Clinical Studies with Reparil
Efficacy and safety of Aescin plus Diethylamine salicylate combination gel..., Efficacy and Tolerability of Escin / Diethylamine Salicylate Combination Gels.., Escin / diethylammonium salicylate / heparin combination gels...
Efficacy and safety of Aescin plus Diethylamine salicylate combination gel in patients with sports impact injuries
DEUTSCHE ZEITSCHRIFT FÜR SPORTMEDIZIN Vol. 7/8 (1996) 47, pp. 423-430
H. Hess, W. Groher, P. Lenhart, A. Thiel, M. Bulitta, F. Ley
Keywords: Impact injuries, aescin plus DEAS treatment, controlled double-blind study, tenderness reaction.
Abstract: In this confirmatory, double-blind, tricentre, controlled clinical trial, 314 patients with sports impact injuries were randomly allocated to three parallel treatment groups: aescin plus DEAS (n=106), aescin alone (n=104) and DEAS alone (n=104). The follow-up time was 24 hours. 305 patients (97.1%) were assessed with regard to efficacy (per protocol population). Furthermore, all randomised and treated patients were assessed in the intention-to-treat analysis with regard to efficacy and safety.
Tenderness on pressure was measured at 0 (baseline), 1, 2, 3, 4, 6 and 24 hours after the injury. Tenderness was defined by the amount of pressure at the centre of injury, at which the first pain reaction was reported by the patient. A topical application of approximately 5 g gel was carried out at 0, 4 and 8 hours after the first measurement of tenderness.
The primary variable was the area under the curve (AUC) of tenderness values over six hours. The mean AUC differed significantly between the three treatment groups revealing a superior effect of the combination gel. The treatment effect recorded for the aescin and DEAS-treated patient groups was of no statistical or clinical significance.
The time required to reach the contralateral (uninjured) tenderness value at the uninjured side (recovery time) was regarded as a secondary effectiveness variable. Six hours after the initiation of treatment, 43 of the patients (42.2%) treated with the combination gel had recovered. In the two other treatment groups, only one patient each (1.0%) had recovered within six hours.
Furthermore, the severity of tenderness was measured with the aid of a visual analogue scale (VAS). In comparison to the monopreparations, the combination gel produced a faster reduction in pain.
The safety and tolerability of all trial drugs was good. No adverse events were observed in any of the 314 treated patients.
Efficacy and Tolerability of Escin / Diethylamine Salicylate Combination Gels in Patients wiht Blund Injuries of the Extremities
International Journal of Sports Medicine, Vol. 22 2001, 430-5
H. Pabst, B. Segesser, M. Bulitta, D. Wetzel, S. Bertram
Keywords: Bruises, strains, escin, heparin, Reparil, tenderness reaction
Abstract: 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.
Escin / diethylammonium salicylate / heparin combination gels for the topical treatment of acute impact injuries: a randomised, double-blind, placebo controlled, multicentre study
Br J Sports Med 2002; 36:183-188
D Wetzel, W Menke, R Dieter, V Smasal, B Giannetti, M Bulitta
Abstract: Objectives: To investigate the clinical efficacy and safety of escin-containing gels in the topical treatment of blunt impact injuries.
Methods: Competitors in soccer, handball, or karate competitions were enrolled within two hours of sustaining a strain, sprain, or contusion and treated three times with the trial gel within a period of eight hours. Patients were randomised to three parallel groups consisting of two active treatment gels, containing escin (1 % or 2%), 5% diethylammonium salicylate, and 5000 IU heparin, or placebo gel.
Tenderness produced by pressure was measured at 0 (baseline), 1, 2, 3, 4, 6, and 24 hours after enrolment (within two hours of the injury). Tenderness was defined as the amount of pressure (measured by a calibrated caliper at the centre of the injury) that first produced a pain reaction as reported by the patient.
Results: A total of 158 patients were enrolled; 156 were evaluated in the intention to treat analysis. The primary efficacy variable was the area under the curve for tenderness over a six hour period. The gel preparations containing 1 % and 2% escin were significantly more effective (a priori ordered hypotheses testing controlling the multiple a = 5% significance level) than placebo (p, = 0.0001 and p2 = 0.0002 respectively). The treatment effects were 5.7 kp h/cm2 (95% confidence interval (CI) 2.9 to 8.5) and 5.9 kilopond (kp) h/cm2 (95% CI 2.9 to 8.8) between 1 % escin and placebo and between 2% escin and placebo respectively. These results were supported by secondary efficacy variables. The time to reach the baseline contralateral tenderness value (resolution of pain) at the injured site was shorter in the treatment groups than in the placebo group (p<0.0001). Both active gel preparations produced more rapid pain relief than the placebo gel. No relevant differences were detected between the two active gels. The safety and tolerability of the escin-containing gels were excellent.
Conclusions: Escin/diethylammonium solicylate/heparin combination gel preparations are effective and safe for the treatment of blunt impact injuries.