Comparison of the efficacy and tolerance of isoxicam and piroxicam following surgery for skiing accidents

Transcription

1 Br. J. clin. Pharmac. (1986), 22, 161S-165S Comparison of the efficacy and tolerance of isoxicam and piroxicam following surgery for skiing accidents P. MASSART & 'H. BEZES Clinique Chirurgicale et Traumatologique de la Facultd de Medecine de Grenoble et 'Service d'urgence et de Traumatologie de l'h6pital Sud de Grenoble-Echirolles, F Echirolles, France 1 A 10 day double-blind study was carried out comparing isoxicam (300 mg day-') and piroxicam (40 mg day-' for the first two days and 20 mg day-' for the remaining days) following surgery in patients who had sustained skiing accidents. There were 20 patients in each group. The isoxicam-treated group had a slightly greater mean pain score prior to treatment. 2 Both isoxicam and piroxicam reduced pain and nocturnal awakening at days 5 and 10, but isoxicam was significantly superior to piroxicam in producing improvement in pain (at day 5, P < 0.05) and in nocturnal awakenings (at day 10, P < 0.05). 3 Both agents facilitated rehabilitation and there was no significant difference between them in this regard. 4 All patients in both groups considered themselves 'better' or 'much better' on day 5 of treatment. 5 Both agents were well tolerated by most patients but one patient in each group left the trial because of abdominal pain. One patient stopped isoxicam when she was found to be pregnant. Keywords isoxicam piroxicam surgery skiing rehabilitation Introduction Non-steroidal anti-inflammatory drugs (NSAIDs) have been employed for relief of pain and inflammation following trauma and orthopaedic surgical procedures. The present study was conducted between February and April, 1984, to compare the efficacy and tolerance of isoxicam and piroxicam, two NSAIDs having long half-lives, following surgery for trauma due to skiing accidents. Methods Forty patients admitted to the Emergency and Trauma Service of l'h6pital-sud de Grenoble- Echirolles following skiing accidents were entered into the study. All were operated upon either on the same day or during the days following admission. Postoperatively, patients were randomly assigned between two groups, one treated with isoxicam 300 mg day' and the other with piroxicam 40 mg day-' for the first 2 days and 20 mg day-' for the following days. The study was carried out in a double-blind fashion for 10 days. Patients were excluded from the study if they showed evidence of hepatic disease, active gastric or duodenal ulceration, or had a previous history of allergy to aspirin or another NSAID. In addition, individuals under 18 years of age and women of childbearing potential were excluded from the study. Correspondence: Pr H. Bezes, l'h6pital Sud de Grenoble-Echirolles, F Echirolles, France 161S

2 162S P. Massart & H. Bezes The study was carried out in compliance with the Declaration of Helsinki. During study additional analgesics including dextropropoxyphene and paracetamol were permitted when a pressing need occurred but all others NSAIDs were forbidden. Hypnotic drugs were not permitted unless the patient specifically asked for them. Anti-coagulants were prescribed as necessary, with close monitoring of haemostasis. When fit, patients commenced rehabilitation during the study. Assessment of efficacy Efficacy was judged on: a. Three subjective evaluations obtained by the investigator from the patient before treatment, in the middle of treatment (day 5) and at the end of treatment (day 10): 1. subjective evaluation of spontaneous pain assessed on a visual analogue scale of 100 mm (Huskisson, 1974); 2. frequency of nocturnal awakening due to pain as well as the need to resort to sleeping pills; and 3. ease of rehabilitation according to a fourpoint scoring system of 'easy, without pain', 'possible, with pain', 'difficult', and 'impossible'. b. Overall evaluation of the patient at days 5 and 10 compared to day 0 according to the assessments 'much better', 'better', 'slightly better', 'equivalent', 'slightly worse', 'worse', and 'much worse'. c. Global evaluation by the investigator at days 5 and 10 compared to day 0, according to the same ratings. Assessment of tolerance Patients' tolerance of treatment was evaluated at the last visit when the sole question asked was, 'How did you tolerate the treatment?' Adverse reactions were noted together with their date of occurrence, severity, evolution, and ascribability to treatment. Therapy could be interrupted either in the event of a serious complication in which case the reason for interruption had to be duly and precisely stated. Statistical analyses Student's t-test, a parametic test, was selected for comparing the variables sex, weight, height, and age at injury. Nonparametic tests were used for other values. The Mann-Whitney U test was used to compare the following variables: intensity of spontaneous pain as well as the percent improvement of this pain. The chi square test was used for the variables sex, presence or absence of pain, number of nocturnal awakenings, ease of rehabilitation, and assessments by patients and physician at days 5 and 10. Results Characteristics ofpatients (Table 1) No significant difference between the two groups of patients was shown as far as sex, age, weight, or height was concerned. The age of the injury was comparable in the two groups, with means of less than one day in both groups. The type of injury was comparable in the two groups (Table 2). All of the injured presented with a fracture of an upper or lower limb with the exception of one in the isoxicam group who had suffered a serious sprain of the knee. Withdrawals from the study The number of patients who withdrew from the trial was low and similar in the two populations. One of the 20 patients, in the isoxicam group had to be withdrawn from the trial because of con- Table 1 Patient characteristics (n=19) (n=20) Male Female 6 10 Mean age (years) 35 (19-64) 35 (18-56) Mean weight (kg) 66 (50-75) 62 (42-80) Mean height (cm) 167 ( ) 169 ( ) Age of injury (days)

3 and piroxicam following surgery 163S Table 2 Traumatic lesions present (n = 19) (n = 20) Fracture of tibia-fibula 8 12 clavicle 2 2 femur 4 1 tibial plateau 1 2 upper limb 2 1 foot 2 2 Knee sprain 0 1 firmed pregnancy, two patients had to stop treatment because of the appearance of abdominal pain, one before day 5 (isoxicam group) and one after day 5 (piroxicam group). One patient in the isoxicam group had nocturnal sweats of mild intensity and one patient in the piroxicam group had an epistaxis of light intensity. Both patients continued treatment to day 10. A valid result was obtained in 38 cases at day 5 (18 isoxicam, 20 piroxicam) and in 37 cases at day 10 (18 isoxicam, 19 piroxicam). Efficacy on spontaneous pain (Tables 3 and Figure 1) As expressed on the visual scale of Huskisson (1974), spontaneous pain was slightly greater at day 0 in the isoxicam group but the difference between the groups was not statistically significant. Pain was greatly decreased in the two groups at day 5, with a significant superiority for the isoxicam group. Pain remained greatly decreased to the end of the treatment period in both groups, but with a significant superiority for the isoxicam group. At day 5, seven patients out of 18 in the isoxicam group and two patients out of the 20 in the piroxicam group had no pain. This difference is statistically significant (P < 0.05). Efficacy on nocturnal awaking due to pain (Table 4) The two groups showed no difference before treatment. On the fifth day, no patient in the isoxicam group had 'frequent' nocturnal awakings whereas there were still four such patients in the piroxicam group. However, at the end of treatment the two agents proved equally effective on this parameter. Efficacy on ease of rehabilitation (Table 5) Both treatments were effective on this parameter and no significant difference existed between the two groups. Global assessment of patients at days 5 and 10 (end of treatment) (Table 6) By the fifth day, all patients judged their conditions to be 'better' or 'much better'. This result was confirmed at the end of the treatment (10 days). There was no significant difference between the two treatments. Physicians' assessments These conformed to those of the patients. Table 3 Pain intensity on analogue scale of 100 mm (Huskisson, 1974). treatment 5 10 treatment 5 10 Mean s.d Significance ** ** ** ** Wilcoxon test for paired series for internal changes in each group compared to the pain measured before treatment. (**P < 0.01).

4 164S P. Massart & H. Bezes 36i6 E E El 201 a. ci 10I*...a y.i"'i z :- -b*-it ~~~~~~~~~~~~~~~~~~W -' o..7'll- Diy 10: S W)- Table 4 Nocturnal awakenings assessed by the patients treatment S 10 treatment 5 10 Absent Rare Frequent Significance ** ** NS * *P < 0.05 chi square test **P < 0.01 chi square test NS not significant Table 5 Ease of rehabilitation treatment 5 10 treatment 5 10 Easy Possible Difficult Impossible Significance **** **** ****P< 0.001, chi square test verified by chi square test with regrouping of columns

5 Table 6 Global assesssment of patients in comparison with Day 0 and piroxicam following surgery DayS Day 10 DayS Day 10 n Much better Better Slightly better Equivalent Slightly worse Worse Much worse S Discussion Several other papers have been written about use of NSAIDs in acute injuries. Some of them relate to piroxicam (Filho, 1983; Sarwar, 1982) and others to isoxicam (Dumpert et al., 1983; Reyes et al., 1984). In addition comparisons have been made between oxicams and other NSAIDs in acute musculoskeletal disorders, e.g. naproxen sodium (Bouchier-Hayes, 1984), indomethacin (Commandre, 1983; Edwards, 1984; Gunther, 1979), ibuprofen and phenylbutazone (Nussdorf, 1977). However we are unaware of any comparisons between piroxicam and isoxicam in the treatment of acute sport injuries. When comparing pain scales at day 5 and day 10, between the two groups, no significant differences were seen, but the percentage improvements were significantly different (P < 0.05) as were the number of patients without any pain at day 5 (P < 0.05). Concerning nocturnal awakenings, there was a significant difference at day 5 for isoxicam which did not occur with piroxicam. was superior to piroxicam at day 10. We conclude that isoxicam and piroxicam are effective anti-inflammatory agents for posttraumatic pain since by day 5 all patients judged their conditions to be better or much better. We would suggest that 5 days' treatment may be sufficient for the majority. The percent of improvement of spontaneous pain at the fifth day of treatment was significantly more marked in the isoxicam group than in the piroxicam group. This difference was maintained to the end of the treatment period. Under treatment, the number of nocturnal awakings seemed to be less frequent in the isoxicam group than in the piroxicam group. We also noticed that all the studied criteria were clearly improved, that the assessment of the patient and of the physician was always favourable, and that the tolerance of the two products proved to be good. References Bouchier-Hayes, T. A. T. (1984). Naproxen sodium and piroxicam in acute musculo-skeletal disorders. Br. J. Sports Med., 18, Commandre, F. (1983). Double-blind comparative study of piroxicam and indomethacin in acute locomotor affections linked with sports. second symposium. Eur. J. Rheum. Inflamm., Dumpert, H. P. & Muller, M. (1983). The safety and efficacy of isoxicam in musculoskeletal disorders. Non steroidal anti-inflammatory agents in the elderly. Internation Drug Symposium, Paris, October 1983, ed. Amor, B. Edwards, V. (1984). A multicentre comparison of piroxicam and indomethacin in acute soft tissue sports injuries. J. Int. med. Res., 12, Filho, J. L. (1983). Multicenter study of piroxicam in the treatment of acute musculoskeletal diseases involving 3011 patients. second symposium. Eur. J. Rheum. Inflamm., Gunther, R. (1979). Efficacy and safety of piroxicam and indomethacin in the treatment of musculoskeletal disorders - a double blind comparative study. Z. Rheumatol., 38, Huskisson, E. C. (1974). Measurement of pain. Lancet, ii, Nussdorf, R. T. (1977). and acute musculoskeletal disease: a double-blind 14-day study comparing piroxicam and phenylbutazone. : Royal Society of Medicine Int. Congress Symposium Series No 1, pp Reyes, T. M., Reyes, 0. L., et Coll., (1984). Clinical evaluation of isoxicam in the treatment of acute musculoskeletal disorders. Phil. J. int. Med., 22, Sarwar, A. (1982). in the treatment of acute musculoskeletal disorders: Bangladesh multicentre study. Curr. Ther. Res., 32,