Liposomal Heparin Spray: A New Formula in Adjunctive Treatment of Superficial Venous Thrombosis

Abstract

The objective of this study was to assess the efficacy and safety of liposomal heparin spray—a new formula of topical heparin delivery. This was a randomized, multicenter, controlled open clinical trial with 2 parallel groups. Forty-six outpatients with clinical signs of superficial venous thrombosis (SVT) were treated with either topical liposomal heparin spraygel (LHSG) (Lipohep Forte Spraygel, 4 puffs of 458 IU tid (n=22) or with low-molecular-weight heparin (LMWH) (Clexane 40 mg once a day (n=24), administered subcutaneously (sc). Main outcome measures were efficacy parameters (improvement of local symptoms—pain control and planimetric evaluation of erythema size, duplex Doppler assessment of thrombus regression) and safety parameters (documentation of adverse events, with particular reference to deep vein thrombosis [DVT] by duplex sonography, and patients’ and investigators’ assessment of drug tolerance). Patients’ and investigators’ subjective assessment of efficacy of treatment and change in basic biochemical parameters were defined as secondary outcome measures. Statistical analysis was performed with use of Wilcoxon test, Mann-Whitney U-test and Chi-square test. Regression of SVT-related symptoms, including pain, erythema, and thrombus presence, was shown as comparable in LHSG and LMWH groups. These results were corroborated by efficacy assessment by investigators and patients. Three cases of deep venous thrombosis in heparin spraygel and 1 in heparin sc group were reported. No significant adverse reactions were observed in the spraygel group, but 1 serious allergic reaction was observed in the LMWH group. Tolerance of new formula heparin was assessed as good. Heparin spraygel—a new topical mode of heparin application, seems a promising method of heparin delivery. This initial study has demonstrated comparable efficacy and safety of LHSG and LMWH in local treatment of SVT. These findings should be confirmed by further extensive study that will reach appropriate statistical power to support such conclusion, for despite heparin treatment, significant risk of DVT was demonstrated in both groups.

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References

Blumenberg RM , Barton E , Gelfand ML , et al : Occult deep venous thrombosis complicating superficial thrombophlebitis. J Vasc Surg 27:338-343, 1998.

Chengelis DL , Bendick PJ , Glover JL , et al : Progression of superficial venous thrombosis to deep vein thrombosis. J Vasc Surg 24:745-749, 1996.

Guex JJ : Thrombotic complications of varicose veins. A literature review of the role of superficial venous thrombosis. Dermatol Surg 22:378-382, 1996.

Bounameaux H , Reber-Wasem MA : Superficial thrombophlebitis and deep vein thrombosis. A controversial association. Arch Intern Med 157:1822-1824, 1997.

Martinelli I , Cattaneo M , Taioli E , et al : Genetic risk factors for superficial vein thrombosis. Thromb Haemost 82:1215-1217, 1999.

Van der Molen HR : [Ambulatory recurring or migrating phlebitis of subacute appearance (analysis of 30 cases)]. Phlebologie 30:65-81, 1977.

Kalodiki E , Nicolaides A : Superficial thrombophlebitis and low-molecular-weight heparins. Angiology 53:659-663, 2002.

Incandela L , De Sanctis MT , Cesarone MR , et al : Treatment of superficial vein thrombosis: Clinical evaluation of Essaven gel—a placebo-controlled, 8-week, randomized study. Angiology 52(suppl 3):S69-S72, 2001.

Belcaro G , Nicolaides AN , Geroulakos G , et al : Essaven Gel—review of experimental and clinical data. Angiology 52(suppl 3):S1-S4, 2001.

10.

Betz G , Nowbakht P , Imboden R , et al : Heparin penetration into and permeation through human skin from aqueous and liposomal formulations in vitro. Int J Pharmacol 228:147-159, 2001.

11.

Kim TD , Kambayashi J , Sakon M , et al : Metabolism of liposome-encapsulated heparin. Thromb Res 56:369-376, 1989.

12.

Betz G , Imboden R , Imanidis G : Interaction of liposome formulations with human skin in vitro. Int J Pharmacol 229:117-129, 2001.

13.

Rades T , Gerke A , Schütze W , et al : Characterization of a commercial liposome spray. Pharmazie 52:44-50, 1997.

14.

Artmann CW , Fassihi A , Kroling P , et al : Vehikelabhängige Mikrozirkulation der haut. Verbesserte bioverfugbarkweit am Beispiel von heparin liposomales spruhgel versus konventionelle heparin-gele. Zeitschrift für Allgemeinmedizin 73:242-244, 247-248, 1997.

15.

Artmann CW , Kroelling P , Regenold J , et al : Liposo-males spruehgel. Zeitschrift für Allgemeinmedizin 71:655, 1995.

16.

De Sanctis MT , Ceasarone MR , Incandela L , et al : Treatment of superficial vein thrombosis with standardized application of Essaven gel. A placebo-controlled, randomized study. Angiology 52(suppl 3):S57-S62, 2001.

17.

Titon JP , Auger D , Grange P , et al : Therapeutic management of superficial venous thrombosis with calcium nadroparin. Dosage testing and comparison with a non-steroidal anti-inflammatory agent. Ann Cardiol Angiol 43:160-166, 1994.

18.

Decousus H : Treatment of superficial-vein thrombosis: A randomized double-blind comparison of low-molecular-weight heparin, non-steroidal anti-inflammatory agent and placebo (abstract). Thromb Haemost 163:1657-1663, 2003.

19.

Jorgensen JO , Hanel KC , Morgan AM , et al : The incidence of deep venous thrombosis in patients with superficial thrombophlebitis of the lower limbs J Vasc Surg 18:70-73, 1993.

20.

Spahn G : Compliance with self-administration of heparin injections as outpatients. Eur J Trauma 28:104-109, 2002.