MedPath

Oral Treatment for Orthopaedic Post-operative Pain With Dexketoprofen Trometamol and Tramadol Hydrochloride

Phase 3
Completed
Conditions
Acute Pain
Interventions
Drug: Placebo
Drug: Dexketoprofen/Tramadol-single dose
Drug: Dexketoprofen-single dose
Drug: Tramadol-single dose
Drug: Dexketoprofen/Tramadol-multiple doses
Drug: Tramadol-multiple doses
Drug: Dexketoprofen-multiple doses
Registration Number
NCT01902134
Lead Sponsor
Menarini Group
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
641
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo followed by DKP/TRAMPlaceboPlacebo single dose followed by Dexketoprofen/Tramadol-multiple doses
DKP/TRAM followed by DKP/TRAMDexketoprofen/Tramadol-single doseDexketoprofen/Tramadol-single dose followed by Dexketoprofen/Tramadol-multiple doses
DKP/TRAM followed by DKP/TRAMDexketoprofen/Tramadol-multiple dosesDexketoprofen/Tramadol-single dose followed by Dexketoprofen/Tramadol-multiple doses
DKP followed by DKPDexketoprofen-single doseDexketoprofen-single dose followed by Dexketoprofen-multiple doses
TRAM followed by TRAMTramadol-multiple dosesTramadol-single dose followed by Tramadol-multiple doses
DKP followed by DKPDexketoprofen-multiple dosesDexketoprofen-single dose followed by Dexketoprofen-multiple doses
TRAM followed by TRAMTramadol-single doseTramadol-single dose followed by Tramadol-multiple doses
Placebo followed by DKP/TRAMDexketoprofen/Tramadol-multiple dosesPlacebo single dose followed by Dexketoprofen/Tramadol-multiple doses
Placebo followed by DKPPlaceboPlacebo single dose followed by Dexketoprofen-multiple doses
Placebo followed by DKPDexketoprofen-multiple dosesPlacebo single dose followed by Dexketoprofen-multiple doses
Placebo followed by TRAMPlaceboPlacebo single dose followed by Tramadol-multiple doses
Placebo followed by TRAMTramadol-multiple dosesPlacebo single dose followed by Tramadol-multiple doses
Primary Outcome Measures
NameTimeMethod
SPID8 (Sum of Pain Intensity Differences Over 8 Hours)over 8 hours after the first dose

Sum of Pain Intensity Differences calculated as the weighted sum of the PI-VAS differences over 8 hour period. PI-VAS corresponds to the pain intensity measured by a 0-100 visual analogue scale (0=no pain to 100=worst pain imaginable) which was measured at 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, and 8h after the first dose. A higher value in SPID indicates greater pain relief.

The analysis was performed combining all randomization arms including placebo into one group, which resulted in the following 4 analysis groups: DKP/TRAM, DEXKETOPROFEN, TRAMADOL, and Placebo.

Secondary Outcome Measures
NameTimeMethod
SPID48 (Sum of Pain Intensity Differences Over First 48 Hours of the Multiple-dose Phase)over 48 hours of the multiple-dose phase

Sum of Pain Intensity Differences calculated as the weighted sum of the PI-VAS differences over 48 hours of the multiple-dose phase.

PI-VAS corresponds to the pain intensity measured by a 0-100 visual analogue scale (0=no pain to 100=worst pain imaginable) which was measured every two hours over the first 48 hours of the multiple-dose phase. A higher value in SPID indicates greater pain relief.

The analysis was performed combining all randomization arms including the same active treatment, which resulted in the following 3 analysis groups: DKP/TRAM, DEXKETOPROFEN, and TRAMADOL.

Percentage of Responders According to PI-VAS (Pain Intensity - Visual Analogue Scale)over 48 hours of the multiple-dose phase

Percentage of responders; response defined as achievement a mean pain intensity, PI-VAS \< 40 mm (PI-VAS corresponds to the pain intensity measured by a 0-100 visual analogue scale, 0=no pain to 100=worst pain imaginable),over 48 hours of the multiple-dose phase.

The analysis was performed combining all randomization arms including the same active treatment, which resulted in the following 3 analysis groups: DKP/TRAM, DEXKETOPROFEN, and TRAMADOL.

Percentage of Responders According to 50% Max TOTPAR (Total Pain Relief)over 8 hours after the first dose

Percentage of responders over 8 hours after first dose, according to the 50% maximum total pain relief rule: maximum TOTPAR calculated as the theoretical maximum weighted sum of PAR-VRS (Pain Relief - Verbal Rating Scale: pain relief 0=none, 4=complete) scores.

The analysis was performed combining all randomization arms including placebo into one group, which resulted in the following 4 analysis groups: DKP/TRAM, DEXKETOPROFEN, TRAMADOL, and Placebo.

Trial Locations

Locations (37)

Hospital L'Esperança. Parc de Salut Mar.

🇪🇸

Barcelona, Spain

Warminskie Centrum Ortopedyczne

🇵🇱

Elblag, Poland

University of Debrecen

🇭🇺

Debrecen, Hungary

Fejér Megyei Szent György Kórház

🇭🇺

Székesfehérvár, Hungary

Urazowo - Ortopedycznej Wojewodzkiego Szpitala Specjalistycznego we Wrocławiu

🇵🇱

Wroclaw, Poland

Uzsoki Hospital, Department of Orthopaedics

🇭🇺

Budapest, Hungary

Cherkaska oblasna likarnia

🇺🇦

Cherkasy, Ukraine

PTE KK Trauma Központ-Balesetsebészeti és Kézsebésze

🇭🇺

Pécs, Hungary

Uniwersytecki Szpital Klioniczny w Bialymstoku

🇵🇱

Bialystok, Poland

Wojewodzki Szpital Specjalistyczny

🇵🇱

Lublin, Poland

Specjalistyczny Szpital im. E. Szczeklika

🇵🇱

Tarnow, Poland

Instytut patologii khrebta ta suglobiv im. prof. M.I. Sytenka NAMN Ukraine

🇺🇦

Kharkiv, Ukraine

Clinical Center of Serbia

🇷🇸

Belgrade, Serbia

Kyivska oblasna klinichna likarnia

🇺🇦

Kyiv, Ukraine

Hospital Universitario Puerta del Mar

🇪🇸

Cadiz, Spain

Oblastni nemocnice Kladno

🇨🇿

Kladno, Czech Republic

Liepaja Regional Hospital

🇱🇻

Liepaja, Latvia

Riga's 2nd Hospital

🇱🇻

Riga, Latvia

Hospital of Traumatology and Orthopaedics

🇱🇻

Riga, Latvia

Vidzemes Hospital

🇱🇻

Valmiera, Latvia

Hospital of Lithuanian University of Health Sciences Kaunas

🇱🇹

Kaunas, Lithuania

Respublikine Vilniaus universitetine ligonine

🇱🇹

Vilnius, Lithuania

Clinical Center Kragujevac

🇷🇸

Kragujevac, Serbia

Klinikum Frankfurt Höchst GmbH

🇩🇪

Frankfurt am Main, Germany

MÁV Kórház és Rendelőintézet, Ortopédiai osztály

🇭🇺

Szolnok, Hungary

Fakultni nemocnice Brno

🇨🇿

Brno, Czech Republic

Nemocnice Jihlava, p.o.

🇨🇿

Jihlava, Czech Republic

Klaipedos Universitetine ligonine

🇱🇹

Klaipeda, Lithuania

Clinic for Orthopedic Surgery and Trauma Bul. Dr Zorana Djindjica

🇷🇸

Nis, Serbia

Kuang Tien General Hospital

🇨🇳

Taichung, Taiwan

Urazova nemocnice v Brne

🇨🇿

Brno, Czech Republic

Oblastni nemocnice Mlada Boleslav a.s.

🇨🇿

Mlada Boleslav, Czech Republic

Kaunas Clinical Hospital

🇱🇹

Kaunas, Lithuania

Institute for orthopedic Surgery Banjica [Ortopedic Surgery

🇷🇸

Belgrade, Serbia

China Medical University Hospital [Orthopedic]

🇨🇳

Taichung, Taiwan

Medical University of Lodz

🇵🇱

Lodz, Łódzkie, Poland

Sevastopolska miska likarnia №9

🇺🇦

Sevastopol, Ukraine

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