Clinical trial NCT01902134: Oral Treatment for Orthopaedic 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 After Elective Unilateral Total Hip Arthroplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Pain
Keywords: Moderate to severe acute pain
Postoperative pain
Hip arthroplasty
Analgesics
Dexketoprofen
Tramadol
Lead sponsor: Menarini Group
Sponsor class: INDUSTRY
First posted: 2013-07-18
Enrollment: 641
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
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 male and female patients presenting moderate to severe pain after an elective primary hip arthroplasty 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:

* Male or female patients aged 18 to 80 years. Females participating in the study must be either of non-childbearing potential, or willing to use a highly effective contraceptive method.
* Scheduled to undergo standard primary (first-time) one-sided total hip replacement surgery due to primary osteoarthritis.
* 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.
* Pregnant and 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: SPID48 (Sum of Pain Intensity Differences Over First 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
measure: Percentage of Responders According to 50% Max TOTPAR (Total Pain Relief)
timeFrame: over 8 hours after the first dose
Other outcomes:
Locations:
city: Brno
country: Czech Republic
facility: Fakultni nemocnice Brno
city: Brno
country: Czech Republic
facility: Urazova nemocnice v Brne
city: Jihlava
country: Czech Republic
facility: Nemocnice Jihlava, p.o.
city: Kladno
country: Czech Republic
facility: Oblastni nemocnice Kladno
city: Mlada Boleslav
country: Czech Republic
facility: Oblastni nemocnice Mlada Boleslav a.s.
city: Frankfurt am Main
country: Germany
facility: Klinikum Frankfurt Höchst GmbH
city: Budapest
country: Hungary
facility: Uzsoki Hospital, Department of Orthopaedics
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Pécs
country: Hungary
facility: PTE KK Trauma Központ-Balesetsebészeti és Kézsebésze
city: Szolnok
country: Hungary
facility: MÁV Kórház és Rendelőintézet, Ortopédiai osztály
city: Székesfehérvár
country: Hungary
facility: Fejér Megyei Szent György Kórház
city: Liepaja
country: Latvia
facility: Liepaja Regional Hospital
city: Riga
country: Latvia
facility: Riga's 2nd Hospital
city: Riga
country: Latvia
facility: Hospital of Traumatology and Orthopaedics
city: Valmiera
country: Latvia
facility: Vidzemes Hospital
city: Kaunas
country: Lithuania
facility: Kaunas Clinical Hospital
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kaunas
city: Klaipeda
country: Lithuania
facility: Klaipedos Universitetine ligonine
city: Vilnius
country: Lithuania
facility: Respublikine Vilniaus universitetine ligonine
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Klioniczny w Bialymstoku
city: Elblag
country: Poland
facility: Warminskie Centrum Ortopedyczne
city: Lublin
country: Poland
facility: Wojewodzki Szpital Specjalistyczny
city: Tarnow
country: Poland
facility: Specjalistyczny Szpital im. E. Szczeklika
city: Wroclaw
country: Poland
facility: Urazowo - Ortopedycznej Wojewodzkiego Szpitala Specjalistycznego we Wrocławiu
city: Lodz
country: Poland
facility: Medical University of Lodz
state: Łódzkie
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Institute for orthopedic Surgery Banjica [Ortopedic Surgery
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
city: Nis
country: Serbia
facility: Clinic for Orthopedic Surgery and Trauma Bul. Dr Zorana Djindjica
city: Barcelona
country: Spain
facility: Hospital L'Esperança. Parc de Salut Mar.
city: Cadiz
country: Spain
facility: Hospital Universitario Puerta del Mar
city: Taichung
country: Taiwan
facility: China Medical University Hospital [Orthopedic]
city: Taichung
country: Taiwan
facility: Kuang Tien General Hospital
city: Cherkasy
country: Ukraine
facility: Cherkaska oblasna likarnia
city: Kharkiv
country: Ukraine
facility: Instytut patologii khrebta ta suglobiv im. prof. M.I. Sytenka NAMN Ukraine
city: Kyiv
country: Ukraine
facility: Kyivska oblasna klinichna likarnia
city: Sevastopol
country: Ukraine
facility: Sevastopolska miska likarnia №9
Study officials:
affiliation: Pain Research & Nuffield Department of Anaesthetics - University of Oxford
name: Andrew Moore, Professor
role: STUDY_CHAIR
affiliation: Balliol College Oxford
name: Henry J McQuay, Professor
role: STUDY_CHAIR
References:
citation: McQuay HJ, Moore RA, Berta A, Gainutdinovs O, Fulesdi B, Porvaneckas N, Petronis S, Mitkovic M, Bucsi L, Samson L, Zegunis V, Ankin ML, Bertolotti M, Piza-Vallespir B, Cuadripani S, Contini MP, Nizzardo A. Randomized clinical trial of dexketoprofen/tramadol 25 mg/75 mg in moderate-to-severe pain after total hip arthroplasty. Br J Anaesth. 2016 Feb;116(2):269-76. doi: 10.1093/bja/aev457.