Tramadol/dexketoprofen (TRAM/DKP) compared with tramadol/paracetamol in moderate to severe acute pain: results of a randomised, double-blind, placebo and active-controlled, parallel group trial in the impacted third molar extraction pain model (DAVID study).
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ABSTRACT: OBJECTIVES:To compare efficacy/safety of oral tramadol 75?mg/dexketoprofen 25?mg (TRAM/DKP) and TRAM 75?mg/paracetamol 650?mg (TRAM/paracetamol) in moderate to severe pain following surgical removal of impacted lower third molar. DESIGN:Multicentre, randomised, double-blind, placebo-controlled, phase IIIb study. PARTICIPANTS:Healthy adult patients scheduled for surgical extraction of at least one fully/partially impacted lower third molar requiring bone manipulation. 654 patients were randomised and 653 were eligible for analysis. INTERVENTIONS:Surgery was performed under local anaesthetic. No sedation was permitted. Patients rated pain intensity (PI) using an 11-Numerical Rating Scale (NRS) (0 no pain; 10 worst pain). Participants experiencing moderate/severe pain (?4) within 4?hours of surgery were randomised (2:2:1 ratio) to a single oral dose of TRAM/DKP 75/25?mg, TRAM/paracetamol 75/650?mg or placebo. MAIN OUTCOME MEASURES:Efficacy was based patients' electronic diaries. Analgesia and pain were recorded as follows: pain relief (PAR) on a 5-point Verbal Rating Scale (0='no relief', 1='a little (perceptible) relief', 2='some (meaningful) relief', 3='lot of relief', 4='complete relief') at the predefined postdose time points t15 min, t30 min, t1 hour, t1.5 hour, t2 hour, t4 hour, t6 hour and t8 hour and PI on the 11-point NRS at t0 and at the same predefined postdose time points. Onset of analgesia documented using double stopwatch method over a 2-hour period. Primary endpoint was total pain relief over 6?hours (TOTPAR6). Rescue medication was available during the treatment period. RESULTS:TRAM/DKP was superior to TRAM/paracetamol and placebo at the primary endpoint TOTPAR6 (p<0.0001). Mean (SD) TOTPAR6 in the TRAM/DKP group was 13 (6.97), while those in the active control and placebo groups were 9.2 (7.65) and 1.9 (3.89), respectively. Superiority of TRAM/DKP over active comparator and placebo was observed at all secondary endpoints. Incidence of adverse events was comparable between active groups. CONCLUSIONS:TRAM/DKP (75/25?mg) is effective and superior to TRAM/paracetamol (75/650?mg) in relieving moderate to severe acute pain following surgical removal of impacted lower third molar, with a faster onset of action, greater and durable analgesia, together with a favourable safety profile. TRIAL REGISTRATION NUMBER:EudraCT 2015-004152-22 and NCT02777970.
SUBMITTER: Gay-Escoda C
PROVIDER: S-EPMC6377526 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
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