Objective: To investigate short-term efficacy and safety of a novel lipid ibuprofen formulation 1200 mg/day compared with standard ibuprofen 1200 mg/day and 2400 mg/day in episodic knee arthralgia/flaring pain. Design: Multicentre, randomised, double-blind, 3-arm, non-inferiority trial conducted at 27 primary care centres. Adults with ≥1 knee flare episode within 12 months were recruited within 24 h of new flare with pain severity ≥5 on a 0-10 numerical rating scale (NRS). Primary outcome was change from baseline in WOMAC pain subscale over 5 days. Main secondary outcome was Gastrointestinal Symptom Rating Scale (GSRS) change from baseline. Other endpoints included assessment of WOMAC total subscale scores and self-reported NRS for pain, subject nominated activity, stiffness and swelling. Results: 462 patients were enrolled (58.9% males; mean age 52.2 years). Treatment allocation comprised 148 lipid 1200 mg, 155 soft-gel 1200 mg, 159 soft-gel 2400 mg. WOMAC pain subscale scores decreased in all groups, with lipid 1200 mg being non-inferior to soft-gel 1200 mg (adjusted mean difference -0.26 [95% confidence interval [CI] -0.69, 0.17]) and to soft-gel 2400 mg (difference 0.19 [95% CI -0.24, 0.62]). No differences were seen in mean GSRS total scores. NRS secondary endpoints suggested greater improvements in the lipid 1200 mg group compared to soft-gel 1200 mg, with similar results to soft-gel 2400 mg. The most frequent drug-related adverse events (AEs) were gastrointestinal (GI) disorders, with statistically fewer events for lipid 1200 mg vs soft-gel 2400 mg (P = 0.01, post-hoc analysis). Conclusions: Ibuprofen 1200 mg/day lipid formulation was non-inferior to standard ibuprofen soft-gel capsules 1200 mg and 2400 mg/day in relieving flaring knee pain. NRS endpoints showed lipid 1200 mg was numerically similar to soft-gel 2400 mg. Trial registration number: EudraCT number: 2014-004254-33.

Additional Metadata
Keywords Arthralgia, Ibuprofen, Joint pain, Knee, Osteoarthritis, Symptom flare-up
Persistent URL dx.doi.org/10.1016/j.joca.2017.09.002, hdl.handle.net/1765/102254
Journal Osteoarthritis and Cartilage
Bierma-Zeinstra, S.M, Brew, J. (J.), Stoner, K. (K.), Wilson, R. (R.), Kilbourn, A. (A.), & Conaghan, P.G. (P. G.). (2017). A new lipid formulation of low dose ibuprofen shows non-inferiority to high dose standard ibuprofen: The FLARE study (flaring arthralgia relief evaluation in episodic flaring knee pain) - a randomised double-blind study. Osteoarthritis and Cartilage. doi:10.1016/j.joca.2017.09.002