Efficacy and Tolerability of Escin/Diethylamine Salicylate Combination Gels in Patients with Blunt Injuries of the Extremities

The aim of this confirmative, monocentre, double-blind, controlled clinical trial was to investigate whether different escin combinations show differences in comparison to placebo with regard to pain reactions in the topical treatment of sports injuries. A total of 126 patients with blunt injuries of the extremities were randomly allocated to four parallel groups: Reparil®-Gel N (n = 32), Reparil®-Gel (n = 31), Reparil®-Sportgel (n = 32) and a placebo gel (n = 31). All patients were evaluated for efficacy (intention to treat) and tolerability. A per-protocol analysis was also carried out, in which 12 of the 126 patients were excluded due to protocol violations. The intention-to-treat and per-protocol analyses produced similar results. The patients had suffered contusions while participating in soccer, hockey, karate, tae-kwon-do, handball, American football, rugby or tennis. The measured variable was the pressure required at the centre of the lesion to elicit the first pain reaction (tenderness reaction) at measuring time 0 (baseline) and then 1, 2, 3, 4, 6 and 24 h after the injury. The primary variable was the area under the curve (AUC) for tenderness over a six-hour period. The mean AUC differed significantly in the four groups (Kruskal-Wallis test p = 0.0001). Then six pairwise comparisons of two treatment groups each were carried out using the Mann-Whitney test. To control the multiple significance level of 5 %, the adjusted p-values according to the Holm-Shaffer method were used in these tests. The three active gels were significantly superior to the placebo gel (Mann-Whitney test, p = 0.0004 in each case) in terms of the AUC. There were no significant differences between the active test substances in terms of the primary variable. The intensity of the pain was also measured on a visual analogue scale (VAS). The pain diminished more rapidly with the Reparil gels than with the placebo. The tolerability of all test substances was good. No adverse events were observed in any of the 126 patients. Escin combination gels are more effective than a placebo and are also well tolerated. Therefore, they can be recommended for the treatment of blunt injuries caused during sports and leisure activities.

Key words:

Bruises, strains, sprains, escin, heparin, Reparil, tenderness reaction.

References

• 1 Alicicco E, Venerando A. Observations on the use of a form of drug treatment for minor trauma: a controlled study.  Clin Eur. 1981;  20 505-515
• 2 Anscombe F. Computing in statistical science through APL. New York; Springer-Verlag 1981: 426
• 3 Areh O MN. Preparation and pharmacological investigation of DEAS. Ph. D. thesis. Massachusetts; College of Pharmacy and Allied Health Services 1983
• 4 BAnA .Repräsentative Haushaltsbefragungen in den Jahren 1988 - 1992, 1996, 1997. Dortmund;
• 5 Böhmer D. Escin aus der Rosskastanie zur lokalen Therapie stumpfer Sportverletzungen.  Der Kassenarzt. 1992;  4 55-56
• 6 Bonnekoh A, Rost R, Völker K, Giannetti B M, Bulitta M, Ley F. Doppelblinde kontrollierte klinische Prüfung zum Vergleich der Wirksamkeit und Verträglichkeit eines Escin-Kombinationsgels mit Diclofenacdiethylaminsalz bei induziertem Unterspritzungshämatom.  Dt Zschr für Sportmedizin. 1992;  43 3-7
• 7 Calabrese C, Preston P. Report of the results of a double-blind, randomized, single-dose trial of a topical 2 % Escin gel versus placebo in the acute treatment of experimentally-induced hematoma in volunteers.  Planta Med. 1993;  59 394-397
• 8 Chen S C. Ankle injuries. In: Helal B, King J, Grange W (eds.) Sport injuries and their treatment. Chapman & Hall Ltd. 1986: 413-436
• 9 Crielaard J M, Franchimont P. Behandlung von Muskelverletzungen.  Therapiewoche. 1988;  38 2505-2509
• 10 Felix W, Schneider E. Vasoactive effects of Escin. . Athens/Greece; Intern. Congress of Angiology 1985; June 9 - 14
• 11 Gibaldi M, Perrier D. Pharmacokinetics. New York; Marcel Dekker Inc. 1982
• 12 Götz A K, Giannetti B M. Naturstoffe in der Therapie stumpfer Sportverletzungen - heute noch zeitgemäß?.  Erfahrungsheilkunde. 1990;  6 362-371
• 13 Hess H, Groher W, Lenhart P, Thiel A, Bulitta M, Ley F. Wirksamkeit und Verträglichkeit eines Kombinationsgels mit Escin und Diethylamin-salicylat bei Patienten mit stumpfen Verletzungen.  Dt Zschr für Sportmedizin. 1996;  47 423-430
• 14 . IDV< .N Handbuch. . Gauting/FRG; 1987 Version 2.2: 3-80
• 15 Lang W. Untersuchungen zur perkutanen Absorption von ³H-Escin bei Maus und Ratte.  Arzneim-Forsch. 1974;  24 71-76
• 16 Lang W. Studies on the percutaneous absorption of ³H-Escin in pigs.  Res Exp Med. 1977;  169 175-187
• 17 Lang W. Untersuchungen zur perkutanen Absorption von ³H-Escin und 14C Diethylammoniumsalicylat aus Reparil®-Gel an der Ratte. Unpublished Report. Cologne; Biol Inst MADAUS AG 1987
• 18 Mellerowicz H, Pfeifer G, Bulitta M, Ley F. Klinische Doppelblindstudie zum Vergleich der Wirksamkeit verschiedener Gelexterna beim Unterspritzungshämatom.  Prakt Sport-Traumatologie und Sportmedizin. 1994;  2 72-77
• 19 Preziosi P. Pharmacological report on Reparil® gel. University of Naples 1990, Febr. 20
• 20 Rothaar J, Thiel W. Percutaneous gel therapy of blunt sports injuries: a placebo-controlled, double-blind study.  Med Welt. 1982;  27 1006-1010
• 21 Rothkopf M, Vogel G. Further results on the efficacy and mode of action to the horse chestnut saponin Escin.  Arzneim-Forsch (Drug Res). 1976;  26 225
• 22 . SAS Institute Inc .SAS/STAT User’s guide. Cary, North Carolina; Vol. 1 & II, SAS/GRAPH Software, Vol. I & II, SAS/FSP 1990 Version 6 edition
• 23 Schneider P G. Klinisch-pharmakologische Bestimmung der Resorption von Escin nach topischer Applikation eines 2 %igen Escin-Gels. Unpublished Report. Cologne; MADAUS AG 1991
• 24 Shaffer J P. Modified sequentially rejective multiple test procedures.  J Am Statist Assoc. 1986;  81 826-831
• 25 Smith P K, Gleason H L, Stoll C G. Studies of the pharmacology of Salicylates.  J Pharmacol Exp Ther. 1946;  87 237-255

1 sulphated escin with heparinoid properties