO who are eligible for PCI will be randomized in a 1:1 ratio to additional DCB treatment or stenting of residual disease. Main study parameters/endpoints: The primary endpoint is percentage diameter stenosis at 1-year follow-up as assessed by intravascular ultrasound (IVUS). Secondary invasive imaging objectives include minimal lumen diameter, late luminal loss, in-segment binary restenosis, and target vessel re-occlusion at 1-year follow-up. Secondary clinical objectives are evaluation of the occurrence of major adverse cardiac events (MACE) at 1-year follow-up. Nature and extent of the burden and risks associated with participation, benefit and group-relatedness: Participation in this study entails additional measurements, namely follow-up coronary angiography at 12 months, CCTA-scan at 12 months (if participating in substudy), and telephonic follow-up at 30 days and 12 months. All patients included in the trial will have a clinical indication for percutaneous revascularization. Since there are no randomized controlled trials which advocate the use of either DES or DCB over one another in this setting, the risk of the PCI procedure will not be related to study participation. All patients will undergo coronary angiography after 1-year follow-up and will thus be exposed to the risks of invasive coronary angiography. Coronary angiography is characterized by a low complication rate (<0.5%). Repeat angiography also carries a low amount of radiation exposure. Patients participating in the CCTA substudy will be exposed to additional radiation. The ionized contrast agents used in both coronary angiography and CCTA substudy can be nephrotoxic and can elicit allergic reactions. A DCB facilitated minimal stenting strategy for treatment of chronic total occlusions may significantly reduce stent length, number of used stents, as well as compression of the distal lumen with undersized stents. While DCB is expected to be non-inferior to DES regarding the in-segment diameter stenosis (primary endpoint), possible benefits may be observed in the secondary endpoints. Consequently, this trial could influence current guidelines on the application of DCBs in CTO procedures.

Official Title
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A Randomized, Multi-center, Non-inferiority Clinical Trial on the Treatment of Residual Disease With Drug-Coated Balloon After Successful Recanalization and Limiting Stenting to the CTO Body Compared to Complete Stenting of the CTO Body and Adjacent Residual Disease.

Conditions
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Chronic Total Occlusion of Coronary Artery

Intervention / Treatment
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* Device: Drug-Coated Balloons
* Device: Drug-Eluting-Stent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Clinical indication for revascularization of the CTO as determined by the local heart team (based on symptoms, documented ischemia, and viability) Successful recanalization of the CTO with residual disease adjacent to the initial lesion Exclusion Criteria: Dissection affecting the flow (TIMI score<3), significant recoil (>30%) or coronary perforation after predilation Reference diameter of the vessel is <2.5 mm or >4.0 mm Bifurcation lesion requiring the stenting of the side branch Left main lesion Acute coronary syndrome Cardiogenic shock Severe kidney disease defined as an eGFR < 30 ml/min Pregnancy Life expectancy < 12 months Inability to give written consent

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
Interventional Model Description: Patients with a CTO who are eligible for PCI will be randomized in a 1:1 ratio to additional DCB treatment or stenting of residual disease.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug-coated balloon<br>Patients will receive stenting of the actual CTO body with additional DCB treatment of the residual disease of the coronary artery. | Device: Drug-Coated Balloons<br>* Percutaneous coronary intervention of residual disease adjacent to a chronic total occlusion with a paclitaxel drug-coated balloon (minimal stenting strategy).<br>|
| Active Comparator: Drug-eluting stent<br>Patients will receive complete stenting of the CTO body and residual disease of the coronary artery. | Device: Drug-Eluting-Stent<br>* Percutaneous coronary intervention of the chronic total occlusion and residual coronary artery disease with an everolimus-eluting platinum chromium coronary stent (complete stenting strategy).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-segment diameter stenosis | The primary outcome is to investigate percentage diameter stenosis at 1-year follow-up as assessed by intravascular ultrasound (IVUS). | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive | Minimal lumen diameter (millimeters) Late luminal loss (millimeters) In-segment binary restenosis (>50%) Target vessel re-occlusion (yes/no) | 1 year | 
| Clinical (MACE) | Major adverse cardiac events (MACE). MACE is composite endpoint of cardiac death, non-fatal myocardial infarction and ischemia driven target lesion revascularization (ID-TLR) | 1 year | 
| Clinical (angina) | Occurrence of angina pectoris according to the Canadian Cardiovascular Society Grading Scale (grade 1-4): Angina only during strenuous or prolonged physical activity; Slight limitation, with angina only during vigorous physical activity; Symptoms with everyday living activities, i.e. marked limitation; Inability to perform any activity without angina or angina at rest, i.e. severe limitation. | At inclusion and 1-year follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug-coated balloon, Drug-eluting stent, Randomized controlled trial, PCI