Bertanha 2017.

Study characteristics
Methods	Study design: prospective, randomised, triple‐blind, controlled, parallel‐group clinical trial Method of randomisation: "Participants were randomly assigned using an open‐source, web‐based randomisation software (Stat Trek, http://stattrek.com/statistics/random‐number‐generator.aspx) to 1 of 2 treatment groups: group 1 to receive 0.2% polidocanol diluted in 70% hypertonic glucose; group 2 to receive 75% hypertonic glucose. The computer generated allocation sequence was kept by an independent nurse, who prepared opaque, sealed envelopes for each group. The nurse prepared the medications in a room separate from the treatment room." Blinding: participant ‐ yes; treating doctor ‐ yes; outcome assessors ‐ yes Power calculation: yes Total number of participants: 93 Total number of procedures: 93 Treatment localisation: lower limbs Number of exclusions post‐randomisation: none Number of withdrawals and reasons: none
Participants	Setting: outpatient site Country: Brazil Gender: women. "The study population consisted of a calculated sample of adult women consecutively recruited among patients seeking treatment at the specialized out patient clinic of our institution" Age: range 24 ‐ 62 Inclusion criteria; eligible participants were all women aged 18 to 69 years who had at least 1 reticular vein with a minimum length of 10 cm in 1 of their lower limbs with mild venous disease classified as CEAP C1, and all were available to attend the appointments Exclusion criteria: venous disease with a CEAP clinical class other than C1, pregnancy or puerperium, allergy to polidocanol or glucose, restricted mobility, PAD, diabetes mellitus, uncontrolled systemic disorders, dermatitis at the treatment site, asthma, migraine, previous DVT, family history of DVT, acute thrombophlebitis, known thrombophilia or any hypercoagulable state, and use of anticoagulants. Patients who failed to attend the treatment session or the follow‐up visits were also excluded
Interventions	Treatment 1: 0.2% polidocanol diluted in 70% hypertonic glucose Treatment 2: 75% hypertonic glucose The treatment area on the participant’s lower limb was defined as a rectangle of approximately 600 cm2 (25 cm long × 15 cm wide) on the lateral aspect of the distal midthigh and the proximal and middle leg of 1 of the limbs. The lower limbs were photographed before and after treatment using a high‐definition digital camera All sclerotherapy procedures were performed by the same physician. Both medications were in liquid form and identical in appearance within the syringes (colourless, odourless, and with similar viscosity). The maximum volume per puncture was 0.3 mL, and punctures were performed until whitening of the reticular veins occurred in the treatment area. After the procedure, elastic compression bandages (Atadress; Adamed) were applied directly over the treated area for 24 hours Duration of follow‐up: 60 days Use of compression: elastic compression bandage
Outcomes	The primary efficacy end point was complete elimination of the reticular veins by 60 days after sclerotherapy treatment with the study medications. To assess this outcome, the reticular veins were measured on images obtained before treatment (day 0) and after treatment (day 60) using ImageJ software. The linear measurements of reticular veins before treatment and residual veins after treatment were captured in pixels, which were then converted to millimetres. Each image was analysed by 2 independent observers who were blinded to the medication used. The safety outcomes were analysed at each post‐treatment visit for the occurrence of serious adverse events (chest pain, transient neurological abnormalities, anaphylaxis, accidental arterial puncture, tissue necrosis, DVT, and PE), minor adverse events (scars, cough, superficial thrombophlebitis, telangiectatic matting, allergies, lipothymia, and scotomas), and particularly pigmentation running the course of the treated veins, which was analysed based on direct measurements performed on post‐treatment images using ImageJ software Secondary outcomes: skin colour, number of punctures, volume of medication used, occurrence of haematomas, residual veins in relation to pigmentation, comparison of current pain with pain at the time of previous treatments, treatment‐related cough, migraine, oedema, early (day 7) and late (day 60) phlebitis, telangiectatic matting, and lipothymia
Funding sources	No details provided
Declarations of interest	None declared
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants randomly assigned in a 1:1 ratio using open‐source, web‐based randomisation software (Stat Trek, http://stattrek.com/statistics/random‐number‐generator.aspx)
Allocation concealment (selection bias)	Low risk	Quote: "The computer generated allocation sequence was kept by an independent nurse,who prepared opaque, sealed envelopes for each group. The nurse prepared the medications in a room separate from the treatment room."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Both medications were in liquid form and identical in appearance within the syringes (colourless, odourless, and with similar viscosity)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Each image was analysed by 2 independent observers who were blinded to the medication used. Still blindly, the safety outcomes were analysed at each post treatment visit for the occurrence of serious adverse events."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Of 106 eligible participants, 51 were randomised to receive 0.2% polidocanol diluted in 70% hypertonic glucose; in this group 1 did not receive allocated intervention and 7 lost to follow‐up; and 55 to receive 75% hypertonic glucose alone, in this group 1 did not receive allocated intervention and 4 lost to follow‐up
Selective reporting (reporting bias)	Unclear risk	No details given
Other bias	Unclear risk	No details given