The LONFLIT4-Venoruton Study: a randomized trial--prophylaxis of flight-edema in venous patients.

The aim of this independent study was to evaluate the protective effects, on the development of flight edema, of Venoruton. The study included patients with venous disease traveling in economy in long-haul flights (9 hours). Edema is a relevant aspect of long-haul flights affecting both patients with venous disease and normal subjects. Microcirculatory variations during flights cause a microangiopathy and biochemical and coagulation alterations. This condition may be defined as flight microangiopathy. A group of 203 subjects with chronic venous disease (uncomplicated varicose veins) at low-medium risk for DVT were contacted; 43 subjects were excluded for several nonmedical, travel-related problems or inconvenient evaluation time; the remaining 160 were randomized, after informed consent, into 2 groups to evaluate 2 prophylaxes in 7-8-hour, long-haul flights: The treatment group received Venoruton (hydroxyethyl rutosides) 1 g twice daily for 3 days (2 days before the flight and the day of the flight). The control group received comparable placebo. The edema score was based on the edema tester, ankle circumference, volume measurements, subjective swelling, and discomfort score. Items 1, 4, and 5 are based on an analogue scale line (1 to 10) directly defined by the subjects before and after the flights. Of the 160 included subjects 139 completed the study. Dropouts (21) were due to poor compliance, traveling, and/or connection problems (11 in the control group, 10 in the treatment group). Age and sex distribution were comparable in the 2 groups as were risk factors distributions. The level of edema at inclusion was comparable in the 2 groups of subjects. After the flight there was an average score of 7.2 (sd 2) in the control group, while in the Venoruton group the score was on average 3.2. (sd 1.1) (p < 0.05), 2.25 times lower than in the control group (p < 0.05). In the control group 89% of the subjects had an evident increase in ankle circumference and volume, which was clearly visible at inspection and associated with discomfort. In the Venoruton group edema was clearly present in 12% of subjects (associated with discomfort between 5 and 7 on the analogue scale line) and it was mild-moderate, not associated with symptoms (pain, discomfort between 2 and 4 on the analogue scale line). Therefore, the control of flight edema with Venoruton was clear both considering parametric data (circumference and volume) and nonparametric (analogue scale lines) measurements. The combined evaluation of the edema score is significantly favorable for patients treated with Venoruton. No deep vein thrombosis or superficial vein thrombosis was observed in this study.

The LONFLIT4-VENORUTON study: a randomized trial prophylaxis of flight-edema in normal subjects.

This study evaluated the protective effects of Venoruton on the development of flight edema in normal subjects travelling in economy in long-haul flights (8-9 hours). Edema is a relevant aspect of long-haul flights affecting both venous patients and normal subjects. Edema and flight microangiopathy were studied in a group of 164 subjects randomized (after informed consent) into two groups to evaluate prophylaxis in 8- to 9-hour flights. The treatment group received Venoruton (hydroxyethyl rutosides) 1 g twice daily for 3 days (2 days before the flight and the day of the flight). The control group received comparable placebo. Edema was evaluated with a composite edema score based on the edema tester, on the measurements of ankle circumference, volume measurements, subjective swelling, and on a discomfort score. Items 1, 4, and 5 are based on an analogue scale line (1 to 10) directly defined by the subjects before and after the flights. Of the included subjects, 151 completed the study. Dropouts were due to poor compliance, travelling, or connection problems. Age and gender distribution were comparable in the two groups as were risk factor distributions. The level of edema at inclusion was comparable in the two groups of subjects. After the flight there was an average score of 6.7 (SD 1.7) in the control group, while in the Venoruton group the score was on average 3 (SD 1.1) (p < 0.05). In the control group 77% of the subjects had an evident increase in ankle circumference and volume, which was clearly visible at inspection and associated with discomfort. In the Venoruton group, edema was clearly present only in 8% of subjects (associated with discomfort rated between 3 and 6 on the analogue scale line) and it was mild, not associated with symptoms. Therefore the control of flight edema with Venoruton was clear both considering parametric data (circumference and volume) and non-parametric (analogue scale lines) measurements. The combined evaluation of the edema score is significantly favorable for subjects under prophylaxis with Venoruton.

Oxerutins (Venoruton): efficacy in chronic venous insufficiency--a double-blind, randomized, controlled study.

The aim of this study was to confirm the clinical efficacy of oxerutins by evaluation of venous parietal tone and microvascular perfusion in a double-blind, randomized, placebo-controlled study. The study included 60 patients. Venous tone was evaluated by air-plethysmography (APG) in patients with venous insufficiency (CVI). Forty patients were treated with oxerutins and 20 with placebo for 4 weeks. The dose of the first 2 weeks was higher than that of the following 2 weeks. The age range was between 18 and 65 years. Randomized patients received treatment (oxerutins or placebo) according to the grade of CVI. Patients with grade I CVI received 2 g/day in the first 2 weeks of treatment and 1 g/day in the following weeks. Patients with grade II CVI received 3 g/day in the first 2 weeks and 2 g/day in the following 2 weeks. Visits were scheduled at baseline time (visit 1), at 2 weeks (visit 2) and at 4 weeks (visit 3). They were assessed with the following: (1) APG; (2) light reflection rheography (LRR); (3) capillaroscopy; (4) liquid crystals thermography. CVI signs/symptoms--heavy legs, edema, paresthesia, and cramps--were evaluated following a 4-point rating scale (0 = no symptom; 3 = severe symptoms). At visit 3 a final opinion on efficacy was provided by both patients and investigators, based on a 4-point scale (none, fairly good, good, excellent). The two groups were homogeneous for age, sex, and clinical distribution. The changes in venous capacity, were significant (p<0.01) in the oxerutins group at visits 2 and 3; values in the placebo group remained unchanged. The changes in LRR were significant in the treatment group at visits 2 (p<0.05) and 3 (p<0.01); values in the placebo group remained unchanged. Changes in temperature were significant in the oxerutins group at visits 2 (p<0.05) and 3 (p<0.01); changes in the placebo group were not significant at the end of the study. Capillaroscopy showed an improvement in patients treated with oxerutins. The results of the analysis of signs/symptoms favored active treatment. The overall effects of oxerutins were significantly better than the effects of placebo. Considering both noninvasive tests and clinical evaluation, oxerutins is effective in controlling chronic venous hypertension, without side effect, and with good tolerability.