PAclitaxel-eluting Balloon in Primary PCI in Amsterdam; Pilot Study

Study Overview
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Brief Summary
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This clinical evaluation will study the feasibility and safety of a CE-marked paclitaxel-eluting balloon in primary PCI in patients with a STEMI. Drug eluting balloons provide the potential advantage of delivering a anti-proliferative drug, without the disadvantage of leaving a coronary stent, in STEMI patients treated with primary PCI.

Detailed Description
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Multiple randomized clinical trials and pooled analyses have shown improved clinical outcomes of primary PCI when compared with fibrinolytic therapy. Primary PCI for STEMI results in greater patency of the infarct-related artery (IRA) and lower rates of death, re-infarction, and stroke when compared with fibrinolysis. The use of coronary stents has reduced the need for repeat revascularization in patients treated with primary PCI. However, in the setting of STEMI this reduction in target lesion revascularization (TLR) did not reduce re-infarction rates or both short term and long-term mortality rates. This was confirmed by a large meta-analysis by De Luca et al, using 13 randomized trials and involving 6922 patients. In studies evaluating DES versus BMS in STEMI mortality rates are similar in patients treated with BMS or DES. Although TLR rates are reduced with the use of DES, there have been concerns about long-term delay of arterial healing produced by both the Cypher DES and Taxus DES and the associated risk of late stent thrombosis. Anti-proliferative drugs in DES used to prevent neointimal hyperplasia also prevent the formation of an epithelial surface at the inner side of stents causing possible stent malapposition and potentionally late stent thrombosis. A new approach in treatment of STEMI is now available by the development of a drug eluting balloon. These DEB can be used with or without additional stent placement. Potential advantages compared to DES are a more homogeneous drug distribution, short lasting exposure and a higher local drug dose. Moreover, when no additional stent is needed, it might reduce the need for long term aggressive anti-platelet therapy in order to prevent acute, late or very late stent thrombosis. In short, DEB provides the potential advantage of delivering a anti-proliferative drug, without the disadvantage of leaving a coronary stent, in STEMI patients treated with primary PCI. The use of DEB is already tested for treatment of de novo coronary lesions and in-stent restenosis and has been shown to be a feasible and safe.In this clinical evaluation the use of the CE-marked Paclitaxel-eluting balloon with provisional stenting for STEMI will be evaluated on top of current highest standard therapy.

Official Title
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Pilot Study on PAclitaxel-eluting Balloon in Primary PCI in Amsterdam. A Clinical Evaluation, to Study the Feasibility and Safety of a Paclitaxel-eluting Balloon in Primary Percutaneous Coronary Intervention for Acute ST-elevation Myocardial Infarction.

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Procedure: Percutaneous coronary intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute myocardial infarction eligible for primary PCI: 20 min of chest-pain and at least 1 mm ST-elevation in at least two contiguous leads, a new left bundle branch block or a true posterior myocardial infarction reperfusion is expected to be feasible within 12 hours after onset of complaints Infarct related artery eligible for PPCI including stent implantation. Diameter of IRA ≥ 2.5 mm, ≤ 4 mm. Infarction is caused by a de novo lesion in a native coronary artery Exclusion Criteria: Age < 18 Reperfusion not feasible within 12 hours after onset of complaints Failed thrombolysis Infarct related artery unsuitable for PCI Sub-acute stent thrombosis STEMI caused by in-stent re-stenosis Infarct related vessel / target vessel SVG or LIMA Contraindication or resistance for bivalirudin, fondaparinux ,aspirin, clopidogrel and/or prasugrel. Participation in another clinical study, interfering with this protocol Cardiogenic shock prior to inclusion Uncertain neurological outcome e.g. resuscitation Intubation/ventilation Known intracranial disease (mass, aneurysm, AVM, hemorrhagic CVA, ischemic CVA/TIA < 6 months prior to inclusion or ischemic CVA with permanent neurological deficit) Gastro-intestinal / urinary tract bleeding < 2 months prior to inclusion Refusal to receive blood transfusion Platelet number < 100.000 x 10^9/L Planned major surgery within 6 weeks Stent implantation < 1 month prior to inclusion Expected mortality from any cause within the next 12 months

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ST-elevated myocardial infarction<br>Those with a condition of chestpain (or equal complains) and ECG changes confirming STEMI. | Procedure: Percutaneous coronary intervention<br>* Percutaneous coronary intervention with at least use of drug-eluting balloon and if necessary cross-over to bail-out stenting with BMS.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major acute coronary event | Defined as any death in which cardiac cause can not be excluded (death due to proximate cardiac cause, unwitnessed death, death of unknown cause, all procedure-related deaths) recurrent MI in the target vessel area (if no infarct localization is identified it is regarded target vessel related) target lesion revascularization (PCI within 5mm of the balloon(stent) area borders or CABG of the target vessel) | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cross-over to bail-out stenting |  | 1, 6 and 12 months | 
| Death from any cause |  | 1, 6 and 12 months | 
| Major acute coronary event | Defined as any death in which cardiac cause can not be excluded (death due to proximate cardiac cause, unwitnessed death, death of unknown cause, all procedure-related deaths) recurrent MI in the target vessel area (if no infarct localization is identified it is regarded target vessel related) target lesion revascularization (PCI within 5mm of the balloon(stent) area borders or CABG of the target vessel) | 6 and 12 months | 
| In-hospital major acute coronary event | Defined as, in-hospital index event: any death in which cardiac cause can not be excluded (death due to proximate cardiac cause, unwitnessed death, death of unknown cause, all procedure-related deaths) recurrent MI in the target vessel area (if no infarct localization is identified it is regarded target vessel related) target lesion revascularization (PCI within 5mm of the balloon(stent) area borders or CABG of the target vessel) | index hospitalisation | 
| Recurrent MI non-target vessel related |  | 1, 6 and 12 months | 
| Target vessel revascularisation | Target vessel revascularisation, but not target lesion revasularisation (is primary outcome measure) | 1, 6 and 12 months | 
| Stroke | objectified and documented by a physician | 1, 6 and 12 months | 
| Stent thrombosis | according tot the ARC criteria | index hospitalisation, 1, 6 and 12 months | 
| NON-CABG major bleeding | as in HORIZON trial | 1 month | 
| Hemorrhagic events | according to TIMI bleeding classification | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute myocardial infarction, Primary percutaneous coronary intervention, Drug-eluting balloon, Bivalirudin