Tramadol/Dexketoprofen Analgesic Efficacy Compared with Tramadol/Paracetamol in Moderate to Severe Postoperative Acute Pain: Subgroup Analysis of a Randomized, Double-Blind, Parallel Group Trial-DAVID Study.

Introduction: Recently the DAVID study demonstrated the better analgesic efficacy of tramadol hydrochloride/dexketoprofen 75/25 mg (TRAM/DKP) over tramadol hydrochloride/paracetamol 75/650 mg (TRAM/paracetamol) in a model of moderate to severe acute pain following surgical removal of an impacted third molar. The aim of this subpopulation analysis was to gain a deeper understanding of the relationship between baseline pain intensity (PI) level and the effectiveness in pain control of the TRAM/DKP combination in comparison with the TRAM/paracetamol combination. This will further improve and facilitate the accurate design of future acute pain studies for the use of the TRAM/DKP combination.

Methods: Patients experiencing at least moderate pain, defined as a PI score ≥ 4 in an 11-point numerical rating scale (NRS) were stratified according to NRS-PI at baseline (NRS ≥ 4, 5, 6, 7, or 8) or aggregated in two groups: (i) moderate pain, NRS-PI ≥ 4 to ≤ 6; (ii) severe pain, NRS-PI > 6. Analgesic efficacy was assessed at pre-specified time points by using pain relief (PAR) on a 5-point verbal rating scale (VRS) and PI on an 11-point NRS. The primary endpoint was total PAR over 6 h post-dose (TOTPAR6); secondary endpoints included, among others, the time course of mean PAR and PI scores over 8 h, TOTPAR over 2, 4, and 8 h post-dose, and the sum of PI difference (SPID) over 2, 4, 6, and 8 h. Safety evaluation was based on the incidence, seriousness, intensity, and causal relationship of treatment-emergent adverse events (TEAEs).

Results: The analgesic efficacy evaluated by TOTPAR6 (primary endpoint) remained steady across increasing baseline PI-NRS cutoff groups with TRAM/DKP, but not with TRAM/paracetamol. The study also demonstrated the superiority of TRAM/DKP combination over TRAM/paracetamol in terms of TOTPAR over 2, 4, and 8 h post-dose and SPID at 2, 4, 6, and 8 h post-dose in both baseline PI groups (moderate or severe); similarly, the time course of PAR and PI indicated better efficacy with TRAM/DKP as soon as 30 min and up to 4-6 h. The incidence of adverse drug reactions was not increased in the severe baseline PI group.

Conclusion: Overall, the results of this subgroup analysis of the DAVID study confirmed the superiority of the analgesic efficacy of TRAM/DKP vs TRAM/paracetamol, irrespective of the baseline PI.