Belczak 2014.

Study characteristics
Methods	Study design: randomised, double‐blind, placebo‐controlled Method of randomisation: not stated Exclusions post randomisation: none Losses to follow‐up: 9/136 (6.6%)
Participants	Country: Brazil Setting: Department of Vascular Surgery of Sao Camilo Medical School Number: 136 patients Age: mean 52.8 ± 16.4 years active group; mean 50.6 ± 13.1 years placebo group Gender: 33 M:103 F Inclusion criteria: treatment‐naïve (no history of pharmacological or compression therapy), CVD (CEAP grades 2 to 5) Exclusion criteria: other conditions that might produce lower extremity‐related symptoms
Interventions	Treatments: micronised diosmine (450 mg) + hesperidin (50 mg), aminaftone (75 mg), coumarin (15 mg), troxerutin (90 mg) Control: placebo Duration: 112 days Follow‐up: 112 days Compression therapy: not used
Outcomes	Primary Quality of life Mean limb volumes Mean joint range of motion Secondary Not stated
Notes	Funding: all medications and placebos purchased by the investigators
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "The patients were randomly divided into four groups" Comments: no methods of randomisation described
Allocation concealment (selection bias)	Low risk	Quote: "All tablets (active and placebo) were randomly divided into numbered bottles by an external investigator..."
Blinding (patients)	Low risk	Quote: "All tablets (active and placebo) were randomly divided into numbered bottles by an external investigator, and the contents of each bottle were unmasked only at the time of statistical analysis"
Blinding (study researchers)	Low risk	Quote: "All tablets (active and placebo) were randomly divided into numbered bottles by an external investigator, and the contents of each bottle were unmasked only at the time of statistical analysis"
Blinding (outcome assessment)	Low risk	Quote: "Assessors were blind to the treatment groups"
Incomplete outcome data	Low risk	Comment: very few participants lost to follow‐up
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