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 9.1 (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.