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

Acute Pain Clinical Trial

— DAVID-art  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01902134
• Other study ID #: DEX-TRA-05
• Secondary ID: 2012-004548-31
• Status: Completed
• Phase: Phase 3
• First received: July 15, 2013
• Last updated: February 4, 2016
• Start date: April 2013
• Est. completion date: February 2014

Study information

• Verified date: February 2016
• Source: Menarini Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Czech Republic: State Institute for Drug ControlGermany: Federal Institute for Drugs and Medical DevicesHungary: Research Ethics Medical CommitteeLatvia: State Agency of MedicinesLithuania: State Medicine Control Agency - Ministry of HealthPoland: Ministry of HealthSerbia: Medicines and Medical Devices AgencySpain: Ministry of HealthTaiwan : Food and Drug AdministrationUkraine: State Pharmacological Center - Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 641
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Pain

Intervention

Drug:
• Placebo
Placebo single oral dose (first 8 hours)
• Tramadol-single dose
Tramadol single oral dose (first 8 hours)
• Dexketoprofen-single dose
Dexketoprofen single oral dose (first 8 hours)
• Dexketoprofen/Tramadol-single dose
Dexketoprofen/Tramadol oral single dose (first 8 hours)
• Tramadol-multiple doses
Tramadol multiple oral doses t.i.d. for 5 days (total 12 doses)
• Dexketoprofen-multiple doses
Dexketoprofen multiple oral doses t.i.d. for 5 days (total 12 doses)
• Dexketoprofen/Tramadol-multiple doses
Dexketoprofen/Tramadol multiple oral doses t.i.d. for 5 days (total 12 doses)

Locations

Country	Name	City	State
Czech Republic	Fakultni nemocnice Brno	Brno
Czech Republic	Urazova nemocnice v Brne	Brno
Czech Republic	Nemocnice Jihlava, p.o.	Jihlava
Czech Republic	Oblastni nemocnice Kladno	Kladno
Czech Republic	Oblastni nemocnice Mlada Boleslav a.s.	Mlada Boleslav
Germany	Klinikum Frankfurt Höchst GmbH	Frankfurt am Main
Hungary	Uzsoki Hospital, Department of Orthopaedics	Budapest
Hungary	University of Debrecen	Debrecen
Hungary	PTE KK Trauma Központ-Balesetsebészeti és Kézsebésze	Pécs
Hungary	Fejér Megyei Szent György Kórház	Székesfehérvár
Hungary	MÁV Kórház és Rendelointézet, Ortopédiai osztály	Szolnok
Latvia	Liepaja Regional Hospital	Liepaja
Latvia	Hospital of Traumatology and Orthopaedics	Riga
Latvia	Riga's 2nd Hospital	Riga
Latvia	Vidzemes Hospital	Valmiera
Lithuania	Hospital of Lithuanian University of Health Sciences Kaunas	Kaunas
Lithuania	Kaunas Clinical Hospital	Kaunas
Lithuania	Klaipedos Universitetine ligonine	Klaipeda
Lithuania	Respublikine Vilniaus universitetine ligonine	Vilnius
Poland	Uniwersytecki Szpital Klioniczny w Bialymstoku	Bialystok
Poland	Warminskie Centrum Ortopedyczne	Elblag
Poland	Medical University of Lodz	Lodz	Lódzkie
Poland	Wojewodzki Szpital Specjalistyczny	Lublin
Poland	Specjalistyczny Szpital im. E. Szczeklika	Tarnow
Poland	Urazowo - Ortopedycznej Wojewodzkiego Szpitala Specjalistycznego we Wroclawiu	Wroclaw
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Institute for orthopedic Surgery Banjica [Ortopedic Surgery	Belgrade
Serbia	Clinical Center Kragujevac	Kragujevac
Serbia	Clinic for Orthopedic Surgery and Trauma Bul. Dr Zorana Djindjica	Nis
Spain	Hospital L'Esperança. Parc de Salut Mar.	Barcelona
Spain	Hospital Universitario Puerta del Mar	Cadiz
Taiwan	China Medical University Hospital [Orthopedic]	Taichung
Taiwan	Kuang Tien General Hospital	Taichung
Ukraine	Cherkaska oblasna likarnia	Cherkasy
Ukraine	Instytut patologii khrebta ta suglobiv im. prof. M.I. Sytenka NAMN Ukraine	Kharkiv
Ukraine	Kyivska oblasna klinichna likarnia	Kyiv
Ukraine	Sevastopolska miska likarnia ?9	Sevastopol

Sponsors (1)

Lead Sponsor	Collaborator
Menarini Group

Countries where clinical trial is conducted

Czech Republic,  Germany,  Hungary,  Latvia,  Lithuania,  Poland,  Serbia,  Spain,  Taiwan,  Ukraine, 

References & Publications (1)

McQuay HJ, Moore RA, Berta A, Gainutdinovs O, Fülesdi B, Porvaneckas N, Petronis S, Mitkovic M, Bucsi L, Samson L, Zegunis V, Ankin ML, Bertolotti M, Pizà-Vallespir B, Cuadripani S, Contini MP, Nizzardo A. Randomized clinical trial of dexketoprofen/tramad — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SPID8 (Sum of Pain Intensity Differences Over 8 Hours)	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.	over 8 hours after the first dose	No
Secondary	SPID48 (Sum of Pain Intensity Differences Over First 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.	over 48 hours of the multiple-dose phase	No
Secondary	Percentage of Responders According to PI-VAS (Pain Intensity - Visual Analogue Scale)	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.	over 48 hours of the multiple-dose phase	No
Secondary	Percentage of Responders According to 50% Max TOTPAR (Total Pain Relief)	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.	over 8 hours after the first dose	No

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