Subcutaneous Injection of Diclofenac for the Treatment of Pain Following Minor Orthopedic Surgery ( DIRECT study): A Randomized Trial

OBJECTIVES: Parenteral diclofenac is frequently used for analgesia following minor orthopedic interventions. Currently available diclofenac formulations are for intramuscular (IM) or intravenous injection. A new 1 mL volume formulation of diclofenac containing hydroxypropyl-β-cyclodextrin (HPβCD) allows both SC and IM administration. The objective of this open-label, randomized, parallel group, active-controlled study was to assess the safety and efficacy of 75 mg diclofenac HPβCD, administered SC or IM, compared with IM Voltaren® 75 mg in inpatients undergoing minor orthopedic surgeries with moderate-to-severe postoperative pain. METHODS: A total of 325 patients were randomized to treatment. Surgery-related pain was comparable between groups before treatment and rapidly declined in all patients following diclofenac injection. The primary endpoint was investigator-assessed local tolerability up to 18 hours postinjection (redness, swelling, and hardening at the injection site each scored on a 4-point scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe). RESULTS: Local tolerability was found to be optimal for all the injected formulations, with mean overall scores (0 to 9) of 0.57, 0.31, and 0.26, for diclofenac HPβCD SC, diclofenac HPβCD IM, and Voltaren® IM, respectively. Consistently, the overall tolerability as judged by the patients and investigators was reported as good or excellent in more than 90% of cases in all groups. CONCLUSIONS: Overall, the study results indicate that safety and efficacy were similar irrespective of the diclofenac formulation used; thus, the new SC diclofenac HPβCD has an acceptable tolerability profile and may be considered a valid alternative to IM-delivered diclofenac formulations.