Rabe 2010.

Study characteristics
Methods	Study design: randomised, double‐blinded, placebo‐controlled, multicentre study comparing polidocanol, sodium tetradecyl sulfate and isotonic saline (placebo) Method of randomisation: computerised randomisation procedure to allocate patients to 3 treatment groups in a ratio of 3:2:1 (polidocanol: sodium tetradecyl sulfate: isotonic saline placebo) Blinding: patient ‐ yes, treating doctor ‐ yes, independent photo assessors ‐ yes Power calculation: not stated Number of patients randomised: 360 (160 with spider veins) Number of patients analysed: for spider veins: 157 patients in full analysis and 127 patients in per protocol analysis Number of exclusions post randomisation: for spider veins: 30 excluded from full analysis due to protocol deviations Number of withdrawals and reasons: for spider veins: 1 withdrawn due to noncompliance with protocol; 2 lost to follow up Source of funding: stated in the abstract from Phlebology 2009 only and not the Phlebology 2010 publication of this research: study funded by Kreussler (manufacturer of polidocanol)
Participants	Setting: 19 general practice and hospital locations Country: Germany Total number: 316 (157 with telangiectasias) Age: mean age 43.5 SD 11.5 years (range from 18 to 70) Sex: 308 female and 8 male Mean height: 168 SD 6.5 cm Mean BMI: 23.8 SD 3.7 kg/m² Inclusion criteria: patients aged between 18 to 70 years with C1 (CEAP 1) veins Exclusion criteria: patients with C2 to C6 venous insufficiency, CEAP classifications Es and Ec, AD and PO, those who had sclerotherapy in ipsilateral leg in last 12 weeks or contralateral leg in last 4 weeks, laser treatment, surgery, history of acute or major superficial or deep vein thrombosis, coagulopathies, major leg edema, arterial occlusive disease, clinically relevant ECG abnormalities, acute severe systemic disease or poor general health, severe generalized infection, acute febrile states, symptoms of microangiopathy or neuropathy, inflammatory disease in the treatment area
Interventions	Patients were randomised in 3:2:1 ratio to treatment with (for spider veins): 1) 0.5% POL 2) 1% STS 3) isotonic saline placebo Patients were asked to wear a compression stocking on the treated leg during waking hours and to remove it 24 hours prior to the next treatment Duration: 26 weeks after last of 3 possible injection visits each 3 weeks apart (so up to maximum of 32 weeks)
Outcomes	Primary outcome: 1) Efficacy: evaluation of digital photos taken pre‐treatment, 12 weeks post and 26 weeks post with a specially designed digital imaging system for the study were evaluated by the investigator and two independent blinded medical experts. They were rated on 5‐point scale (worse than before, same as before, moderate improvement, good improvement, complete treatment success) Secondary outcomes: 1) Patient satisfaction: patient assessed satisfied based on comparing the baseline photo to results at weeks 12 and 26 on a 5 point scale (very unsatisfied, somewhat unsatisfied, slightly satisfied, satisfied, very satisfied) 2) Adverse events: injection site irritation, discolouration, warmth, necrosis, ulcer, erythema, inflammation, hematoma, neovascularisation, itching, scar, pain
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computerised randomisation procedure
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding (performance bias and detection bias) All outcomes	Low risk	"Syringes for injection were prepared on site by a dedicated non‐blinded person." "Photo images were investigated by the investigator and two blinded independent observers."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Explanations provided for withdrawals and exclusions. A full analysis and per protocol analysis were performed.
Selective reporting (reporting bias)	High risk	Data for telangiectasias and reticular veins were not separated in the publication; however, we were able to obtain separate data from the trial authors.
Other bias	Unclear risk	The study was funded by Kruessler, and 2 of the study authors are employees of Kruessler, as per the study abstract published in Phlebology in 2009. These affiliations were not mentioned in the Phlebology 2010 publication. The dose of STS 1% was used "as requested by the FDA and authorized by the US‐labelling." The authors acknowledge in their discussion that "this may not be completely in line with current use in the USA where it seems to be common practice to dilute this drug." They attribute the high STS concentration to the higher side‐effects and lower patient satisfaction seen in this study.