Clinical trial NCT01904149: Oral Treatment for Gynaecological Post-operative Pain With Dexketoprofen Trometamol and Tramadol Hydrochloride
Official title: A Randomized, Double-blind, Placebo and Active-controlled, Parallel-group Study to Evaluate the Analgesic Efficacy and Safety of Dexketoprofen Trometamol and Tramadol Hydrochloride Oral Fixed Combination on Moderate to Severe Acute Pain Following Abdominal Hysterectomy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Pain
Keywords: Moderate to severe acute pain
Postoperative pain
Abdominal hysterectomy
Analgesics
Dexketoprofen
Tramadol
Lead sponsor: Menarini Group
Sponsor class: INDUSTRY
First posted: 2013-07-22
Enrollment: 606
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate the analgesic efficacy of single and repeated doses of fixed combination of dexketoprofen trometamol (DKP) and tramadol hydrochloride (TRAM) in comparison to the single agents (and placebo for the single dose phase only).

Approximately 600 female patients presenting moderate to severe pain after a total/subtotal abdominal hysterectomy are eligible to be randomised provided that they experience moderate to severe pain on the day after surgery.

Detailed description: In this clinical trial patients were randomized to the described 6 treatment arms, where each arm define the treatment to be received in the first single dose phase (lasting 8 hours after the 1st treatment intake) and in the subsequent multiple-dose phase (lasting from the second treatment intake up to the 8 hours after the last intake). Namely:

* DKP/TRAM followed by DKP/TRAM;
* DKP followed by DKP;
* TRAM followed by TRAM;
* placebo followed by DKP;
* placebo followed by TRAM;
* placebo followed by DKP/TRAM;

The analyses of endpoints pertinent to the single dose phase were performed combining all the 3 treatment arms including placebo into one group, which resulted in the following 4 analysis groups: DKP/TRAM, DEXKETOPROFEN, TRAMADOL, and Placebo.

The analysis of endpoints pertinent to the multiple dose phase were performed combining the treatment arms including the same active treatment, which resulted in the following 3 analysis groups: DKP/TRAM, DEXKETOPROFEN, and TRAMADOL.

Eligibility criteria: Inclusion Criteria:

* Female patients aged 18 to 75 years.
* Scheduled to undergo a total or subtotal abdominal hysterectomy (with or without salpingo-oophorectomy) for benign conditions.
* Patients experiencing pain at rest of at least moderate intensity the day after surgery.

Exclusion Criteria:

* Patients not suitable for study treatments and rescue medication (RM) or those for whom non-steroidal anti-inflammatory drugs (NSAIDs), opioids, acetyl salicylic acid, pyrazolones or pyrazolidines are contraindicated.
* Patients with clinically significant abnormalities in vital signs, safety laboratory tests and 12-lead ECG at screening.
* Patients with history of any illness or condition that might pose a risk to the patient or confound the efficacy and safety study results.
* Patients using and not suitable to withdraw analgesics other than those specified in the protocol.
* Patients using and not suitable for withdrawing any of the prohibited medication specified in the protocol.
* Breastfeeding women.

Primary outcomes:
measure: SPID8 (Sum of Pain Intensity Differences Over 8 Hours)
timeFrame: over 8 hours after the first dose
Secondary outcomes:
measure: Percentage of Responders According to 50% Max TOTPAR (Total Pain Relief)
timeFrame: over 8 hours after first dose
measure: SPID48 (Sum of Pain Intensity Differences Over 48 Hours of the Multiple-dose Phase)
timeFrame: over 48 hours of the multiple-dose phase
measure: Percentage of Responders According to PI-VAS (Pain Intensity - Visual Analogue Scale)
timeFrame: over 48 hours of the multiple-dose phase
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Bajcsy-Zsilinszky Kórház
city: Debrecen
country: Hungary
facility: University Hospital of Debrecen
city: Szentes
country: Hungary
facility: Dr. Bugyi István Kórház
city: Székesfehérvár
country: Hungary
facility: Fejér megyei Szent György Kórház
city: Riga
country: Latvia
facility: Juras Medicinas Centre
city: Riga
country: Latvia
facility: Riga East University Hospital Gynecology Clinic
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kaunas
city: Vilnius
country: Lithuania
facility: Vilniaus gimdymo namai
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1
state: Lubelskie
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
state: Lubelskie
city: Bialystok
country: Poland
facility: Prywatna Klinika Polozniczo-Ginekologiczna
city: Poznan
country: Poland
facility: Ginekologiczno-Polożniczy Szpital Kliniczny UM w Poznaniu
city: Przemyśl
country: Poland
facility: Wojewodzki Szpital
city: Tarnow
country: Poland
facility: Specjalistyczny Szpital im. E. Szczeklika
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny, Centralny Szpital Kliniczny Mini
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSW w Warszawie
city: Bucharest
country: Romania
facility: Institutul pentru Ocrotirea Mamei si Copilului (IOMC) "Prof. Dr. Alfred Rusescu"
city: Bucharest
country: Romania
facility: Genesys Fertility Center
city: Bucharest
country: Romania
facility: Spitalul Clinic "Dr. Ioan Cantacuzino" - Sectia Clinica Obstetrica Ginecologie II
city: Bucharest
country: Romania
facility: Spitalul Clinic "Dr. Ioan Cantacuzino" - Sectia Clinica Obstetrica Ginecologie I
city: Bucharest
country: Romania
facility: Spitalul Universitar de Urgenta Bucuresti
city: Bucuresti
country: Romania
facility: Spitalul Clinic de Urgenta "Sfantul Pantelimon"
city: Targu-Mures
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Targu Mures - Sectia Obstretica Ginecologie I
city: Moscow
country: Russian Federation
facility: Moscow Regional Research Institute of Obstetrics and Gynecol
city: Saint Petersburg
country: Russian Federation
facility: FGUZ Clinical Hospital 122 n.a. L.G. Sokolova FMBA
city: Sliac
country: Slovakia
facility: GYNPOR, s.r.o.
city: Ferrol
country: Spain
facility: Complejo Hospitalario Arquitecto Marcide
city: Lérida
country: Spain
facility: Hospital Universitario Arnau de Vilanova
Study officials:
affiliation: Balliol College Oxford
name: Henry J McQuay, Professor
role: STUDY_CHAIR
affiliation: Pain Research & Nuffield Department of Anaesthetics - University of Oxford
name: Andrew Moore, Professor
role: STUDY_CHAIR
References:
citation: Moore RA, McQuay HJ, Tomaszewski J, Raba G, Tutunaru D, Lietuviete N, Galad J, Hagymasy L, Melka D, Kotarski J, Rechberger T, Fulesdi B, Nizzardo A, Guerrero-Bayon C, Cuadripani S, Piza-Vallespir B, Bertolotti M. Dexketoprofen/tramadol 25 mg/75 mg: randomised double-blind trial in moderate-to-severe acute pain after abdominal hysterectomy. BMC Anesthesiol. 2016 Jan 22;16:9. doi: 10.1186/s12871-016-0174-5.