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

Group	Intervention	Description
Placebo followed by DKP/TRAM	Placebo	Placebo single dose followed by Dexketoprofen/Tramadol-multiple doses
DKP/TRAM followed by DKP/TRAM	Dexketoprofen/Tramadol-single dose	Dexketoprofen/Tramadol-single dose followed by Dexketoprofen/Tramadol-multiple doses
DKP/TRAM followed by DKP/TRAM	Dexketoprofen/Tramadol-multiple doses	Dexketoprofen/Tramadol-single dose followed by Dexketoprofen/Tramadol-multiple doses
DKP followed by DKP	Dexketoprofen-single dose	Dexketoprofen-single dose followed by Dexketoprofen-multiple doses
TRAM followed by TRAM	Tramadol-multiple doses	Tramadol-single dose followed by Tramadol-multiple doses
DKP followed by DKP	Dexketoprofen-multiple doses	Dexketoprofen-single dose followed by Dexketoprofen-multiple doses
TRAM followed by TRAM	Tramadol-single dose	Tramadol-single dose followed by Tramadol-multiple doses
Placebo followed by DKP/TRAM	Dexketoprofen/Tramadol-multiple doses	Placebo single dose followed by Dexketoprofen/Tramadol-multiple doses
Placebo followed by DKP	Placebo	Placebo single dose followed by Dexketoprofen-multiple doses
Placebo followed by DKP	Dexketoprofen-multiple doses	Placebo single dose followed by Dexketoprofen-multiple doses
Placebo followed by TRAM	Placebo	Placebo single dose followed by Tramadol-multiple doses
Placebo followed by TRAM	Tramadol-multiple doses	Placebo single dose followed by Tramadol-multiple doses

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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): Fakultni nemocnice Brno
🇨🇿
Brno, Czech Republic
Urazova nemocnice v Brne
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Brno, Czech Republic
Nemocnice Jihlava, p.o.
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Jihlava, Czech Republic
Oblastni nemocnice Kladno
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Kladno, Czech Republic
Oblastni nemocnice Mlada Boleslav a.s.
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Mlada Boleslav, Czech Republic
Klinikum Frankfurt Höchst GmbH
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Frankfurt am Main, Germany
Uzsoki Hospital, Department of Orthopaedics
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Budapest, Hungary
University of Debrecen
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Debrecen, Hungary
PTE KK Trauma Központ-Balesetsebészeti és Kézsebésze
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Pécs, Hungary
MÁV Kórház és Rendelőintézet, Ortopédiai osztály
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Szolnok, Hungary
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Fakultni nemocnice Brno
🇨🇿Brno, Czech Republic