Widmer 1990.

Study characteristics
Methods	Study design: randomised, double‐blind, placebo‐controlled Method of randomisation: randomisation list prepared by statistician Exclusions post randomisation: none Losses to follow‐up: 17/225 (7%)
Participants	Country: Switzerland Setting: hospital Number: 225 patients Age: 20 to 70 years Gender: 27 M:181 F Inclusion criteria: CVI grade I to II (alterations in pigmentation, with or without subcutaneous veins, oedema and symptoms of the disease) Exclusion criteria: CVI grade III with open or healed varicose ulcer; venous surgery during past 12 months or sclerotherapy during past 6 months; symptomatic peripheral arterial occlusion; renal or cardiac insufficiency; lymphoedema; diabetes; hypertension; overweight; pregnancy; compression therapy or drugs that might interfere with clinical results (diuretics); intolerance to the active drug of the study
Interventions	Treatment: calcium dobesilate 1500 mg per day Control: placebo Duration: 28 days Follow‐up: 28 days
Outcomes	Primary Symptoms ‐ pain, cramps, heaviness, paraesthesia and restlessness measured by a visual analogue scale Signs ‐ oedema measured by circumference of ankle Discomfort measured as the sum of frequencies of symptoms: pain, heaviness, paraesthesia and restlessness Total score of all observed symptoms Secondary Overall efficacy assessed by physician and participant Side effects
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The patients were treated for 28 days with either Doxium or placebo at the dosage of 3 capsules daily, according to a randomization list prepared by the statistician" Comment: randomisation list assumed to be a fair method of assuring a random sequence
Allocation concealment (selection bias)	Unclear risk	Comment: no methods described for allocation concealment
Blinding (patients)	Unclear risk	Comment: no information given about methods used for blinding
Blinding (study researchers)	Unclear risk	Comment: no information given about methods used for blinding
Blinding (outcome assessment)	Unclear risk	Comment: no information given about methods used for blinding
Incomplete outcome data	Low risk	Comment: number of participants in each group described, including most important characteristics and inclusion and exclusion criteria. In addition, reasons for excluding participants after randomisation given, along with number of participants. Number compliant with medication provided, along with adverse events
Selective reporting	Low risk	Comment: no protocol identified, and no differences between outcomes reported in the methods section and those reported in the results section
Other bias	Low risk	Comment: none detected