Postgrad Med J: first published as 10.1136/pgmj.58.682.489 on 1 August 1982. Downloaded from Postgraduate Medical Journal (August 1982) 58, 489-492 Assessment of analgesic drugs in soft tissue injuries presenting to an accident and emergency department-a comparison of antrafenine, paracetamol and placebo C. DE GARA M. TAYLOR M.B., B.S., F.R.C.S. (Edin.) M.B., B.S. A. HEDGES Ph.D. Accident and Emergency Department, and Department of Clinical Pharmacology, St Bartholomew's Hospital, London ECIA 7BE Summary total hysterectomy and the second part was carried In a preliminary dose-finding study in patients follow- out in out-patients, admitted to the hospital Accident ing abdominal hysterectomy, antrafenine was found and Emergency department. to be an effective analgesic in single oral doses of 300-600 mg. First study-to establish an effective analgesic dose A double-blind controlled between-patient study for antrafenine was carried out to compare antrafenine (up to 1200 by copyright. mg daily), paracetamol (up to 4 g daily) and placebo Materials and methods as analgesic in the control of pain produced by Twenty-two female patients who had undergone ligamentous knee or ankle injuries, low back pain or total hysterectomy in the preceding 72 hr volunteered rib injuries. The only significant difference (P<0505) to participate in this part of the study. After narcotic noted between drug treatments was a longer duration intramuscular analgesics were discontinued, each of analgesic activity following antrafenine. patient was given a single dose of antrafenine as the The implications of these results for the study of first dose of oral analgesic medication in the post- potential analgesic drugs in soft tissue injuries are discussed. operative period. The doses of antrafenine used were 150 mg, 300 http://pmj.bmj.com/ mg, 450 mg and 600 mg; it was planned to administer Introduction each dose to 5 patients. The strength of the antra- Antrafenine, an ester derivative ofanthranilic acid, fenine used was 150 mg and to ensure controlled is a non-narcotic analgesic agent. Pharmacological conditions matching placebo tablets were used so studies have demonstrated analgesic and some anti- that each dose of test analgesic consisted of four inflammatory activity; the activity is associated with identical tablets. inhibition of and has been Each analgesic dose was given to all patients at the prostaglandin synthesis on September 26, 2021 by guest. Protected confirmed in controlled clinical studies (Berry et al., same time of day and assessment of pain relief was 1980; Manoury et al., 1979; Wisanto et al., 1981). The made hourly for 3 hr following the dose and finally faecal blood loss after antrafenine 450 mg/day or 900 when another dose of oral analgesic was requested. mg/day was similar to that after placebo and Pain relief was estimated by the patients using visual significantly less than after aspirin 1-8 g/day (Bown analogue scales, and the investigator assessed pain et al, 1980). relief by direct question using a pain score (Hedges et This clinical trial, which was carried out in two al., 1977). separate parts, was designed first to establish an effective analgesic dose for antrafenine, and then to compare the efficacy ofantrafenine, paracetamol and Results placebo in the relief of pain following soft tissue In total, 22 patients were involved in the study- 3 injury. patients at 150 mg dose, 6 patients at 300 mg dose, 7 The first part ofthe study was carried out in female patients at 450 mg dose and 6 patients at 600 mg patients admitted to St Bartholomew's Hospital for dose. A satisfactory analgesic effect was demon- 0032-5473/82/0800-0489 $02.00 © 1982 The Fellowship of Postgraduate Medicine Postgrad Med J: first published as 10.1136/pgmj.58.682.489 on 1 August 1982. Downloaded from 490 C. de Gara, M. Taylor and A. Hedges strated in all patients taking 300 mg, 450 mg and 600 groups, i.e. antrafenine, paracetamol or placebo, mg. The pain analogue results are shown in Fig. 1. according to a randomization sequence. Antrafenine at all dose levels was well tolerated; any Each patient was given a bottle containing 80 side effects noted were mild. tablets of either antrafenine, paracetamol or placebo 70 and a record card to note daily pain intensity, pain relief and number of tablets taken (Fig. 2). 60 : /.I5Omg(n=3) +300mg(n=6) E^> 50 Ail o 600mg(n=6 Day 0 ~~~~~~~~~~~~450mg (n=7) 40 1) Did the tablets help you? g yes 2 no > 30 2) How bad was your pain today? 20 No pain The most at all pain ever experienced 10 3) How much did the tablets help your pain? Helped Did not 0 2 3 6 8 a lot help Time (hr) 4) How many tablets have you taken today? m FIG. 1. Visual analogue scores at various times after administration of single oral doses ofantrafenine 150 mg, 300 mg, 450 mg or 600 mg 5) Have you taken tablets today: to patients who had undergone hysterectomy operations. The (Please tick correct box) number of patients in each group is shown in brackets. Visual Once analogue scale: 0, no pain at all; 100, the most pain ever experienced. Twice _ Three times by copyright. Four times Second study-comparison of antrafenine, paraceta- More than four times? _ mol and placebo 6) How soon did the pain return? (Please tick correct box) Following the initial study in post hysterectomy Pain was not helped pain, it was decided to investigate further the efficacy Less than one hour I of antrafenine in a comparative study in patients with One to two hours Two to three hours soft tissue injury. All patients entered in this part of Three to four hours _ the study were out-patients attending the Accident More than four hours? _ and Emergency Department at St Bartholomew's FIG 2. An example of the daily record card the http://pmj.bmj.com/ Hospital. It was considered that this study would patients were asked to complete. permit evaluation ofthis method ofscreening analge- sic drugs in a casualty department. The approval of The patients were asked to complete the booklet at St Bartholomew's Hospital ethical committee was the end of each day answering the questions: obtained to carry out this study. 'Did the tablets help you?' 'How many tablets did you have to take?' 'How often did you have to take the Materials and methods tablets?' on September 26, 2021 by guest. Protected 'How soon did the pain return?' The patients admitted to the second part of this They were asked to complete an analogue rating study were treated for ligamentous knee or ankle scale by marking a cross on a 10 cm line in answer to injury, low back pain or rib injury. Absence of bone the questions: injury was determined by X-ray and confirmed by 'How bad was your pain today?' the radiology registrar. All patients entered the study 'How much did the tablets help your pain?' voluntarily and written informed consent was ob- Careful instruction was given to all patients on tained. We excluded patients with a history of acute dosage and how to complete the pain relief scores or chronic hepatic insufficiency, mental retardation, and analogue scales. After 10 days the patients were pregnancy, history of alcoholism or drug dependence asked to return and were examined by one ofthe two or long-term treatment with other analgesics. investigators (M.T. or C. de G.) who assessed the The study was carried out under double blind degree of improvement, noted any side effects and conditions using a random block design. Patients counted the number of tablets returned. were allocated into one of the three drug treatment Postgrad Med J: first published as 10.1136/pgmj.58.682.489 on 1 August 1982. Downloaded from Analgesic drugs in soft tissue injuries 491 Dosage used Results From the first study, it was considered that single Of the 166 patients who entered the study, it was doses of antrafenine 300 mg would be most satisfac- possible to evaluate results of only 91. Fifty-nine tory. A previous study in osteoarthritis (Berry et al., patients failed to return for follow up and their final 1980) has also demonstrated significant analgesic assessment was incomplete. Of the 107 patients who activity in daily divided doses of450 mg/day and 900 did complete the study, the results of 15 of these mg/day. patients could not be analysed because ofinadequate In this part of the study a flexible dosage was records. considered necessary in order that patients could take A summary of the number of patients in each their analgesic according to their individual needs. diagnosis category and the analgesic treatment ad- Also, to maintain double-blind conditions, a compar- ministered is given in Table 1. There was no ative analgesic agent had to be chosen which would significant difference in the homogeneity of the three be effective in this indication and could also be given drug treatment groups, comparing age, sex, initial in the same dosage regimen as antrafenine. Paraceta- pain intensity or distribution of diagnosis. mol was considered to be such a suitable analgesic and patients were instructed to take one or two tablets every 4-6 hr, to a maximum of 8 tablets per TABLE 1. Diagnosis and analgesic treatment (number of patients) day, e.g. for antrafenine: 150-300 mg 4-6 hourly as Antrafenine Paracetamol Placebo Total required. Sprained ankle 15 16 17 48 for paracetamol: 500-1000 mg 4-6 hourly as Low back pain 4 11 10 25 required.