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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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). / Gay-Escoda, Cosme; Hanna, Magdi; Montero, Antonio; Dietrich, Thomas; Milleri, Stefano; Giergiel, Ewa; Bagi Zoltán, Tóth; Varrassi, Giustino.

In: BMJ open, Vol. 9, No. 2, e023715, 06.02.2019.

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@article{926a2463d76949168b66ee544aa23591,
title = "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)",
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{\textquoteright} electronic diaries. Analgesia and pain were recorded as follows: pain relief (PAR) on a 5-point Verbal Rating Scale (0={\textquoteleft}no relief{\textquoteright}, 1={\textquoteleft}a little (perceptible) relief{\textquoteright}, 2={\textquoteleft}some (meaningful) relief{\textquoteright}, 3={\textquoteleft}lot of relief{\textquoteright}, 4={\textquoteleft}complete relief{\textquoteright}) 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.",
keywords = "clinical trials, oral medicine, pain management, primary care, public health",
author = "Cosme Gay-Escoda and Magdi Hanna and Antonio Montero and Thomas Dietrich and Stefano Milleri and Ewa Giergiel and {Bagi Zolt{\'a}n}, T{\'o}th and Giustino Varrassi",
note = "Gay-Escoda C, Hanna M, Montero A, et al 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) BMJ Open 2019;9:bmjopen-2018-023715. doi: 10.1136/bmjopen-2018-023715",
year = "2019",
month = feb,
day = "6",
doi = "10.1136/bmjopen-2018-023715",
language = "English",
volume = "9",
journal = "BMJ open",
issn = "2044-6055",
publisher = "BMJ Publishing Group",
number = "2",

}

RIS

TY - JOUR

T1 - Tramadol/dexketoprofen (TRAM/DKP) compared with tramadol/paracetamol in moderate to severe acute pain

T2 - results of a randomised, double-blind, placebo and active-controlled, parallel group trial in the impacted third molar extraction pain model (DAVID study)

AU - Gay-Escoda, Cosme

AU - Hanna, Magdi

AU - Montero, Antonio

AU - Dietrich, Thomas

AU - Milleri, Stefano

AU - Giergiel, Ewa

AU - Bagi Zoltán, Tóth

AU - Varrassi, Giustino

N1 - Gay-Escoda C, Hanna M, Montero A, et al 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) BMJ Open 2019;9:bmjopen-2018-023715. doi: 10.1136/bmjopen-2018-023715

PY - 2019/2/6

Y1 - 2019/2/6

N2 - 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.

AB - 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.

KW - clinical trials

KW - oral medicine

KW - pain management

KW - primary care

KW - public health

UR - http://www.scopus.com/inward/record.url?scp=85061301094&partnerID=8YFLogxK

U2 - 10.1136/bmjopen-2018-023715

DO - 10.1136/bmjopen-2018-023715

M3 - Article

VL - 9

JO - BMJ open

JF - BMJ open

SN - 2044-6055

IS - 2

M1 - e023715

ER -