| Methods |
Study design: randomized controlled trial
Method of randomization: 2:1 randomization
Blinding: single‐blind (participants)
Exclusions postrandomization: 0
Losses to follow‐up: 74 of 476 participants (16%) at 12 months
Study enrollment period: July 2011 to July 2012
Cross‐over: 0 |
| Participants |
Country: Europe and USA
Setting: 54 hospitals
Number of participants: 476
Age (mean ± SD): 68 ± 10 years (DEB), 69 ± 9 years (PTA)
Gender: male: DEB 193 (61%), PTA 107 (67%)
Rutherford class: DEB: class 2: 29% class 3: 63%, class 4: 8%; PTA: class 2: 34%, class 3: 58%, class 4: 8%
ABI (± SD): DEB: 0.74 ± 0.20, PTA: 0.73 ± 0.18
Inclusion criteria:
Male or nonpregnant female aged ≥ 18 years Rutherford clinical category 2 to 4 Willing to provide informed consent, is geographically stable and comply with the required follow‐up visits, testing schedule, and medication regimen. Lesion length ≤ 15 cm Up to 2 focal lesions or segments within the designated 15 cm length of vessel may be treated (e.g. 2 discrete segments, separated by several cm, but both falling within a composite length of ≤ 15 cm) ≥ 70% stenosis by visual estimate Lesion location starts ≥ 1 cm below the common femoral bifurcation and terminates distally ≤ 2 cm below the tibial plateau AND ≥ 1 cm above the origin of the tibial plateau trunk De novo lesion(s) or nonstented restenotic lesion(s) > 90 days from prior angioplasty procedure Lesion located at least 3 cm from any stent, if target vessel was previously stented Target vessel diameter between ≥ 4 mm and ≤ 6 mm and able to be treated with available device size matrix Successful, uncomplicated (without use of a crossing device) antegrade wire crossing of lesion A patent inflow artery free from significant lesion (≥ 50% stenosis) as confirmed by angiography (treatment of target lesion acceptable after successful treatment of inflow artery lesions) At least 1 patent native outflow artery to the ankle, free from significant (≥ 50%) stenosis as confirmed by angiography that has not previously been revascularized (treatment of outflow disease is NOT permitted during the index procedure) Contralateral limb lesion(s) cannot be treated within 2 weeks before or planned 30 days after the protocol treatment (or both) in order to avoid confounding complications No other prior vascular interventions within 2 weeks before or planned 30 days after the protocol treatment (or both)
Exclusion criteria:
Pregnant or planning on becoming pregnant or men intending to father children Life expectancy < 5 years Currently participating in an investigational drug or other device study or previously enrolled in this study History of hemorrhagic stroke within 3 months Previous or planned surgical or intervention procedure within 2 weeks before or within 30 days after the index procedure History of MI, thrombolysis, or angina within 2 weeks of enrolment Rutherford class 0, 1, 5, or 6 Renal failure or chronic kidney disease with MDRD glomerular filtration rate ≤ 30 mL/minute/1.73 m2 (or serum creatinine ≥ 2.5 mg/L within 30 days of index procedure or treated with dialysis) Prior vascular surgery of the index limb, with the exception of remote common femoral patch angioplasty separated by at least 2 cm from the target lesion Inability to take required study medications or allergy to contrast that cannot be adequately managed with pre‐ and postprocedure medication Anticipated use of class IIb/IIIa inhibitor prior to randomization Ipsilateral retrograde access Composite lesion length > 15 cm or no normal proximal arterial segment in which duplex flow velocity could be measured Significant inflow disease. Successful treatment of inflow disease allowed prior to target lesion treatment Known inadequate distal outflow (> 50% stenosis of distal popliteal or all 3 tibial vessels, or both), or planned future treatment of vascular disease distal to the target lesion Sudden symptom onset, acute vessel occlusion, or acute or subacute thrombus in target vessel Severe calcification that renders the lesion undilatable Use of adjunctive primary treatment modalities (i.e. laser, atherectomy, cryoplasty, scoring/cutting balloon, etc.)
|
| Interventions |
Uncoated balloon angioplasty: 160
Uncoated balloon angioplasty device: unspecified "standard PTA balloon"
DEB: 316
DEB device: Lutonix DEB (C.R. Bard, New Hope, MN)
Drug used: paclitaxel 2 μg/mm2 balloon surface
Vessels treated: femoropopliteal arteries
Anticoagulation/platelets: according to local clinical practice
ASA loading dose 75 mg to 325 mg before the procedure and 75 mg/day to 100 mg/day indefinitely, and clopidogrel or prasugrel loading dose (clopidogrel 75 mg or 300 mg and prasugrel 10 mg or 60 mg) before the procedure and clopidogrel 75 mg/day or prasugrel 5 mg to 10 mg (depending on bodyweight) for at least 1 month postoperatively
Predilation before DEB: yes |
| Outcomes |
Primary:
Primary effectiveness measure: primary patency of the target lesion at 12 months Primary safety measure: composite of freedom from perioperative death from any cause (≤ 30 days after the procedure) and freedom at 12 months from index‐limb amputation, index limb revascularization, and index‐limb‐related death (i.e. death from a medical complication related to a limb)
Secondary:
Procedural success Clinically driven TLR Changes from baseline in the Rutherford classification WIQ scores QoL measures (the EQ‐5D and SF‐36 scores) All‐cause mortality rate Amputation‐free survival TVR Reintervention for thrombosis
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| Notes |
Primary patency defined as the absence of evidence of binary restenosis and freedom from TLR
Procedural success defined as technical success without periprocedural complications
Participants were followed up at 1, 3, and 12 months postoperatively
Sponsor: C.R. Bard (New Hope, MN) |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
Participants were randomized 2:1 to the intervention and control arms, but the methodology of randomization not explained in the manuscript, supplementary materials, or study protocol |
| Allocation concealment (selection bias) |
Unclear risk |
Methodology of allocation not explained in the manuscript, supplementary materials, or study protocol |
| Blinding of participants and personnel (performance bias)
All outcomes |
High risk |
"The clinician was aware of the index treatment because the drug‐coated balloon looked different from a standard balloon" |
| Blinding of outcome assessment (detection bias)
All outcomes |
Low risk |
"Investigators who completed follow‐up, vascular‐laboratory personnel, core laboratory evaluators, and members of the clinical‐events committee were unaware of the treatment received" |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
Only 16% of participants were lost to follow‐up over the 12‐month study period |
| Selective reporting (reporting bias) |
Low risk |
All primary and secondary endpoint data reported |
| Other bias |
Low risk |
Participants randomized after a lesion was predilated so people requiring stent placement were excluded. More challenging or dissection‐prone lesions were thus excluded from this study, which may not be reflective of existing clinical practices |
