IN.PACT SFA 2015.

Methods	Study design: randomized controlled trial Method of randomization: participants were randomly assigned by an Interactive Voice Response System with the use of a method of permuted blocks to ensure that a 2:1 ratio was maintained across sites Blinding: single‐blinded Exclusions postrandomization: DEB: 13 participants, PTA: 4 participants Losses to follow‐up: DEB: 3 participants, PTA: 3 participants Study enrollment period: September 2010 to April 2011 and April 2012 to January 2013 Cross‐over: 0 The trial included 2 cohorts: European (IN.PACT SFA I) and North American (IN.PACT SFA II)
Participants	Country: Europe, USA, and Canada Setting: hospital (13 sites in Europe, 44 in the USA and Canada) Number of participants: 331 Age (mean ± SD): 67.5 ± 9.5 years (DEB), 68.0 ± 9.2 years (PTA) Gender: males: DEB 65%, PTA: 67.6% Rutherford class: DEB: class 2: 37.7%, class 3: 57.3%, class 4: 5%, class 5: 0%; PTA: class 2: 37.8%, class 3: 55.9%, class 4: 5.4%, class 5: 0.9% ABI: DEB: 0.769 ± 0.228, PTA: 0.744 ± 0.189 Inclusion criteria: Moderate to severe intermittent claudication or ischemic rest pain (Rutherford class 2 to 4) and stenosis of 70% to 99% with lesion lengths between 4 and 18 cm or occlusion with lengths of ≤ 10 cm involving the superficial femoral and proximal popliteal arteries Exclusion criteria: Unwilling or unlikely to comply with follow‐up schedule Stroke or STEMI within 3 months prior to enrolment Acute or subacute thrombus in the target vessel
Interventions	Uncoated balloon angioplasty: 111 Uncoated balloon angioplasty device: unspecified "standard PTA balloon" DEB: 220 DEB device: IN.PACT Admiral (Medtronic, Santa Rosa, CA) Drug used: paclitaxel 3.5 μg/mm2 balloon surface Vessels treated: femoropopliteal arteries Anticoagulation/platelets: periprocedural: loading dose of ASA 300 mg to 325 mg and clopidogrel 300 mg within 24 hours of the index procedure or 2 hours postprocedure. Heparin administered at the time of the procedure to maintain an activated clotting time ≥ 250 seconds Postprocedural: ASA 81 mg/day to 325 mg/day (for a minimum of 6 months) and clopidogrel 75 mg/day for a minimum duration of 1 month for nonstented participants and 3 months for participants who received stents Predilation before DEB: yes
Outcomes	Primary: Primary patency at 12 months following the index procedure (defined as freedom from clinically driven TLV and restenosis (defined as peak velocity ratio ≤ 2.4) Secondary: 30‐day device‐ and procedure‐related mortality All‐cause mortality Major target limb amputation Target vessel thrombosis Acute procedural success TVR at 12 months Primary sustained clinical improvement (defined as freedom from target limb amputation, TVR, and increase in Rutherford class at 12 months) QoL outcomes (using the EQ‐5D and the WIQ)
Notes	Primary patency defined as freedom from clinically driven TLV and restenosis as determined by a duplex ultrasonography‐derived peak systolic velocity ratio of ≤ 2.4 Participants were followed by the treating physician at 30 days, 6 months, and 12 months, including office visits with duplex ultrasonography functional testing and adverse event assessment Sponsor: Medtronic, Santa Rosa, CA
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Subjects were randomly assigned by an Interactive Voice Response System with the use of a method of permuted blocks to ensure that a 2:1 ratio was maintained across sites"
Allocation concealment (selection bias)	Low risk	"Subjects were randomly assigned by an Interactive Voice Response System with the use of a method of permuted blocks to ensure that a 2:1 ratio was maintained across sites"
Blinding of participants and personnel (performance bias) All outcomes	High risk	"Because of the visual difference between the IN.PACT DCB and standard PTA balloon, treating physicians, research coordinators, and catheterization laboratory staff were not blinded to the treatment assignment
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"Independent core laboratories analyzed all images, including duplex ultrasonography", "Each component of the primary efficacy end point was independently adjudicated by the blinded Clinical Events Committee"
Incomplete outcome data (attrition bias) All outcomes	Low risk	94% of DEB participants and 96% of PTA participants analyzed at 1 year. "Multiple imputation was performed by using the logistic regression approach for patients with missing primary end point data (29 DCB, 7 PTA)"
Selective reporting (reporting bias)	Low risk	Restenosis rate not reported. While this omission was concerning, the remaining outcomes were reported and as such this single omission does not, in our opinion, place the study at a high risk of reporting bias
Other bias	Unclear risk	The outcomes of the 9% of stented participants were not reported. However, the authors stated that, "when stented patients were excluded from the analysis, there were no changes in any of the conclusions". The majority of study authors declared a financial relationship with the study sponsor