Spreen 2016.

Methods	Country: The Netherlands Setting: 3 major vascular centres in the Netherlands Study design: multi‐centre RCT Level of randomisation: participant
Participants	No. of participants randomised: A total of 144 limbs in 137 patients with critical limb ischaemia were randomised to angioplasty (69 limbs in 67 participants) or primary stenting (75 limbs in 74 participants) (4 participants included for 2 limbs, with 1 limb in each arm) Exclusions post randomisation: 3 participants (3 limbs) in the PTA group did not receive intervention; reasons: intermittent claudication, renal failure without dialysis, and coagulation disorder. One participant (1 limb) in the stent group did not receive intervention; reason: vessel too small. Overall, 64 participants (66 limbs) received the allocated PTA intervention, and 73 participants (74 limbs) received the allocated stent treatment Shifted to another arm: none Age (mean), years: PTA group 73, stent group 74 Gender: PTA group 47 male/17 female, stent group 49 male/24 female Gender: PTA group: 14 male/8 female, stent group 6 male/10 female Inclusion criteria: age > 18 years; if female patient with child‐bearing potential, may not be pregnant at study entry and must utilise reliable birth control for the duration of participation in the study; must be willing and able to comply with the specified follow‐up evaluation; critical limb ischaemia, defined as Rutherford category 4 (ischaemic rest pain), 5 (minor tissue loss), or 6 (major tissue loss); stenosis (> 50% luminal loss) or occlusion of an infrapopliteal artery, including the tibiofibular trunk, the anterior tibial artery, the posterior tibial artery, and the fibular artery; target lesion length ≤ 90 mm; artery to be treated with diameter ≥ 2 mm and ≤ 6 mm; patent common iliac, external iliac, superficial femoral, and popliteal artery on the ipsilateral side before randomisation, possibly after treatment during the same session. At least 1 patent crural (anterior tibial, posterior tibial, or fibular) artery with expected unobstructed runoff to ankle level after treatment Exclusion criteria: acute limb ischaemia; previous amputation of affected limb at or above ankle level; subacute limb ischaemia, which requires thrombolysis as first treatment modality; active bleeding or bleeding diathesis; recent (≤ 3 months) haemorrhagic stroke or any other CNS abnormality with increased risk of haemorrhage, such as intracranial neoplasm, arteriovenous malformation, intracranial aneurysm, or aneurysm repair; gastrointestinal or genitourinary bleeding of clinical significance within the previous 6 weeks before treatment; aneurysm in common femoral, superficial femoral, or popliteal artery on the ipsilateral side; surgical revascularisation involving the same limb within 30 days before the index procedure or planned surgical revascularisation of the same limb within 30 days of the index procedure; previous implanted stent at the index site; life expectancy < 6 months or other factors making clinical follow‐up difficult; known allergy to acetylsalicylic acid (aspirin), clopidogrel, heparin, or paclitaxel; known allergy to contrast media; known heparin‐induced thrombocytopaenia (HIT type 2); unable or unwilling to tolerate anticoagulant, antiplatelet therapy, or contrast media; creatinine clearance 20 mL/min (as derived from Cockcroft‐Gault formula); severely calcified lesions with expected resistance to stenting; poor inflow due to ipsilateral stenosis or occlusions of the iliac or femoropopliteal arteries that cannot be treated during the same session; significant vessel tortuosity or other parameters prohibiting access to the lesions and/or delivery of the stent; without (expected) distal runoff to the index site
Interventions	Stenting group: In the treatment arm, target lesions were treated with balloon expandable paclitaxel‐eluting stainless steel stents (TAXUS Liberté; Boston Scientific, Natick, MA, USA). If necessary, according to the operator, mainly in cases of occlusion, lesions were pre‐dilated. The full length of lesions was covered, and when necessary, overlapping stents were deployed (maximum 3 stents allowed) PTA group (control): A balloon with diameter matching the target vessel was advanced over the guidewire and was inflated at the target lesion site. If bailout stenting was required (secondary to post‐PTA occlusion or flow‐limiting dissection), only non‐drug‐eluting bare‐metal stents were allowed Medication: During the procedure, 5000 international units of heparin was administered intra‐arterially Post procedure, all participants were prescribed 100 mg carbasalate calcium daily indefinitely and 75 mg clopidogrel daily (with 300‐mg loading dose) orally for ≥6 months
Outcomes	Primary outcome: Patency per treated lesion at months, defined as ≤ 50% loss of luminal diameter without re‐intervention in the interim. If CTA was not available but digital subtraction angiography or duplex sonography was available, patency of treated sites was scored by those techniques Secondary outcomes: Ischaemic categorisation of the treated leg by means of Rutherford classification (at 6 months and 12 months), minor and major amputation (at or below vs above ankle level, respectively) of the trial leg (at 6 months and 12 months), periprocedural (within 30 days) complications, serious adverse events, death
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random sequence on a 1:1 basis. Randomisation per limb and stratified in blocks per centre. Block size (n = 4) known only to the statistician
Allocation concealment (selection bias)	Low risk	Sealed and opaque envelope
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants, operators, and investigators not blinded to treatment assignment
Blinding of outcome assessment (detection bias) All outcomes	High risk	Not mentioned
Incomplete outcome data (attrition bias) All outcomes	Low risk	All data accounted for. ITT analysis reported
Selective reporting (reporting bias)	Low risk	None
Other bias	Unclear risk	One study author has received speakers’ fees from Cordis Corporation, Fremont, CA, USA; Cook Medical, Bloomington, IN, USA; and AngioDynamics, Latham, NY, USA