Comparative short-term effects of topical piroxicam gel, diclofenac gel, and EMLA cream on pain reduction during intravenous cannulation: A randomized clinical trial

Background: Intravenous (IV) cannulation is a common invasive procedure associated with pain and discomfort. This study compared the short-term effects of topical Piroxicam gel, Diclofenac gel, and EMLA cream on pain during IV cannulation. Methods: This participant- and outcome assessor-blinded randomized clinical trial included 123 hospitalized patients randomly allocated to three equal groups receiving topical Diclofenac gel, Piroxicam gel, or EMLA cream ( n = 41/group). Pain intensity was assessed using the Visual Analogue Scale immediately after cannulation and at 5, 10, 15, 30, and 45 min. Data were analyzed using linear mixed-effects models, with Kruskal–Wallis/Dunn and Friedman tests performed as sensitivity analyses. Categorical variables were analyzed using Chi-square or Fisher’s exact tests. Results: Baseline characteristics were comparable among groups (all p > .05). The linear mixed-effects model showed significant effects of treatment group ( p = .002), time ( p < .001), and treatment-by-time interaction ( p < .001). Bonferroni-adjusted pairwise comparisons showed lower pain intensity in the Diclofenac and EMLA groups than in the Piroxicam group immediately after cannulation and at 5 min; no significant pairwise differences were observed from 10 to 45 min. Sensitivity analyses supported the overall temporal decline in pain but showed some differences in individual pairwise comparisons. No serious adverse events were reported. Conclusion: Pain intensity declined substantially over time in all groups. In the primary analysis, Diclofenac and EMLA were associated with lower early pain intensity than Piroxicam, although some pairwise findings were sensitive to the analytical approach. Because no placebo control was included, findings should be interpreted as relative rather than absolute treatment effects. Trial registration: The trial was prospectively registered with the Iranian Registry of Clinical Trials (IRCT) under registration number IRCT20180107038251N8 on June 12, 2023 (1402/03/22), prior to the initiation of participant recruitment in October 2025. Available at: https://www.irct.ir/search/result?query=IRCT20180107038251N8