Cornu‐Thenard 1985.

Study characteristics
Methods	Study design: randomised, multi‐centre, double‐blind, placebo‐controlled Method of randomisation: random distribution of numbered batches Exclusions post randomisation: not stated Losses to follow‐up: not stated
Participants	Country: France Setting: not stated Number: 83 patients Age: 20 to 65 years; mean 43.73 ± 11.92 years active group; mean 43.55 ± 11.42 years placebo group Gender: 6 M:77 F Inclusion criteria: symptoms related to CVI Exclusion criteria: severe damage to venous musculature requiring urgent treatment ‐ surgery or sclerosis; surgical operation on venous or deep or superficial vein thrombosis in the past year; sclerosis or heavy support bandages (light support bandages not excluded), major trophic lesions, Raynaud's syndrome, arteritis, lymphoedema, renal or cardiac insufficiency; anti‐migraine treatment, analgesic or anti‐inflammatory treatment, diuretic treatment, low‐sodium diet, treatment for cardiovascular system (except nifedipine)
Interventions	Treatment: extract Ruscus aculeatus 75 mg plus hesperidin 75 mg plus ascorbic acid 50 mg per day (Cyclo 3) Control: placebo Duration: 60 days Follow‐up: 60 days Light compression therapy allowed
Outcomes	Primary Symptoms ‐ pain, cramps, heavy legs, paraesthesia, pins and needles, burning and restless legs measured by a semiquantitative scale (0 to 3) Secondary Doctor's global assessment Side effects
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A double‐blind comparative study against placebo, using two groups treated in parallel, after random distribution of numbered batches of the two treatments to be compared" Comment: seems like a fair method of randomisation was conducted
Allocation concealment (selection bias)	Unclear risk	Comment: no information given about methods used for allocation concealment
Blinding (patients)	Low risk	Quote: "The two products to be compared were presented in the form of identical capsules for both Cyclo 3 and placebo" Comment: Identical placebo ensures a fair method used for double‐blinding
Blinding (study researchers)	Low risk	Quote: "The two products to be compared were presented in the form of identical capsules for both Cyclo 3 and placebo" Comment: Identical placebo ensures a fair method used for double‐blinding
Blinding (outcome assessment)	Low risk	Quote: "The two products to be compared were presented in the form of identical capsules for both Cyclo 3 and placebo" Comment: Identical placebo ensures a fair method used for double‐blinding
Incomplete outcome data	Unclear risk	Quote: no information provided about participants who withdrew prematurely from the trial
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