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 Cartilage. 2017 Dec;25(12):1942-1951. doi: 10.1016/j.joca.2017.09.002. Epub 2017 Sep 9.

Abstract

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.

Keywords: Arthralgia; Ibuprofen; Joint pain; Knee; Osteoarthritis; Symptom flare-up.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Arthralgia / drug therapy*
  • Capsules
  • Double-Blind Method
  • Equivalence Trials as Topic
  • Female
  • Gastrointestinal Diseases / chemically induced*
  • Headache / chemically induced
  • Humans
  • Hypertension / chemically induced
  • Ibuprofen / administration & dosage*
  • Knee Joint*
  • Lipids*
  • Male
  • Middle Aged
  • Pain Measurement
  • Symptom Flare Up
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Capsules
  • Lipids
  • Ibuprofen

Associated data

  • EudraCT/2014-004254-33