Critical Limb-Threatening Ischaemia, Drug Coated Balloon, Femoropopliteal Disease, Peripheral Arterial Disease
Conditions
Keywords
Chronic Limb-Threatening Ischaemia (CLTI), Peripheral Artery Disease (PAD), Femoropopliteal Disease, Drug-Coated Balloon (DCB), Vessel Preparation, Scoring Balloon, Non-Compliant Balloon, Primary Patency, Bailout Stenting
Brief summary
The aim of this clinical trial is to determine whether vessel preparation with a non-compliant scoring balloon before drug-coated balloon (DCB) angioplasty provides superior procedural and clinical outcomes compared with vessel preparation using a non-compliant plain balloon in patients with chronic limb-threatening ischaemia (CLTI) undergoing femoropopliteal endovascular intervention. The main questions the study aims to answer are: * Does non-compliant scoring balloon vessel preparation reduce the need for bailout stenting during the index procedure? * Does it improve primary patency after DCB angioplasty? * Does it improve clinically relevant outcomes such as wound healing, freedom from clinically driven target lesion revascularisation, limb salvage and health-related quality of life? * Does it provide procedural and economic advantages compared with non-compliant plain balloon vessel preparation? Participants will be randomly assigned to undergo vessel preparation using either a non-compliant plain balloon or the DKutting™ non-compliant scoring balloon, followed by angioplasty with the Legflow XP™ drug-coated balloon. Patients will undergo clinical, duplex ultrasound and quality-of-life follow-up for 24 months.
Detailed description
The DASBAD-NC trial is a prospective, multicentre, randomised, patient-blinded, controlled clinical investigation designed to compare two vessel preparation strategies before drug-coated balloon (DCB) angioplasty for femoropopliteal arterial disease in patients with chronic limb-threatening ischaemia (Rutherford classification 4-5). Eligible patients with significant atherosclerotic femoropopliteal disease (≥50% stenosis or chronic total occlusion) will be randomised in a 1:1 ratio, after successful guidewire crossing of the target lesion and confirmation of all eligibility criteria, to one of two treatment strategies: * Vessel preparation using a non-compliant plain balloon (PBA arm), followed by Legflow XP™ drug-coated balloon angioplasty. * Vessel preparation using the DKutting™ non-compliant scoring balloon (SB arm), followed by Legflow XP™ drug-coated balloon angioplasty. Vessel preparation will be performed using a 1:1 balloon-to-reference vessel diameter ratio with a minimum inflation time of 180 seconds. Predilatation with a smaller balloon will only be permitted if the allocated study balloon cannot cross the lesion. Drug-coated balloon angioplasty will subsequently be performed using the Legflow XP™ drug-coated balloon according to the study protocol. Bailout stenting will only be permitted in the presence of residual stenosis ≥30% and/or flow-limiting dissection after DCB treatment. The co-primary endpoints are bailout stenting during the index procedure and primary patency at 12 months. Secondary endpoints include freedom from clinically driven target lesion revascularisation, target limb major amputation, all-cause mortality, wound healing, health-related quality of life, procedural success, slow-flow phenomenon, procedural costs and other prespecified clinical and imaging outcomes. Duplex ultrasound follow-up examinations will undergo blinded central review by an independent duplex ultrasound core laboratory. Procedural angiographic outcomes will undergo an independent blinded quality assurance review after database lock by experienced investigators according to the prespecified study methodology. Clinical events will be adjudicated by an independent Clinical Events Committee according to prespecified endpoint definitions. Patients will be followed for 24 months after the index procedure.
Interventions
DEVICENon-compliant Plain Balloon angioplasty (PBA)
The intervention consists of preparing the artery with a non-compliant plain balloon before using the DCB (Legflow XP™; Manufacturer: Cardionovum GmbH Bonn, Germany).
DEVICENon-compliant Scoring Balloon Angioplasty (SB)
The intervention consists of preparing the artery with a non-compliant scoring balloon (DKutting™; Manufacturer: DK Medical Technology Co., Ltd., Suzhou, China) before using the DCB (Legflow XP™; Manufacturer: Cardionovum GmbH Bonn, Germany) as definitve treatment.
Sponsors
Marc Sirvent
DK Medical Technology (Suzhou) Co., Ltd.
Cardionovum GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Participants and outcome assessors will remain blinded to treatment allocation. Treating physicians and investigators responsible for the index procedure cannot be blinded because of the nature of the intervention. Duplex ultrasound follow-up examinations will undergo blinded central review by an independent core laboratory. Clinical events will be adjudicated by an independent Clinical Events Committee blinded to treatment allocation. Procedural angiographic outcomes will undergo an independent blinded quality assurance review after database lock. Statistical analyses will be performed by an independent statistician blinded to treatment allocation until completion of the primary analysis.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥18 years of age. * Rutherford class 4-5. * Estimated life expectancy \>1 year, per investigator's judgment. * Significant atherosclerotic lesions (≥50% stenosis or chronic total occlusion) in the femoropopliteal segment, including in-stent restenosis. * Signed informed consent. * Willingness to comply with follow-up visits. * ≥1 patent infragenicular artery (\<50% stenosis) at the end of the procedure. * Target vessel diameter ≤8 mm.
Exclusion criteria
* Pregnant or planning pregnancy during the study. * Participation in another drug/device trial. * Inability to cross the target lesion with a guidewire. Successful crossing is defined as advancement of the guidewire tip distal to the target lesion without vessel perforation or flow-limiting dissection. * Inadequate treatment of proximal lesion (\>30% residual stenosis). * Severe calcification of the target vessel \[group 4 of Fanelli classification17 defined as circumferential calcification (270º-360º)\], evidenced before contrast injection or digital subtraction angiography. * Thrombus in the target vessel. * Anastomotic stenosis of a bypass. * Use of atherectomy, thrombectomy, laser, or similar devices. * Prior or planned above-the-ankle amputation of the target limb. * Coagulopathy, hypercoagulable state, bleeding diathesis, platelets \<80 000/µL or \>700 000/µL, or other blood disorder. * Gastrointestinal bleeding requiring transfusion within 3 months. * Contraindication to antiplatelet/anticoagulant/thrombolytic therapy. * Acute coronary syndrome within 30 days. * Stroke or TIA within 90 days. * Hypersensitivity/contraindication to nitinol. * Comorbidities precluding treatment or follow-up (per investigator). * Hypersensitivity/allergy to contrast not manageable medically. * Hypersensitivity/allergy to heparin, aspirin, paclitaxel, clopidogrel, or other antiplatelet/anticoagulant agents. * Contraindication to dual antiplatelet therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bailout stenting | At index procedure | The need for bailout stenting during the index procedure, defined as stent implantation due to residual stenosis \>30% or a flow-limiting dissection (type C according to the Kobayashi classification) |
| Primary Patency | At 12 months | Primary patency at 12 months defined as absence of ≥50% restenosis (peak systolic velocity ratio\<2.5) and no clinically driven target lesion revascularisation (CD-TLR), as adjudicated by the duplex core laboratory and the Clinical Events Committee. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Freedom from CD-TLR | Up to 24 months post-procedure | Freedom from CD-TLR up to 24 months post-procedure. * CD-TLR is defined as any repeat revascularisation procedure performed to maintain or restore patency within the treated segment, including 5 mm proximal and 5 mm distal to the edges of the originally treated lesion, due to clinical deterioration. * Clinical deterioration is defined as a ≥1-category worsening in Rutherford classification, impaired wound healing, or new or recurrent ulceration or rest pain attributable to the target lesion |
| Change in Rutherford classification | Up to 24 months post-procedure. | Change in Rutherford classification up to 24 months post-procedure. |
| Change in EQ-5D questionnaire | Up to 24 months post-procedure | Change in EQ-5D questionnaire from baseline up to 24 months post-procedure |
| Amputation free survival | Up to 24 months post-procedure. | Amputation free survival up to 24 months post-procedure. • Amputation free survival is defined as survival without above-the-ankle amputation of the target limb. |
| Wound healing evolution | Up to 24 months post-procedure | Wound healing evolution up to 24 months post-procedure, assessed according to the following predefined ordinal classification: * Healed: Complete epithelialisation of the target wound maintained for at least 14 consecutive days. * Improved: Reduction in target wound area \>50% compared with baseline. * Unchanged: Increase or decrease in target wound area ≤50% compared with baseline. * Worsened: Increase in target wound area \>50% compared with baseline. The target wound will be defined as the largest or clinically most relevant wound identified at baseline. |
| Wound healing time | Days from the index procedure to complete epithelialisation of the target wound | Wound healing time is defined as the number of days from the index procedure to complete epithelialisation of the target wound, without drainage or need for dressing, as assessed by the treating physician. • Major amputation of the index limb or death prior to complete wound healing will be considered failure of the wound healing endpoint. |
| Device success | During the index procedure | Device success, defined as successful delivery, inflation, and retrieval of the assigned balloon catheter, resulting in a residual stenosis \<30% without flow-limiting dissection (FLD) on final angiography. |
| Technical success | During the index procedure. | Technical success, defined as successful use of a device or technique to re-establish vessel patency with a residual stenosis \<30% by visual estimation and \<50% by duplex during the index procedure. |
| Procedural cost | During the index procedure | Procedural cost, defined as the total acquisition cost (€) of all lesion preparation balloons (including adjunctive predilatation balloons, if required) and bailout stents used during the index procedure for the target lesion. |
| Slow-flow phenomenon | During the index procedure | Slow-flow phenomenon, defined as an angiographic reduction in antegrade flow occurring after DCB inflation compared with the immediately preceding angiogram, in the absence of residual stenosis \>30%, flow-limiting dissection, or vasospasm. The presence or absence of slow-flow phenomenon will be determined by the independent blinded angiographic review. |
| Procedural success | Occurring <24 hours and <1 month of the index procedure. | Procedural success, defined as technical success with absence of rupture, distal embolization, thrombosis, access complications, or major adverse cardiovascular events. These events should be listed as occurring \<24 hours and \<1 month of the procedure. |
| Freedom from Major Adverse Events (MAE) | Up to 24 months post-procedure | Freedom from Major Adverse Events (MAE) up to 24 months post-procedure. MAE are defined as the composite of: * Major Adverse Cardiovascular Events (MACE), including all-cause death, myocardial infarction, stroke, or major bleeding requiring transfusion or surgical intervention. * Major Adverse Limb Events (MALE), including above-the-ankle target limb amputation or major re-intervention involving the target lesion, defined as new bypass graft, jump/interposition graft revision, thrombectomy, thrombolysis or endovascular reintervention. |
| Freedom from device and procedure-related death | Until 30 days post-procedure | Freedom from device and procedure-related death through 30 days post-procedure. |
| Primary patency | At 6 and 24 months post-procedure | Primary patency at 6 and 24 months post-procedure, defined as absence of ≥50% restenosis (peak systolic velocity ratio\<2.5) and no CD-TLR, as adjudicated by the duplex core laboratory and the Clinical Events Committee (CEC). |
Contacts
CONTACTMarc Sirvent, PhD
Outcome results
None listed