Brodmann 2011.

Methods	Country: Austria Setting: monocentre university hospital Study design: RCT Level of randomisation: participant
Participants	No. of participants randomised: 54 patients were randomised to primary stenting (balloon expandable stent) or PTA alone Exclusions post randomisation: not mentioned; assumed none Shifted to another arm: 2 participants in PTA group with dissection in treated vessels required secondary stent, and total of 3 stents were placed Number of participants evaluated: overall 54 participants were included, with 33 assigned to the PTA group and 21 to the stent group Age (mean), years: 74.9 PTA, 68.9 stent Gender: 13/33 males PTA, 12/21 males stent Inclusion criteria: critical limb ischaemia, with Rutherford classification 4 to 6; lesion criteria characterised as the following: isolated stenoses > 70%, sequential stenoses up to cumulative length 12 cm, or total occlusion of crural arteries with maximum length 12 cm; target vessel must be a distal runoff vessel; written informed consent; life expectancy ≥ 12 months Exclusion criteria: endovascular procedure at the target vessel within the last 3 months; refused informed consent; known allergy against clopidogrel or aspirin; indication for oral anticoagulation (atrial fibrillation); concomitant participation in another clinical trial. Lesions in the inflow arteries needing to be treated were submitted to standardised treatment of femoropopliteal arteries
Interventions	For all patients eligible for the trial, antegrade access was chosen. After a 6 F sheath (Brite Tip, Cordis, Johnson & Johnson, New Brunswick, NJ, USA) was introduced, a diagnostic angiogram was obtained. 3000 units of unfractionated heparin was administered The target lesion in the infrapopliteal arteries was selected, and in case of successful passage of the target lesion with a hydrophilic‐coated guidewire (Standard Glide Wire, 0.035 inch, Terumo Medical Corporation, Somerset, NJ, USA; V‐18, Control™ Wire, Boston Scientific, Marlborough, MA, USA; or Hi‐Torque Sparta Core 14 Guide Wire, Abbott Vascular, Abbott Park, IL, USA) and the help of a support catheter, the randomisation process was done as described above If the lesion could not be passed with a guidewire, the patient was not included. To secure standardised documentation of the target lesion, a measuring tape was applied, leading down from the popliteal fossa to the foot of the patient. Before and after the procedure, angiography was performed in 2 planes, with a difference in angle of at least 30 degrees. In case of lesions in the inflow arteries, these were treated before the revascularisation procedure of the infrapopliteal arteries was performed PTA group: The procedure was performed with the Amphirion Deep catheter (Invatec S.r.l., Roncadelli (Bs), Italy) Stenting group: Primary stent placement was performed with a balloon expandable stent with a silicon‐carbide coating ‐ the Motion Explorer Stent (Biotronik, GmbH&Co. KG, Berlin, Germany). Stents with a diameter of 2.5 mm up to 3.5 mm and a length of 15 mm up to 25 mm were used. The lesion was exactly calculated using a programme for measurements. A 0.014‐inch guidewire (HI Torque, Sparta Cor 14, Guidant Corporation, Santa Clara, CA, USA) was used for PTA and stenting procedures Medication: The evening before the procedure, the participant received 300 mg clopidogrel; after the procedure, all participants were treated with low‐molecular‐weight heparin (enoxaparin 40 mg twice daily) for 48 hours Immediately after the procedure, the participant was put on a dual platelet aggregation therapy, with aspirin 100 mg a day and clopidogrel 75 mg a day for 3 months 3 months post procedure, participants were put on aspirin 100 mg a day as long‐term prophylactic therapy
Outcomes	The main study endpoint was 1‐year clinical benefit, defined by improvement of at least 1 Rutherford category compared to baseline Quote: "Follow‐up examinations for all patients in the trial were performed the day aft er the successful procedure, at month 3, 6 and 12 thereafter. At each date a clinical evaluation referring to the Rutherford classification was done. In case of Rutherford classification 5 – 6 the wound was measured geometrically and compared in size to the prior visits. For rest pain evaluation, a standardised pain scale (NRS, numeric rating scale) was used. Walking distance was evaluated by treadmill testing. Ankle brachial index (ABI) and colour coded duplex sonography of the target lesion were done at each visit. The target lesion was targeted by duplex sonography referring to the measurement during the intervention. A measuring tape was once again applied leading down from the popliteal fossa to the foot of the patient to refind the formerly treated lesion. Colour coded duplex sonography was performed by two experienced study technicians and included an evaluation of the whole artery treated. The definition of 70% re‐stenosis was based on a proximal PVR > 3,4 calculated on duplex ultrasound. PVR was defined as peak systolic flow velocity in the lesion divided by the peak systolic flow velocity ˜1 cm proximal to the lesion. If a relevant re‐obstruction was suspected digital subtraction angiography (DSA) was performed, and at month 12 all patients underwent magnetic angiography (MRA). In all patients at each time of evaluation concomitant medication and medical events (especially cardiovascular events) were taken" Secondary endpoints were 3‐month and 6‐month primary patency rate; 3‐, 6‐, and 12‐month secondary patency; and 12‐month target lesion revascularisation rate The second primary endpoint was 12‐month primary patency, defined as freedom from re‐stenosis > 70% detected with duplex ultrasound Quote: "The definition of 70% restenosis was based on a proximal PVR > 3,4 calculated on duplex ultrasound. PVR was defined as peak systolic flow velocity in the lesion divided by the peak systolic flow velocity ˜1 cm proximal the lesion" Major adverse events were any amputation, the need for acute surgical revascularisation, and death related to the procedure
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The randomisation process was conducted with a computer‐generated list (blocked randomisation)"
Allocation concealment (selection bias)	Low risk	Quote: "The patients were listed for primary stent implantation or PTA alone with the usage of sequential numerated closed envelopes, which contained information about the planned procedure" Quote: "The blinding was warranted due to sealed envelopes and randomisation was done in the catheter lab immediately after successful passing of the target lesion with the guide wire. The randomisation was performed per patient"
Blinding of participants and personnel (performance bias) All outcomes	High risk	None
Blinding of outcome assessment (detection bias) All outcomes	High risk	Not mentioned
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "The whole follow up period of 12 months was completed by 44 patients. 9 patients (16.7%) had died, 8 due to cardiovascular death, one had developed lung cancer. One patient refused to show up for the follow up visits after 3 months" No ITT analysis was performed
Selective reporting (reporting bias)	Low risk	None
Other bias	High risk	Quote: "Originally the trial was planned as a multicenter trial with the appropriate randomisation therefore, but at the end it was performed as a monocentric study, because the other participating centers had difficulties including appropriate patients. They did not include any patient over the whole study period. This explains the different numbers of patients in the two treatment groups" Quote: "At baseline evaluation all cardiovascular risk factors were more pronounced in the stent group than in the PTA group, with the biggest and statistically significant difference in hyperlipidemia in spite of lipidemic treatment (n = 14 (66.7%) versus 6 (18.2%); P < 0.0001). For diabetes mellitus, concerning the fact of insulin therapy there was a difference between the stent and PTA group, too (47.6% versus 36.4%)"