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Thromb Haemost 1989; 62(03): 826-829
DOI: 10.1055/s-0038-1651011
Original Article
Schattauer GmbH Stuttgart

A Double Blind Three Center Clinical Trial on the Short-Term Efficacy of 0-(β-Hydroxyethyl)-Rutosides in Patients with Post-Thrombotic Syndrome

A B de Jongste
1   The Department of Surgery, University Hospital Leiden and Rode Kruis Ziekenhuis, Den Haag, The Netherlands
,
J J C Jonker
2   Thrombosis Centre, Rotterdam, The Netherlands
,
M V Huisman
3   Centre for Haemostasis, Thrombosis and Atherosclerosis Research, Academic Medical Centre, University of Amsterdam, The Netherlands
,
J W ten Cate
3   Centre for Haemostasis, Thrombosis and Atherosclerosis Research, Academic Medical Centre, University of Amsterdam, The Netherlands
,
A J Azar
4   Department of Clinical Epidemiology, Erasmus University of Rotterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 23 August 1988

Accepted after revision 24 May 1989

Publication Date:
30 June 2018 (online)

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Summary

A multi-centre, double blind randomized clinical triatr was designed to assess the efficacy and safety of orally administered 0-(β-hydroxyethyl)-rutosides (HR) capsules in the treatment of L0L patients with post-thrombotic syndrome. Seventeen patients were excluded from the analysis for violation of the study protocol, 4l received HR capsules (I,200 mg/day) and 43 placebo.

Mean follow-up scores at the 4th and 8th week show that the HR patients displayed an improved state of tiredness as compared to the placebo's. The mean circumference of the calf for the HR group decreased from 390 (± 33) mm at visit one to 382 (± 33) mm at visit three, with a mean circumference reduction of 8.7 (± 8) mm, compared to a steady placebo circumference of 387 (± 31) mm at all 3 visits with a mean circumference reduction of only 2 mm (± 9). The estimated treatment effect at week 8 was −6.7 ffiffi, 95% confidence interval (−10.3, −3.0).

The mean circumference of the ankle, decreased from 243 (± 20) mm to 238 (± 20) mm at the 4th week, contrasted with a constant placebo circumference of.24l (± 22) mm at both visits. The estimated treatment effect at week 4 was-5.4 ffiffi, 95% confidence intenral (−10.2, −0.6). However, at week 8, the estimated treatment effect was only −3.4 mm; 95% corrfidence interval (−8.6, + 1.8).

In conclusion, HR capsules may show an improvement in the clinical symptoms and may show a mean circumference reduction of the calf and ankle at the 8th week, in patients with postthrombotic syndrome.

Keywords

Post-thrombotic syndrome - Deep vein thrombosis - Chronic venous insufficiency - 0-(β-hydroxyethyl)-rutosides
 

  • References

  • 1 Negus D. The post-thrombotic syndrome. Ann R Coll Surg Engl 1970; 47: 092-105
    PubMedGoogle Scholar
  • 2 Ouvry P. Deep venous thrombosis of the leg. Clinical and therapeutic aspects. Phlebology 1982; 35: 597-605
    PubMedGoogle Scholar
  • 3 Linton RR. The post-thrombotic ulceration of the lower extremities: its etiology and surgical treatment. Ann Surg 1953; 138: 415
    CrossrefPubMedGoogle Scholar
  • 4 Gjoeres J. The incidence of venous thrombosis and its sequelae in certain districts of Sweden. Acta Chir Scand (Suppl) 1956; 206: 88
    PubMedGoogle Scholar
  • 5 Da Silva A, Widmer LK. et al. Varicose veins and chronic venous insufficiency. Vasa 1974; 3: 118-125
    PubMedGoogle Scholar
  • 6 Miettinen O, Nurminen M. Comparative analysis of two rates. Stat Med 1985; 4: 213-226
    CrossrefPubMedGoogle Scholar
  • 7 Jones NA G. et al. A physiological study of elastic compression stockings in venous disorders of the leg. Br J Surg 1980; 67 (08) 569-572
    CrossrefPubMedGoogle Scholar
  • 8 Browse NL, Gray L, Jarrett PE M, Morland M. Blood and vein-wall fibrinoloytic activity in health and vascular disease. Br Med J 1977; 1: 478
    CrossrefPubMedGoogle Scholar
  • 9 Arturson G. Effects of 0-(beta-hydroxyethyl)-rutosides (HR) on the increased microvascular permeability in experimental skin burns. Acta Chir Scand 1972; 138: 111-117
    PubMedGoogle Scholar
  • 10 Svensjoe E, Arfors KE, Arturson G. Effect of inhibition of PGE2-activity on FITC-dextran permeability in the hamster micro vasculature. Bibl Anat 1975; 13: 303-304
    PubMedGoogle Scholar
  • 11 Hilton JF G. Effects of HR upon post-bum plasma volume loss in the non-resuscitated dog. Bums 1981; 7: 211-214
    PubMedGoogle Scholar
  • 12 Hilton JF G. Effects of beta-hydroxyethylrutosides (HR) administered post bum after thermal-injury-induced plasma volume loss in the nonresuscitrated dog. Bums 1982; 8: 391-394
    PubMedGoogle Scholar
  • 13 Gerdin B, Svensjoe E. Inhibitory effect of the flavonoid 0-(beta-hydroxyethyl)-rutoside on increased microvascular permeability induced by various agents in rat skin. Int J Microcir Clin Exp 1983; 2: 39-46
    PubMedGoogle Scholar
  • 14 Blumberg S, Clough G, Michel CC. Effects of hydroxyethyl rutosides upon the permeability of single capillaries in the frog mesentery. Br J Pharmacol 1989; 96: 913-919
    CrossrefPubMedGoogle Scholar
  • 15 Roztocil K, Fisher A, Novak P, Razgova L. The effect of 0-(beta-hydroxyethyl)-rutosides (HR) on the peripheral circulation in patients with chronic insufficiency. Eur J Clin Pharmacol 1971; 3 (04) 243-246
    CrossrefPubMedGoogle Scholar
  • 16 Chant AD B. The effect of Paroven (HR) on the clearance of sodium-24 from the subcutaneous tissues of the foot m patients with varicose veins. Vasa 1973; 2 (03) 288-291
    PubMedGoogle Scholar
  • 17 Roztocil K, Prerovsky I, Oliva I. The effect of hydroxyethylrutosides on capillary filtration rate in the lower limb of man. Eur J Clin Pharmacol 1977; 11: 435-438
    CrossrefPubMedGoogle Scholar
  • 18 Bergqvist D, Hallböök T, Lindblad B, Lindhagen A. A double-blind trial of 0-(beta-hydroxyethyl)-rutosides in patients with chronic venous insufficiency. Vasa 1981; 10 (03) 253-260
    PubMedGoogle Scholar
  • 19 Timeus C. The effect of oral 0-(beta-hydroxyethyl)-rutoside (HR) versus placebo on vessel wall permeability and selective permeability in the microcirculation of the skin in healthy volunteers. In: Phlebology '85. Negus D. et al. (eds). J Libbey & Co Ltd; London: 1986: 825-827
  • 20 Razgova L, Roztocil K, Halova J, Fischer A. The effect of 0-(beta-hydroxyethyl)-rutosides (HR) on peripheral blood vessels on the lower extremities in idiopathic oedema. Eur J Clin Pharmacol 1971; 3 (04) 247-251
    CrossrefPubMedGoogle Scholar
  • 21 Hishon S, Hunter JO, Rose JD. The effect of hydroxy ethylrutosides on albumin escape rate in cirrhosis. In: Hydroxyethylrutosides in Vascular Disease. Pulvertaft TB. et al. (eds). (R Soc Med Int Congr Symp Ser; 42). 1981: 55-59
    Google Scholar
  • 22 Tschopp M, Pometta D, Babel J. Diabetic retinopathy: study of the action of O-beta-hydroxyaethyl-rutosides (HR) by retinal fluores-ceinography. Diabetologia 1970; 6: 475-481
    CrossrefPubMedGoogle Scholar
  • 23 Hammersen F. The ultrastructural changes in the microcirculation in experimental oedema: a suitable morphological test model for the effect of vaso-active drugs. Biorheology 1970; 6: 343-351
    CrossrefPubMedGoogle Scholar
  • 24 Hammersen F, Moehring E. An ultrastructural study of the effect of HR on enzymatically induced alteration of capillary endothelia and erythrocytes in rats (phospholipase oedema). Dtsch Med J 1972; 23 (05) 406-409
    PubMedGoogle Scholar
  • 25 Hladovec J, Rossmann P. Circulating endothelial cells isolated together with platelets and the experimental modification of their counts in rats. Thromb Res 1973; 3 (06) 665-674
    CrossrefPubMedGoogle Scholar
  • 26 Hladovec J. Endothelial injury by nicotine and its prevention. Experientia 1978; 34: 1585
    CrossrefPubMedGoogle Scholar
  • 27 Prerovsky I, Hladovec J. Suppression of the desquamating effect of smoking on the human endothelium by hydroxyethylrutosides. Blood Vessels 1979; 16: 239-240
    PubMedGoogle Scholar
  • 28 Ten Cate JW, Van Haeringen NJ, Gerritsen J, Glasius E. Biological activity of a semisynthetic flavonoic, 0-(beta-hydroxyethyl)-rutoside: Light-scattering and metabolic studies of human red cells and platelets. Clin Chem 1973; 19 (01) 31-35
    PubMedGoogle Scholar
  • 29 Van Haeringen NJ, Glasius E, Ten Cate JW, Gerritsen J, Van Geet J. Effect of 0-(beta-hydroxyethyl)-rutoside on red cell and platelet functions in man. In: 7th Europ Conf Microcirc, Aberdeen 1972, Part II. Bibl Anat (Karger, Basel) 1973; 12: 459-464
    PubMedGoogle Scholar
  • 30 Schmid-Schönbein H, Volger E, Weiss J, Brandhuber M. Effect of 0-(beta-hydroxyethyl)-rutosides on the microrheology of human blood under defined flow conditions. Vasa 1975; 4 (03) 263-270
    PubMedGoogle Scholar
  • 31 Sonnenfeld T, Ekestroem S, Koul BL. Hydroxyethylrutosides during extracorporal circulation: effect on erythrocyte deformability. Scand J Thorac Cardiovasc Surg 1985; 19: 85-87
    PubMedGoogle Scholar
  • 32 Timeus C. Effect of a single i.v. dose of O-(beta-hydroxyethyl)-rutoside (HR) versus placebo on vessel wall permeability and selective permeability and on haemorheological parameters in patients with chronic venous insufficiency. In: Phlebology '85. Negus D. et al. (eds). J Libbey & Co Ltd; London: 1986: 828-830
  • 33 McEwan AJ, McArdle CS. Effect of hydroxyethylrutosides on blood oxygen levels and venous insufficiency symptoms in varicose veins. Br Med J 1971; 2: 138-141
    CrossrefPubMedGoogle Scholar
  • 34 Lund F. Fluorescein-angiographic studies of the effect of intravenous Venoruton on the cutaneous microcirculation in serious cases of arterial occlusion in the limbs. In: 0-(beta-hydroxyethyl)-rutoside. Voelter W, Jung G. (eds). Springer-Verlag; Berlin: 1983: 195
  • 35 Jelnes R, Gaardsting O, Holm A. Improvement of subcutaneous nutritional blood flow in the forefoot by hydroxyethylrutosides (Venoruton) in patients with arterial insufficiency: Case studies. Angiology 1986; 27 (03) 198-202
    PubMedGoogle Scholar
  • 36 Burnand KG. Effect of hydroxyethyl rutosides on transcutaneous P02 measurements. Abstracts presented at the UK Surgical Research Society London: July 1987
    Google Scholar
  • 37 Neumann HA M, van den Broek MJ T B. The effectiveness of 0-(beta-hydroxyethyl)-rutosides in chronic venous insufficiency. A double-blind study into the influence of O-(beta-hydroxyethyl)-rutosides on the TcP02 and light reflection rheography in patients with chronic venous insufficiency (CVI). Int Angiol (suppl) 1989; 4: 9
    PubMedGoogle Scholar