Drug-coated Balloon Versus Drug-eluting Stent in Acute Myocardial Infarction

Study Overview
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Brief Summary
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Rationale: Compared with balloon angioplasty, implantation of bare metal stents (BMS) and drug eluting stents (DES) have shown to reduce repeat target lesion revascularization in primary percutaneous coronary intervention (PPCI). However, this did not result in a reduction of mortality or recurrent myocardial infarction. Furthermore, there are concerns of the occurrence of stent thrombosis. The PAPPA-pilot study, evaluating safety and feasibility of using a drug-coated balloon (DCB) only strategy in PPCI, showed good short- and long-term clinical results, with sustained safety and efficacy at 12 months follow-up. To date little is known about the long-term effects of this treatment modality in STEMI. Besides, angiographic follow-up is of great clinical importance by giving insight on the treated infarct lesion and to assess the functional angioplasty result. Objective: This randomized controlled, non-inferiority trial is mainly designed to prospectively assess the safety and efficacy of a CE-marked paclitaxel-eluting balloon only strategy vs. third generation DES in the setting of a ST-elevation myocardial infarction (STEMI).

Detailed Description
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Rationale: Compared with balloon angioplasty, implantation of bare metal stents (BMS) and drug eluting stents (DES) have shown to reduce repeat target lesion revascularization in primary percutaneous coronary intervention (PPCI). However, this did not result in a reduction of mortality or recurrent myocardial infarction. Furthermore, there are concerns of the occurrence of stent thrombosis. The PAPPA-pilot study, evaluating safety and feasibility of using a drug-coated balloon (DCB) only strategy in PPCI, showed good short- and long-term clinical results, with sustained safety and efficacy at 12 months follow-up. To date little is known about the long-term effects of this treatment modality in STEMI. Besides, angiographic follow-up is of great clinical importance by giving insight on the treated infarct lesion and to assess the functional angioplasty result. Objective: This randomized controlled, non-inferiority trial is mainly designed to prospectively assess the safety and efficacy of a CE-marked paclitaxel-eluting balloon only strategy vs. third generation DES in the setting of a ST-elevation myocardial infarction (STEMI). Study design: This is a prospective, single center, non-inferiority, randomized controlled trial. Study population: All patients presenting with STEMI and suitable for PPCI. Intervention: PPCI will be performed according to current guidelines. After thrombus aspiration and pre-dilatation, randomization between a DCB only strategy (with bail-out stenting if indicated) and DES will be done by 1:1 ratio. Concomitant medication will be administered according current standards. Control coronary angiography, including measurement of the fractional flow reserve (FFR) of the treated lesion(s), will be performed after 9 months. Main study parameters/endpoints: The main study parameter is the fractional flow reserve at 9 months follow-up. Secondary study parameters include cardiac death, recurrent myocardial infarction in the target vessel area and ischemia driven target lesion revascularisation at 9 months.

Official Title
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Revascularization With Paclitaxel-coated Balloon Angioplasty Versus Drug-eluting Stenting in Acute Myocardial Infarction - a Randomized Controlled Trial.

Conditions
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Coronary Artery Disease, Acute Myocardial Infarction

Intervention / Treatment
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* Procedure: Treatment according arm


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 (confirmed by ECG or echocardiography) Reperfusion is expected to be feasible within 12 hours after onset of complaints Infarct related artery eligible for PPCI and: De novo lesion in a native coronary artery Reference-vessel diameter ≥ 2.5mm and ≤ 4mm Without severe calcification Without diameter stenosis of >50% (by visual assessment) after thrombus aspiration and pre-dilatation. The protocol requires visualization, thrombus aspiration and pre-dilatation of the culprit lesion before inclusion. Exclusion Criteria: Age < 18 years and > 75 years History of myocardial infarction Known contraindication/resistance for bivalirudin, fondaparinux, heparin, aspirin, prasugrel and/or ticagrelor. Participation in another clinical study, interfering with this protocol Uncertain neurological outcome e.g. resuscitation Intubation/ventilation Cardiogenic shock prior to randomization 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 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
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Drug-eluting stent<br>Treatment of infarct related laesion with a drug-eluting stent | Procedure: Treatment according arm<br> <br> |
| Experimental: Drug-coated balloon<br>After treatment of the infarct related artery with a drug-coated ballon, an additional BMS is advised to be used in case of residual stenosis > 50% or coronary artery dissection type > B. | Procedure: Treatment according arm<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractional flow reserve (FFR) | Fractional flow reserve is the ratio of mean coronary pressure distal of the treated lesion to mean aortic pressure during maximum hyperemia. | At 9 months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiac event (MACE) | Cardiac death (ARC); defined as any death in which a cardiac cause cannot be excluded. Recurrent MI in the target vessel area. Ischemia driven target lesion revascularization (PCI within 5 mm of the treated segment in case of balloon, or stent area borders in case of stent, or CABG of the target vessel). | In-hospital, at 1 and 9 months follow-up and at 2, 3, 4 and 5 year follow-up. | 
| Angiographic endpoint: iFR |  | At 9 months follow-up. | 
| ST-segment resolution | ST-segment resolution post-initial procedure at 90 minutes, defined as the ST-segment deviation resolution in only the single lead showing maximum deviation. | 90 minutes after initial procedure | 
| Non-coronary artery bypass grafting major bleeding | Intracranial, intraocular, intra-articular or retroperitoneal bleeding Access site bleed requiring intervention/surgery Hematoma ≥ 5 cm Hemoglobin (Hgb) ≥4 g/dL without an overt source Hgb ≥3 g/dL with an overt source Operation for bleeding Any blood transfusions | At 1 month follow-up | 
| Stent thrombosis | Definite or confirmed stent thrombosis: Angiographic confirmation of vessel occlusion or thrombus formation within, or adjacent to, the stented segment or proven stent thrombosis at autopsy. Probable stent thrombosis: Unexplained death within 30 days or target vessel recurrent MI without angiographic confirmation. Possible stent thrombosis: Unexplained death after 30 days. | During follow-up | 
| Angiographic endpoint: TIMI flow |  | At 9 months follow-up | 
| Angiographic endpoint: late lumen loss |  | At 9 months follow-up | 
| Angiographic endpoint: minimal lumen diameter |  | At 9 months follow-up | 
| Angiographic endpoint: diameter stenosis |  | At 9 months follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary artery disease, Acute myocardial infarction, Drug-coated balloon, Drug-eluting stent