PACIFIER 2012.

Methods	Study design: randomized controlled trial Method of randomization: computer generated, in blocks of 10 participants Blinding: single‐blind (participants) Exclusions postrandomization: 0 Losses to follow‐up: 4 participants at 6 months, 10 participants at 12 months Study enrollment period: 2010 to 2011 Cross‐over: 0
Participants	Country: Germany Setting: hospital (3 centers) Number of participants: 85 (91 intervention procedures, 1 target lesion per procedure) Age (mean ± SD): 71 ± 7 years (DEB), 71 ± 9 years (PTA) Gender: males: DEB 26 (59%), PTA 30 (64%) Rutherford class: DEB: class 2: 9.1%, class 3: 86.4%, class 4: 0%, class 5: 4.5%; PTA: class 2: 12.8%, class 3: 83%, class 4: 4.3%, class 5: 0% ABI: DEB: 0.73 ± 0.30, PTA: 0.65 ± 0.26 Inclusion criteria: Claudication or CLI (Rutherford class 2, 3, 4, or 5) Atherosclerotic disease involving the SFA or the popliteal artery Lesion length 3 cm to 30 cm An occlusion or a grade of stenosis ≥ 70% Absence of contraindications to dual antiplatelet therapy Written informed consent Exclusion criteria: Acute thrombus or aneurysm in the target vessel Failure to cross the target lesion with a guidewire Inflow lesions that could not be successfully pretreated Significant disease of all 3 infrapopliteal vessels Renal failure (serum creatinine > 2.0 mg/dL) Known intolerance or allergy to study medications Life expectancy < 2 years
Interventions	Uncoated balloon angioplasty: 47 procedures in 44 participants Uncoated balloon angioplasty device: Pacific Xtreme (Medtronic, Santa Rosa, CA) DEB: 44 procedures in 41 participants DEB device: IN.PACT Pacific (Medtronic, Santa Rosa, CA) Drug used: paclitaxel 3 μg/mm2 balloon surface Vessels treated: femoropopliteal arteries Anticoagulation/platelets: all participants were pretreated with ASA and thienopyridines, which were continued for > 2 months after PTA Predilation before DEB: yes: DEB 6 cases (13.6%), PTA 3 cases (6.4%)
Outcomes	Primary: Late lumen loss at 6 months Secondary: Binary restenosis at 6 months Rutherford class change at 6 months TLR at 6 and 12 months Major adverse clinical events (death, target limb amputation, or TLV) at 6 and 12 months
Notes	Follow‐up to 24 months reported Stents provisionally implanted in 9 (20.5%) DEB cases and 16 (34%) PTA cases Sponsor: Medtronic (Santa Rosa, CA)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"The randomization sequence was computer generated, in blocks of 10 patients each"
Allocation concealment (selection bias)	Low risk	"Allocation concealment was guaranteed by the use of numbered, opaque, sealed envelopes, which were only opened after the decision was made that the patient had to be treated according to the protocol"
Blinding of participants and personnel (performance bias) All outcomes	High risk	"Blinding of investigators after assignment of a patient to a treatment is not possible due to differences in the appearance of coated and uncoated catheters"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Primary endpoint "assessed by blinded angiographic core lab quantitative analyses"
Incomplete outcome data (attrition bias) All outcomes	High risk	Missing primary outcome data on 20.5% of DEB arm and 27.3% of control arm
Selective reporting (reporting bias)	Low risk	All primary and secondary endpoint data reported
Other bias	High risk	21% of DEB and 34% of control participants were stented but little discussion of outcomes in those participants. Baseline risk characteristics such as smoking and diabetes were unevenly distributed between DEB and control arms. Dosing and duration of antiplatelet therapies were unclear