Biland 1982.

Study characteristics
Methods	Study design: randomised, double‐blind, placebo‐controlled Method of randomisation: not stated Exclusions post randomisation: none Losses to follow‐up: 14/70 (20%)
Participants	Country: Germany Setting: hospital Number: 70 patients Age: mean 43 ± 13 years diosmine group; mean 39 ± 12.5 years placebo group Gender: 7 M:49 F Inclusion criteria: symptoms related to CVI and oedema Exclusion criteria: phlebitis, venous thromboses, post‐thrombotic syndrome, ulcus cruris, heart insufficiency, recent sclerotherapy or venous stripping, trauma, neuropathy, arthrosis, pregnancy
Interventions	Treatment: diosmine 450 mg plus hesperidin 50 mg, 2 capsules twice a day Control: placebo Duration: 28 days Follow‐up: 28 days
Outcomes	Primary Symptoms ‐ pain, cramps, swelling, restless legs measured by an ordinal scale (0 to 2) Oedema ‐ circumference of ankle and calf Secondary Clinical assessment by participants and doctors Side effects
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "The study was double‐blind, randomized, placebo with Daflon" Comment: no method of randomisation stated
Allocation concealment (selection bias)	Low risk	Quote: "Placebo tablets were given in indistinguishable numbered packaging" Comment: Indistinguishable number packaging ensures a fair method of 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: numbers of participants in each group reported, along with participants excluded after randomisation,reasons for exclusion and information on compliance
Selective reporting	Low risk	Comment: no published 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