Arcangeli 2000.

Study characteristics
Methods	Study design: randomised, double‐blind, placebo‐controlled Method of randomisation: not stated Exclusions post randomisation: none Losses to follow‐up: none
Participants	Country: Italy Setting: clinical centre Number: 40 patients Age: mean 57.95 ± 12.78 years pycnogenol group; mean 61.40 ± 10.62 years placebo group Gender: 13 M:27 F Inclusion criteria: symptomatic CVI as a consequence of deep venous thrombosis or idiopathic venous lymphatic deficiency Exclusion criteria: cardiovascular, diuretics, analgesic or anti‐inflammatory drugs
Interventions	Treatment: French maritime pine bark extract, 100 mg 3 × per day Control: placebo Duration: 69 days Follow‐up: 60 days
Outcomes	Primary Symptoms ‐ heavy legs, pain and swelling measured by means of a semiquantitative scale (0 to 3) Percentage of participants showing disappearance of each symptom Secondary Venous blood flow measured by Doppler ultrasound Tolerability Global assessment by physicians at the end of the trial
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "After the 2‐week run‐in period, the patients were randomly divided into two groups and assigned to a treatment with Pycnogenol, 100 mg × 3/day or a placebo for a period of 2 months" Comment: no method of randomisation stated
Allocation concealment (selection bias)	Unclear risk	Comment: no method of allocation concealment stated
Blinding (patients)	Low risk	Quote: "The placebo visually matched the test drug" Comment: Identical placebo ensures double‐blinding
Blinding (study researchers)	Low risk	Quote: "The placebo visually matched the test drug" Comment: Identical placebo ensures double‐blinding
Blinding (outcome assessment)	Low risk	Quote: "The placebo visually matched the test drug" Comment: Identical placebo ensures double‐blinding
Incomplete outcome data	Low risk	Comment: no exclusions post randomisation and no losses to follow‐up described
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