Comparison of two doses of ketoprofen to treat pain: a double‐blind, randomized, noninferiority trial

Abstract

The aim of our study was to compare the efficacy and safety of two doses of ketoprofen (200 mg vs. 300 mg/day) in ambulatory emergency patients with pain related to traumatic and nontraumatic bone and joint diseases. We tested the hypothesis that the efficacy of the lower dose was not lower than that of the higher dose in a double‐blind, randomized, noninferiority trial. Patients included in the study were aged 18–65 years with closed benign trauma of the motor system or acute noninfectious rheumatologic conditions, with a resting pain intensity ≥3/10 on a numeric pain scale (NPS), requiring ketoprofen for 5 days. The main end‐point was based on two efficacy co‐criteria: (i) mean change from baseline of resting pain intensity at the end of the day over 5 days and (ii) total intake of concomitant analgesics. We included 409 patients: 200 in the 200‐mg group and 209 in the 300‐mg group. The mean change in pain intensity at rest (difference between groups: 0.0, 95% CI −0.4 to 0.4; P = 1.00) and in analgesic consumption (difference between groups: −0.6, 95% CI −1.9 to 0.6; P = 0.33) was not significantly different between the two groups, and the differences were lower than the predefined inferiority margins (0.5 and 1.5, respectively), thus demonstrating noninferiority. No significant difference was noted in the incidence of adverse events (21% vs. 20%, P = 0.71). The efficacy of the 200‐mg daily dose of ketoprofen in relieving pain in emergency cases was not inferior to that of the 300‐mg dose.

How to deal with pain in the emergency department - pain management review

“…No significant differences in safety were also observed, however, 200 mg remains the preferred maximum daily dose. (18) Ketoprofen is used most often to treat pain resulting from trauma and acute rheumatic conditions. In such patients, ketoprofen is believed to have a better and faster analgesic effect and provide more relief than ibuprofen or diclofenac.…”

Treating sickle cell anaemia: the TWiTCH trial

“…The choice of the appropriate dose of NSAID is simple because there is a ceiling effect; lower doses are recognised to be as efficient as higher doses. 2 By contrast, opioids are associated with an enormous intraindividual variability due to numerous factors, including phenotypic and genotypic characteristics. 3 The consequence is that administration of a fi xed dose of morphine is inappropriate because it…”

“…Effective ongoing analgesia can be practically challenging to deliver in an emergency department (ED) with a diverse population and a high volume of patients being managed simultaneously. 2 Obvious problems with opioids are the need for multiple dosages to achieve the desired eff ect, clinically signifi cant dose-dependent side-eff ects, logistical delay involved in the administration and diffi culties in continuing titration (with storage of half-used syringes with narcotics), risk of misuse, and potential for tolerance at the community level. Added to the inevitable periods of pain experienced by patients while being managed with titrated doses of intravenous opioids, all these issues provide compelling reasons for why morphine should not be used as fi rst-line analgesia in acute pain management in a high-volume ED setting.…”

“…predictably favour the hydroxyurea group (anti-conservative) when used with a non-inferiority model. 2,3 A 24-month mean time-averaged TCD velocity estimation from a general linear mixed model using all TCD velocities captured throughout the trial was used, including velocities when patients were transfused during the 6-9-month overlap, or when rescue transfusions were used in case of low hydroxyurea response, which occurred in at least 32% of the patients. Also, patients had a mean age of 9•7 years at enrolment and long duration of past transfusions (4•5 years in the hydroxyurea group), so most patients might have not have been at risk at the time of enrolment.…”

Titrated doses are optimal for opioids in pain trials

“…The choice of the appropriate dose of NSAID is simple because there is a ceiling effect; lower doses are recognised to be as efficient as higher doses. 2 By contrast, opioids are associated with an enormous intraindividual variability due to numerous factors, including phenotypic and genotypic characteristics. 3 The consequence is that administration of a fi xed dose of morphine is inappropriate because it…”