LEVANT I 2014.

Methods	Study design: randomized controlled trial Method of randomization: sequentially numbered sealed envelopes in blocks of 4 via computer‐generated random numbers Blinding: single‐blind (participants) Exclusions postrandomization: 0 Losses to follow‐up: 5 (at 6‐month follow‐up) Study enrollment period: June 2009 to December 2009 Cross‐over: 0
Participants	Country: Europe and USA Setting: 9 hospitals Number of participants: 101 Age (mean ± SD): 67 ± 8 (DEB), 70 ± 10 (PTA) Gender: male: DEB 34 (69%), PTA 30 (58%) Rutherford class: DEB: class 2: 22%, class 3: 72%, class 4: 2%, class 5: 4%; PTA: class 2: 21%, class 3: 71%, class 4: 4%, class 5: 4% ABI (± SD): DEB: 0.69 ± 0.23, PTA: 0.60 ± 0.36 Inclusion criteria: Single de novo or (non‐instent) restenotic lesions (operator‐determined > 70% stenosis; length ≥ 4 cm and ≤ 15 cm) RVD ≥ 4 mm and ≤ 6 mm) ≥ 18 years old with Rutherford clinical category 2 to 5 Claudication or CLI Exclusion criteria: Life expectancy ≤ 2 years Creatinine > 2.5 mg/dL History of hemorrhagic stroke ≤ 3 months Previous surgery of the target lesion Previous or planned intervention ≤ 30 days Use of adjunctive therapies (including glycoprotein IIb/IlIa inhibitors) Severe lesion calcification Sudden symptom onset Acute or subacute target vessel thrombus or occlusion Absence of ≥ 1 patent untreated runoff vessel Significant inflow disease
Interventions	Uncoated balloon angioplasty: 52 (of whom 38 did not receive a stent) Uncoated balloon angioplasty device: unspecified "standard PTA balloon" DEB: 49 (of whom 37 did not receive a stent) 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 100 mg/day to 325 mg/day indefinitely and clopidogrel loading dose (75 mg or 300 mg) with maintenance for 1 month in balloon‐only participants and 3 months in stented participants Predilation before DEB: yes
Outcomes	Primary: Angiographic late lumen loss at 6 months Secondary: Device‐related adverse events Primary patency of treated segment TLR TVR Device success Successful delivery and deployment of the first inserted study device Procedural success Completion of the procedure with < 30% residual stenosis Change in ABI Change in WIQ Change in Rutherford class Serum paclitaxel levels ‐ in subsets of participants
Notes	25% of enrolled participants received a stent Clinical follow‐up at 1, 6, 12, and 24 months after the procedure Angiography of the treated limb performed at 6 months Duplex ultrasound, Rutherford classification, ABI, and WIQ evaluated at baseline, 6, 12, and 24 months Sponsor: C.R. Bard (New Hope, MN)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Subjects in each stratum (intended balloon‐only or intended stenting) were randomized 1:1 to Lutonix DCB or uncoated balloon (control group) using sequentially numbered sealed envelopes in blocks of 4 via computer‐generated random numbers"
Allocation concealment (selection bias)	Low risk	"Subjects in each stratum (intended balloon‐only or intended stenting) were randomized 1:1 to Lutonix DCB or uncoated balloon (control group) using sequentially numbered sealed envelopes in blocks of 4 via computer‐generated random numbers"
Blinding of participants and personnel (performance bias) All outcomes	High risk	The trial was "single blind" (to participant)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Primary outcome assessed by "independent, blinded angiographic core lab analysis". "Major adverse events were independently adjudicated by a Clinical events committee"
Incomplete outcome data (attrition bias) All outcomes	High risk	"Six‐month angiographic follow‐up for the primary endpoint was available for 39 patients (80%) in the Lutonix DCB group and 36 (69%) in the uncoated balloon group, due in part to 4 deaths and 5 withdrawals"
Selective reporting (reporting bias)	Low risk	All primary and secondary endpoint data reported
Other bias	High risk	8 DEB devices (16%) malfunctioned and failed to deploy properly. Antiplatelet therapy regimens varied across sites and anticoagulation protocol with heparin not specified