Rabe 2011.

Study characteristics
Methods	Study design: randomised, multi‐centre, double‐blind, placebo‐controlled Method of randomisation: table of random numbers Exclusions post randomisation: 22 (8%) Losses to follow‐up: 32/256 (12.5%)
Participants	Countries: Germany and Switzerland Setting: not stated Number: 256 patients Age: mean 53.2 ± 11.5 years treatment group; mean 53.5 ± 12.1 years placebo group Gender: 38 M:218 F Inclusion criteria: pitting oedema due to CVI (C3‐C5 according to CEAP classification) and ≥ 1 of the symptoms such as discomfort and pain Exclusion criteria: disease that imitates symptoms of CVI, cardiac insufficiency, ulceration of the lower leg, diabetes mellitus, hypertension, lymphoedema, sclerotherapy during the past 6 months, lipoedema, obesity (BMI > 30 kg/m2), disease of the gastrointestinal tract; female patients who were pregnant, lactating or of childbearing potential and not protected from pregnancy by a sufficiently reliable method; malignant disease
Interventions	Treatment: calcium dobesilate 1500 mg per day Control: matching placebo Duration: 56 days Follow‐up post treatment: 70 days Elastic stockings permitted
Outcomes	Primary Signs ‐ relative leg volume change in the most pathological leg assessed by a volumetric measurement with a calibrated tape and calculated by assimilating the lower leg volume to a truncated cone Secondary Signs ‐ change in leg perimeters Symptoms ‐ subjective symptoms (pain, discomfort, feeling of tired or heavy legs, tingling, itching and cramps) on a five‐point categorical scale. Pain and discomfort were assessed by 100‐mm visual analogue scales, and quality of life was assessed by chronic lower limb venous insufficiency (CIVIQ) Assessment of overall efficacy by participant and investigator
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization with blocks of four was used. The randomization list was produced by an independent person" Comment: Randomisation list ensures a random sequence
Allocation concealment (selection bias)	Low risk	Quote: "The study medication was packed in identical boxes marked with a randomization number each newly randomized patient was given the medication with the lowest randomization number available" Comment: Identical boxes with randomisation provision ensure proper allocation concealment
Blinding (patients)	Low risk	Quote: ".... or a matching placebo ... The study medication was packed in identical boxes..." Comment: Identical placebo ensures double‐blinding
Blinding (study researchers)	Low risk	Quote: "The study medication was packed in identical boxes marked with a randomization number each newly randomized patient was given the medication with the lowest randomization number available" ; ".... or a matching placebo ... The study medication was packed in identical boxes..." Comment: Identical placebo ensures double‐blinding
Blinding (outcome assessment)	Low risk	Quote: ".... or a matching placebo ... The study medication was packed in identical boxes..." Comment: Identical placebo ensures double‐blinding
Incomplete outcome data	Low risk	Comment: number in each group described, as were loss to follow‐up and participants who prematurely withdrew. Important characteristics and inclusion and exclusion criteria reported. ITT analysis conducted, but no methods used for imputation of missing values described
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