Zhang 2012.

Study characteristics
Methods	Study design: prospective, multicentre, randomised, double‐blind study Method of randomisation: not mentioned Blinding: participants ‐ yes, doctor‐ yes, outcome assessors ‐ yes Power calculation: not mentioned Total number of participants: 288, 216 to receive POL (72 patients in each group) and 72 patients to receive placebo Total number of procedure: 288 Treatment localisation: leg veins Number of exclusions post‐randomisation: none Number of withdrawals and reasons: "Two patients assigned to polidocanol 1% and one patient assigned to placebo did not receive any study medication and were therefore excluded from the safety population (n = 285)."
Participants	Setting: outpatient site Country: China Gender: men and women Age: range 18 ‐ 75 years Inclusion criteria: C1 or C2 non‐saphenous varicose veins of the lower legs and a normal deep venous system; given informed consent Exclusion criteria: history of DVT or high risk of thrombosis; arterial occlusive disease; thromboembolic diseases; acute severe systemic diseases or very poor general health; known hypercoagulability or current anticoagulation therapy; major leg oedema; febrile states; symptoms of microangiopathy or neuropathy or inflammatory skin disease in the treatment area; or predisposition to allergies
Interventions	Treatment Group A: C1 spider veins of < 1 mm; treatment: POL 0.5% or corresponding placebo (same solution but without the active ingredient) Treatment Group B: C1 reticular veins and/or small‐sized veins of 1 mm – 5 mm; treatment: POL 1% or corresponding placebo Treatment Group C: C2 medium‐sized and/or large non‐saphenous subcutaneous varicose veins of > 5 mm with reflux of 0.5 second; treatment: POL 3% or corresponding placebo Duration of follow‐up: 3 months Use of compression: compression stocking
Outcomes	Primary efficacy variable: efficacy of the study treatment at 3 months after the last injection The efficacy of the treatment was rated according to the following 5‐grade scale: 1 ‘worse than before’ (more veins in the treatment area are observable than before or veins are more dilated or look worse than before), 0% disappearance but worsening; 2 ‘same as before’ (no improvement but also no worsening observable), from 0% up to 25% disappearance; 3 ‘moderate improvement (improvement observable but not yet satisfactory, needs to be treated again, from 26% up to 50% disappearance; 4 ‘good improvement (satisfactory treatment success, only slight improvement still possible), from 51% up to 75% disappearance; 5 ‘complete treatment success' (no improvement necessary), ≥ 75% disappearance. Patients who had Grade 4 or 5 were counted as responders Secondary efficacy variables: investigators' and patients' assessments of treatment satisfaction at the final examination according to a 5‐point verbal rating scale: 1 very unsatisfied; 2 somewhat unsatisfied; 3 slightly satisfied; 4 satisfied; 5 very satisfied. Safety variable: Overall safety was rated by a physician on a 5‐point scale: 1 ‘one or more serious adverse drug reactions’; 2 ‘treatment caused problems, more than three non‐serious adverse drug reactions per treatment, daily life activity was impaired’; 3 ‘treatment slightly tolerated, less than three non‐serious adverse drug reactions per treatment, slight impairment of daily life activity’; 4 ‘treatment well tolerated, less than three non‐serious adverse drug reactions per treatment, no impairment of daily life activity’; 5 ‘treatment very well tolerated, no adverse drug reactions’. Other safety variables were changes in vital signs, physical examination, ECG and clinical laboratory measures
Funding sources	Quote "The study was funded by Kreussler." Quote "All investigators appreciate the kind donation by Sigvaris, Switzerland, in providing each patient with compression stockings class II and the necessary support. We also thank Excel Pharma Studies (Beijing, People’s Republic of China) for helping to conduct the study. Trilogy Writing and Consulting GmbH (Frankfurt, Germany) provided medical writing support on behalf of Kreussler."
Declarations of interest	Quote "Drs Schliephake and Otto were employees of Kreussler. Dr Mark Malouf has served as a consultant for Kreussler. Prof. Zhang Jiwei, Prof. Jing Zaiping and Prof. Yong‐quan Gu received research support as investigators in this study sponsored by Kreussler."
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	States "randomised", no details given
Allocation concealment (selection bias)	Unclear risk	No details given
Blinding of participants and personnel (performance bias) All outcomes	Low risk	They suggest blinding, confirmed by study author
Blinding of outcome assessment (detection bias) All outcomes	Low risk	They suggest blinding, confirmed by author
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Two patients assigned to polidocanol 1% and one patient assigned to placebo did not receive any study medication and were therefore excluded from the safety population (n = 285)."
Selective reporting (reporting bias)	Unclear risk	No details given
Other bias	Unclear risk	No details given

BMI: body mass index
CEAP: Clinical, Etiological, Anatomical and Pathophysiological (CEAP) classification system for chronic venous disorders
CG: chromated glycerin
CGX:chromated glycerin mixed
DVT: deep vein thrombosis
ECG: electrocardiogram
FPDL: following pulsed dye laser
ICG:indocyanine green
KTP: potassium titanyl phosphate
Nd:YAG: neodymium‐doped yttrium aluminium garnet
NIR: near‐infrared
PAD: peripheral arterial disease
PE: pulmonary embolism
POL: polidocanol
QoL: quality of life
SD: standard deviation
SF‐36: short form‐36 (QoL questionnaire)
STS: sodium tetradecyl sulfate
VAS: visual analogue scale
VDS: venous dysfunction score