Arcangeli 2000.

Study characteristics
Methods	RCT. Design: parallel group design. Country and setting: Italy; clinical centre. Ethics approval by the 'Ministry of Health'. Treatment duration: 2 months after a 2‐week run‐in period during which neither drugs acting on the cardiovascular system nor diuretics, analgesics or anti‐inflammatory compounds were allowed. No follow‐up after end of treatment.
Participants	Total participants: 40 (20 in each group). Inclusion criteria: adults with CVI as a result of deep vein thrombosis or idiopathic venous lymphatic deficiency. Diagnosis was based on clinical judgement. Exclusion criteria: not reported. Baseline characteristics: Pycnogenol® group: 25% males; age, mean (SD) 57.95 (12.78) years (range 34 to 74 years). Control group: 40% males; age, mean (SD) 61.40 (10.62) years (range 30 to 70 years).
Interventions	Treatment: Pycnogenol® 100 mg 3x per day for 2 months. Control: "visually matched" placebo; 3x per day for 2 months. Route of administration: not reported; assumed to be oral. Concomitant medication: participants were not allowed to take drugs which act upon the cardiovascular system, diuretics, or analgesic and anti‐inflammatory combinations during the treatment period. Diet: a standard diet determined according to participants' energy requirements had to be followed.
Outcomes	Symptom scores (heaviness; swelling; pain of legs): collected at baseline, after 30 days and after 60 days of treatment; assessed by a clinical symptomatology score system where 0 = absent, 1 = light, 2 = moderate and 3 = severe; the percentage of participants who had disappearance of each symptom was also calculated. Venous blood flow: collected at baseline, after 30 and after 60 days of treatment; measured with a hand‐held Doppler ultrasound. Clinical assessment of efficacy: collected at 60 days after treatment; assessed by a semi‐qualitative scale where 1 = poor, 2 = moderate, 3 = good and 4 = very good. Clinical tolerability: participants were asked to report "adverse effects" anytime during treatment. Biochemical tolerability: blood samples were collected at baseline and after 60 days of treatment for blood tests (haematology, blood chemistry, liver functions, renal function); the unit of measurement for each blood test is specified in the article.
Notes	Funding source: not reported. Study date: 1989.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"...patients were randomly divided". However, the randomisation method is not reported.
Allocation concealment (selection bias)	Unclear risk	Not reported.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not reported.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not reported.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not reported whether all randomised participants completed the study, i.e. whether data from all participants for all outcomes were collected.
Selective reporting (reporting bias)	High risk	Protocol not available; not all outcomes reported in the 'Results' section were pre‐specified in the 'Methods' section outcomes reported in the Results section were not pre‐specified in the Methods section.
Other bias	Unclear risk	Funding source not reported.
Was a paired analysis being used?	Low risk	Not applicable.
Is the cross‐over design suitable?	Low risk	Not applicable
Are data of both periods available?	Low risk	Not applicable.
Was there no carry‐over effect?	Low risk	Not applicable.
Are the results comparable to those from parallel group trials?	Low risk	Not applicable.