THUNDER 2008.

Methods	Study design: randomized controlled trial Method of randomization: participants were assigned to different treatment groups according to a lot‐generated random list Blinding: participant blinded Exclusions postrandomization: 0 Losses to follow‐up: 3 Study enrollment period: June 2004 to June 2005 Cross‐over: 0
Participants	Country: Germany Setting: 3 hospitals Number of participants: 154 Age (mean ± SD): 69 ± 8 years (DEB), 68 ± 9 years (PTA) Gender: males: DEB 31 (65%), PTA 34 (63%) Rutherford class (mean ± SD): DEB: 3.4 ± 0.8, PTA 3.1 ± 0.8 ABI (± SD): DEB: 0.5 ± 0.3, PTA 0.5 ± 0.3 Inclusion criteria: Age 18 to 95 years Rutherford class 1 to 5 ≥ 1 obstructive lesions or new lesions or restenoses ≥ 70% of vessel diameter and ≥ 2 cm in length, in the SFA, the popliteal artery, or both Exclusion criteria: Poor inflow Absence of a patent crural artery Acute onset of symptoms Pregnancy Life expectancy < 1 year Contraindications to required medications
Interventions	Uncoated balloon angioplasty: 54 Uncoated balloon angioplasty device: Bavaria Medizintechnologie DEB: 48 DEB device: Bavaria Medizintechnologie Drug used: paclitaxel 3 μg/mm2 balloon surface, mean dose (± SD) 4.7 ± 3.μg Vessels treated: femoropopliteal arteries Anticoagulation/platelets: participants not already taking ASA and clopidogrel were administered loading doses of 300 mg of each drug 12 hours before the procedure. All participants received ASA 100 mg/day indefinitely and clopidogrel 75 mg/day for 4 weeks after the intervention. In addition, participants were given an intra‐arterial bolus of heparin 3000 U to 5000 U) at the time of the procedure Predilation before DEB: yes
Outcomes	Primary: Late lumen loss at 6 months Secondary: The secondary efficacy endpoints were the technical success of the intervention 6‐month angiographic restenosis rate (i.e. incidence of stenosis of ≥ 50% of the diameter of the reference‐vessel segment) Change in Rutherford class ABI Patency rate Incidence of TLR
Notes	Study had 3 arms: balloons coated with paclitaxel, uncoated balloons with paclitaxel dissolved in the contrast medium, and uncoated balloons Clinical evaluations were performed at baseline, at 24 to 72 hours after intervention, and at 6 months after intervention Angiographic evaluation of restenosis was performed at 6 months with the same projections as those used during intervention Sponsor: Bavaria Medizintechnologie and Schering, Germany
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were assigned to different treatment groups according to a lot‐generated random list
Allocation concealment (selection bias)	Unclear risk	No mention of allocation concealment strategy
Blinding of participants and personnel (performance bias) All outcomes	High risk	The paclitaxel‐coated balloons had a distinctive appearance that could be recognized by the investigators, who also performed some of the poststudy evaluations
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	"The paclitaxel‐coated balloons had a distinctive appearance that could be recognized by the investigators, who also performed some of the poststudy evaluations". "All angiograms were assessed in a blinded fashion by an independent angiographic core laboratory (C2RM, Lille, France)"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Only 2 DEB participants and 1 PTA participant did not undergo clinical follow‐up and angiography at 6 months
Selective reporting (reporting bias)	Low risk	All primary and secondary endpoint data reported
Other bias	High risk	4% of the intervention and 22% of control participants were stented but little discussion was provided of the outcomes in those participants

ABI: ankle‐brachial index; ASA: acetylsalicylic acid (aspirin); BTHC: n‐butyryl tri‐nhexyl citrate; BTK: below the knee; CLI: critical limb ischemia; DCB: drug‐coated balloon; DEB: drug‐eluting balloon; DES: drug‐eluting stent; DS: diameter stenosis; EQ‐5D: Euro‐Qol Group 5‐Dimension Self‐Report Questionnaire; IU: international unit; MAE: major adverse events; MDRD: modification of diet in renal disease; MI: myocardial infarction; MLD: minimum lumen diameter; PTA: percutaneous transluminal angioplasty; QoL: quality of life; QVA: quantitative vascular angiography; RVD: reference vessel diameter; SD: standard deviation; SFA: superficial femoral artery; SF‐36: Medical Outcomes Study 36‐Item Short‐Form Health Survey; TASC: Trans‐Atlantic Inter‐Society Consensus Document on Management of Peripheral Arterial Disease; TLR: target lesion revascularization; TVR: target vessel revascularization; U: unit; WIQ: Walking Impairment Questionnaire.