Parrado 1999.

Study characteristics
Methods	Study design: randomised, double‐blind, placebo‐controlled Method of randomisation: table of random numbers Exclusions post randomisation: none Losses to follow‐up: none
Participants	Country: Argentina Setting: hospital Number: 60 patients Age: 30 to 70 years Gender: 16 M:44 F Inclusion criteria: CVI, stages I to II of the Widmer classification (pigmentation, oedema, varicoses and symptoms) Exclusion criteria: elastic stockings; urgent surgical treatment or venous surgical treatment or sclerotherapy in previous 6 months; cardiac, renal or hepatic insufficiency; anti‐migraine drugs; analgesics; NSAIDs; diuretics or cardiovascular drugs; pregnant women or women who had given birth during previous 3 months
Interventions	Treatment: Ruscus aculeatus with hesperidin and vitamin C 300 mg per day Control: placebo Duration: 60 days Follow‐up: 60 days
Outcomes	Primary Symptoms ‐ heaviness, pain, cramps, tiredness, pruritus, tingling sensation, swelling, measured by means of an ordinal scale from 0 to 3 (from no symptoms to severe symptoms) Participants' global assessment by a qualitative scale Signs ‐ venous inflammation, pigmentation, trophic ulceration and oedema (circumference of ankle measured by a medical ribbon and by the ordinal scale) Secondary Not stated
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The study was double‐blind and patients were randomly allocated to be included in one of two parallel groups by using a table of random numbers"
Allocation concealment (selection bias)	Unclear risk	Comment: no methods of allocation concealment described
Blinding (patients)	Low risk	Quote: "Bottles, identical in form and presentation contained dobesilate calcium or placebo, according to a randomization code that was opened until the end of experiment" Comments: Identical presentation of intervention and control groups ensures double‐blinding
Blinding (study researchers)	Low risk	Quote: "Bottles, identical in form and presentation contained dobesilate calcium or placebo, according to a randomization code that was opened until the end of experiment"; "Neither the patient nor the medical staff did not know the nature of the substance administered, thereby satisfying the conditions of a double‐blind trial" Comments: Identical presentation of intervention and control groups ensures double‐blinding
Blinding (outcome assessment)	Low risk	Quote: "Bottles, identical in form and presentation contained dobesilate calcium or placebo, according to a randomization code that was opened until the end of experiment"; "Neither the patient nor the medical staff did not know the nature of the substance administered, thereby satisfying the conditions of a double‐blind trial" Comments: Identical presentation of intervention and control groups ensures double‐blinding
Incomplete outcome data	Low risk	Comment: no losses reported
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