BIOLUX P‐I.

Methods	Study design: randomized controlled trial Method of randomization: computer‐generated randomization lists Blinding: participants were blinded but the operators were not blinded Exclusions postrandomization: none Losses to follow‐up: 5 Study enrollment period: October 2010 to August 2011 Cross‐over: 0
Participants	Country: Austria and Germany Setting: 4 German hospitals and 1 Austrian hospital Number of participants: 60 (68 lesions) Age (mean ± SD): 71 ± 10 years Gender: male 57% Rutherford class: DEB: class 2: 23.3%, class 3: 56.7%, class 4: 13.3%, class 5: 6.7%; PTA: class 2: 30%, class 3: 56.7%, class 4: 6.7%, class 5: 6.7% ABI (± SD): 0.7 ± 0.2 Inclusion criteria: Age ≥ 50 years Informed consent signed by participant prior to randomization Single or sequential de novo or re‐stenotic lesions (stenosis ≥ 70% diameter reduction or occlusion) in the femoropopliteal arteries ≥ 30 mm and ≤ 200 mm long Rutherford class 2 to 5 in the target limb RVD 3 mm to 7 mm, based on visual estimation Inflow free from flow‐limiting lesion (< 50% stenosis) confirmed by angiography. People with flow‐limiting inflow lesions (> 50% stenosis) could be included if lesion had been treated successfully before the index procedure At least 1 nonoccluded crural vessel (e.g. without significant stenosis) with angiographically documented runoff to the foot Successful wire crossing of the lesion Willingness to comply with all specified follow‐up evaluations Male or negative pregnancy test of women in childbearing age Exclusion criteria: Comorbid conditions limiting life expectancy ≤ 1 year People currently participating in another clinical trial Lesions that were untreatable with PTA or other intervention techniques The target stenosis located distal to a stenosis ≥ 50% that could not be pretreated because the drug coating could get lost during crossing the proximal lesion Thrombus in the target vessel, documented by angiography Target lesion severely calcified, documented by angiography Prior bypass surgery of target vessel Previously implanted stent in the target lesion Treatment of bifurcation required Planned amputation of the target limb Flow‐limiting (> 50% DS) inflow lesion proximal to target lesion, left untreated Failure to obtain < 30% residual stenosis in a pre‐existing hemodynamically significant (> 50% DS) inflow lesion in the ipsilateral iliac or proximal SFA (DEB or DES not allowed for the treatment of inflow lesion) Additional hemodynamically relevant proximal and distal lesions with stenosis ≥ 50%, except iliac arteries, excluded. Iliac artery lesion treatments had to be successful with a residual stenosis ≤ 30% Hemorrhagic diathesis or another disorder such as gastrointestinal ulceration or cerebral circulatory disorders that restricted the use of platelet aggregation inhibitor therapy and anticoagulation therapy Phenprocoumon intake Impaired renal function (creatinine ≥ 2.0 mg/dL to 2.5 mg/dL), according to investigator assessment Known allergy to contrast media that could not be adequately controlled with premedication Allergy, intolerance or hypersensitivity to paclitaxel structurally or related compounds or to the delivery matrix BTHC, or both
Interventions	Uncoated balloon angioplasty: 30 participants, 35 lesions Uncoated balloon angioplasty device: Passeo‐18 PTA catheter DEB: 30 participants, 33 lesions DEB device: Passeo‐18 Lux drug‐releasing balloon catheter Drug used: paclitaxel 3 μg/mm2 balloon surface Vessels treated: femoropopliteal arteries Anticoagulation/platelets: dual antiplatelet therapy recommended for 1 month postprocedure and for 3 months in case of bailout stenting with a bare metal stent Predilation before DEB: yes: 66.7% of DEB and 30% of PTA procedures
Outcomes	Primary: Late lumen loss, assessed by QVA analysis Secondary: Binary restenosis rate, defined as a diameter reduction > 50% at the time of follow‐up TLR rate Change in mean ABI Change in Rutherford classification MAE rate (procedure‐ or device‐related death or amputation, target lesion thrombosis and clinically driven TLV)
Notes	Clinical and angiographic follow‐up was scheduled at 6 months ± 30 days and clinical follow‐up at 12 months ± 30 days 6% of participants were treated in the anterior and posterior tibial arteries Sponsor: Biotronik AG
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization lists were computer generated"
Allocation concealment (selection bias)	Low risk	"Sealed envelopes with the randomization group included were provided to the sites"
Blinding of participants and personnel (performance bias) All outcomes	High risk	"The operators could not be blinded to the assigned treatment, which might have affected the rate of predilation and bailout stenting"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"QVA analysis was performed by an independent core laboratory (MedStar Health Research Institute, Washington, DC, USA), and the study was supervised by an independent clinical events committee and data safety monitoring board"
Incomplete outcome data (attrition bias) All outcomes	High risk	"Follow‐up compliance was low, with 4 subjects withdrawing consent and 5 patients lost to follow‐up"
Selective reporting (reporting bias)	Low risk	The authors reported all prespecified outcomes
Other bias	High risk	Predilation was performed more often in people receiving DEB than PTA (66.7% with DEB vs. 30% with PTA, P = 0.010), and technical success was higher in the DEB group (76.7% with DEB vs. 46.7% with PTA, P = 0.017). 26.7% of the control arm required bailout stenting. Most of the people receiving DEB (56.7%) and PTA (60%) had a history of previous peripheral interventions, although the type and location of those interventions was not specified