Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain

R Andrew Moore; C Gay-Escoda; R Figueiredo; Z Tóth-Bagi; T Dietrich; S Milleri; D Torres-Lagares; C M Hill; A García-García; P Coulthard; A Wojtowicz; D Matenko; M Peñarrocha-Diago; S Cuadripani; B Pizà-Vallespir; C Guerrero-Bayón; M Bertolotti; M P Contini; S Scartoni; A Nizzardo; A Capriati; C A Maggi

doi:10.1186/s10194-015-0541-5

Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain

R Andrew Moore, C Gay-Escoda, R Figueiredo, Z Tóth-Bagi, T Dietrich, S Milleri, D Torres-Lagares, C M Hill, A García-García, P Coulthard, A Wojtowicz, D Matenko, M Peñarrocha-Diago, S Cuadripani, B Pizà-Vallespir, C Guerrero-Bayón, M Bertolotti, M P Contini, S Scartoni, A NizzardoA Capriati, C A Maggi

Dentistry

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27 Citations (Scopus)

Abstract

BACKGROUND: Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of dexketoprofen and tramadol is untested, but predicted to be highly effective.

METHODS: This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours.

RESULTS: 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72 %) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95 % confidence interval 1.3 to 2.1). Addition of tramadol to dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable.

CONCLUSIONS: Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae.

TRIAL REGISTRATION: EudraCT (2010-022798-32); Clinicaltrials.gov ( NCT01307020 ).

Original language	English
Article number	541
Journal	The Journal of Headache and Pain
Volume	16
Issue number	1
DOIs	https://doi.org/10.1186/s10194-015-0541-5
Publication status	Published - 27 Jun 2015

Keywords

Dexketoprofen
Tramadol
Combination analgesics
Postoperative pain
Third molar
Randomised controlled trial
Dose range

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Moore, R. A., Gay-Escoda, C., Figueiredo, R., Tóth-Bagi, Z., Dietrich, T., Milleri, S., Torres-Lagares, D., Hill, C. M., García-García, A., Coulthard, P., Wojtowicz, A., Matenko, D., Peñarrocha-Diago, M., Cuadripani, S., Pizà-Vallespir, B., Guerrero-Bayón, C., Bertolotti, M., Contini, M. P., Scartoni, S., ... Maggi, C. A. (2015). Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain. The Journal of Headache and Pain, 16(1), Article 541. https://doi.org/10.1186/s10194-015-0541-5

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title = "Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain",

abstract = "BACKGROUND: Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of dexketoprofen and tramadol is untested, but predicted to be highly effective.METHODS: This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours.RESULTS: 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72 %) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95 % confidence interval 1.3 to 2.1). Addition of tramadol to dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable.CONCLUSIONS: Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae.TRIAL REGISTRATION: EudraCT (2010-022798-32); Clinicaltrials.gov ( NCT01307020 ).",

keywords = "Dexketoprofen, Tramadol , Combination analgesics, Postoperative pain, Third molar, Randomised controlled trial, Dose range",

author = "Moore, {R Andrew} and C Gay-Escoda and R Figueiredo and Z T{\'o}th-Bagi and T Dietrich and S Milleri and D Torres-Lagares and Hill, {C M} and A Garc{\'i}a-Garc{\'i}a and P Coulthard and A Wojtowicz and D Matenko and M Pe{\~n}arrocha-Diago and S Cuadripani and B Piz{\`a}-Vallespir and C Guerrero-Bay{\'o}n and M Bertolotti and Contini, {M P} and S Scartoni and A Nizzardo and A Capriati and Maggi, {C A}",

year = "2015",

month = jun,

day = "27",

doi = "10.1186/s10194-015-0541-5",

language = "English",

volume = "16",

journal = "The Journal of Headache and Pain",

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Moore, RA, Gay-Escoda, C, Figueiredo, R, Tóth-Bagi, Z, Dietrich, T, Milleri, S, Torres-Lagares, D, Hill, CM, García-García, A, Coulthard, P, Wojtowicz, A, Matenko, D, Peñarrocha-Diago, M, Cuadripani, S, Pizà-Vallespir, B, Guerrero-Bayón, C, Bertolotti, M, Contini, MP, Scartoni, S, Nizzardo, A, Capriati, A & Maggi, CA 2015, 'Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain', The Journal of Headache and Pain, vol. 16, no. 1, 541. https://doi.org/10.1186/s10194-015-0541-5

TY - JOUR

T1 - Dexketoprofen/tramadol

T2 - randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain

AU - Moore, R Andrew

AU - Gay-Escoda, C

AU - Figueiredo, R

AU - Tóth-Bagi, Z

AU - Dietrich, T

AU - Milleri, S

AU - Torres-Lagares, D

AU - Hill, C M

AU - García-García, A

AU - Coulthard, P

AU - Wojtowicz, A

AU - Matenko, D

AU - Peñarrocha-Diago, M

AU - Cuadripani, S

AU - Pizà-Vallespir, B

AU - Guerrero-Bayón, C

AU - Bertolotti, M

AU - Contini, M P

AU - Scartoni, S

AU - Nizzardo, A

AU - Capriati, A

AU - Maggi, C A

PY - 2015/6/27

Y1 - 2015/6/27

N2 - BACKGROUND: Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of dexketoprofen and tramadol is untested, but predicted to be highly effective.METHODS: This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours.RESULTS: 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72 %) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95 % confidence interval 1.3 to 2.1). Addition of tramadol to dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable.CONCLUSIONS: Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae.TRIAL REGISTRATION: EudraCT (2010-022798-32); Clinicaltrials.gov ( NCT01307020 ).

AB - BACKGROUND: Combination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of dexketoprofen and tramadol is untested, but predicted to be highly effective.METHODS: This was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours.RESULTS: 606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72 %) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95 % confidence interval 1.3 to 2.1). Addition of tramadol to dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable.CONCLUSIONS: Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae.TRIAL REGISTRATION: EudraCT (2010-022798-32); Clinicaltrials.gov ( NCT01307020 ).

KW - Dexketoprofen

KW - Tramadol

KW - Combination analgesics

KW - Postoperative pain

KW - Third molar

KW - Randomised controlled trial

KW - Dose range

U2 - 10.1186/s10194-015-0541-5

DO - 10.1186/s10194-015-0541-5

M3 - Article

C2 - 26123824

SN - 1129-2377

VL - 16

JO - The Journal of Headache and Pain

JF - The Journal of Headache and Pain

IS - 1

M1 - 541

ER -

Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain

Abstract

Keywords

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