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Analgesic Effect of Different Combinations of Dexketoprofen Trometamol With Tramadol Hydrochloride in a Model of Moderate to Severe Pain

Registration Number
NCT01307020
Lead Sponsor
Menarini Group
Brief Summary

The purpose of this study is to evaluate the analgesic efficacy of Dexketoprofen Trometamol and Tramadol Hydrochloride given in combinations and the analgesic efficacy of each single component in comparison to placebo on moderate to severe pain following impacted third mandibular molar tooth extraction. Ibuprofen will be used as an active control to validate the pain model.

Detailed Description

The aim of this study is to develop a combination of Dexketoprofen Trometamol (DKP.TRIS) and Tramadol Hydrochloride (TRAM.HCl) for the treatment of acute moderate to severe pain, based on the rationale that more than one drug is necessary in most patients suffering of acute and chronic pain, particularly of moderate to severe intensity.

DKP.TRIS and TRAM.HCl have different mechanisms of action, therefore their combination is expect to result in an additive or synergistic analgesia, thus allowing a decrease in the required doses of the individual agents, and consequently a reduced risk of adverse events In this study, patients who present moderate to severe pain after impacted third mandibular molar tooth extraction will be randomised to a total of 10 treatment arms including 4 combinations of DKP.TRIS + TRAM.HCl, the four corresponding single treatments, placebo and ibuprofen. Treatment administration will be followed by a 24-hour pain and analgesic effect assessment.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
745
Inclusion Criteria

Patients meeting ALL the following criteria will be eligible for entry into the study:

  • Male or female patients aged 18 to 70 years old. Females participating in the study must be either: of non-childbearing potential, or willing to use a highly effective contraceptive method.
  • Scheduled for outpatient surgical extraction -under local anaesthesia- of third mandibular molar teeth, with at least one of which is fully or partially impacted in the mandible requiring bone manipulation.
  • Normal physical examination or without clinically relevant abnormalities.

At randomisation (after surgery):

No intake of analgesics (including prescription and over the counter drugs) within 24h prior to the surgery.

  • No complication during the surgery, duration of surgery < 1 hour and not requiring re-anaesthesia.
  • Patients experiencing pain of moderate or higher intensity in the first four hours after the end of surgery.
Exclusion Criteria
  • History of allergy or hypersensitivity to NSAIDs, opioids or acetyl salicylic acid.
  • History of asthma, bronchospasm, acute rhinitis, nasal polyps, urticaria or angioneurotic oedema.
  • History of peptic ulcer, gastrointestinal disorders by NSAIDs, gastrointestinal bleeding or other active bleedings.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DKP-TRIS low doseDexketoprofen Trometamol-
DKP-TRIS high dose - TRAM.HCl low doseDexketoprofen Trometamol + Tramadol Hydrochloride-
DKP-TRIS high dose - TRAM.HCl high doseDexketoprofen Trometamol + Tramadol Hydrochloride-
PlaceboPlacebo-
IbuprofenIbuprofen-
TRAM.HCl high doseTramadol Hydrochloride-
DKP-TRIS high doseDexketoprofen Trometamol-
DKP-TRIS low dose - TRAM.HCl low doseDexketoprofen Trometamol + Tramadol Hydrochloride-
DKP-TRIS low dose - TRAM.HCl high doseDexketoprofen Trometamol + Tramadol Hydrochloride-
TRAM.HCl low doseTramadol Hydrochloride-
Primary Outcome Measures
NameTimeMethod
Percentage of Patients Achieving at Least 50 % of the Theoretical Maximum Total Pain Relief Score at 6 Hours Post-dosing.6 hours

Pain relief is measured by a verbal rating scale (ranging from 0=none to 4=complete). Theoretical maximum TOTPAR at 6 hours is calculated by summing up the maximum score of analgesia which the patient can attribute at defined time points along 6 hour (maxTOTPAR6h= 24). Unit of measure is %

Secondary Outcome Measures
NameTimeMethod
Percentage of Patients Achieving at Least 50 % of the Theoretical Maximum Total Pain Relief Score at 4, 8 and 12 Hours Post-dosing.4, 8 and 12 hours

Pain relief is measured by a verbal rating scale (ranging from 0=none to 4=complete). Theoretical maximum TOTPAR at 6 hours is calculated by summing up the maximum score of analgesia which the patient can attribute at defined time points along 4, 8 and 12 hours(maxTOTPAR4h= 16, maxTOTPAR8h= 32 and maxTOTPAR12h= 48, respectively) Unit of measure is %

Percentage of Patients Using Rescue Medication at 6 HoursBaseline to 6 hours

Percentage of patients using rescue medication at 6 hours post-dosing.

Trial Locations

Locations (16)

Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitätsklinikum Schleswig Holstein, Campus Kiel

🇩🇪

Kiel, Schleswig-Holstein, Germany

Centro di Ricerche Cliniche di Verona Srl. Policlinico G.B.Rossi

🇮🇹

Verona, Italy

University Dental School Manchester

🇬🇧

Manchester, England, United Kingdom

Centro di Farmacologia Clinica per la Sperimentazione dei Farmaci

🇮🇹

Pisa, Italy

Hospital Médico Quirúrgico de Conxo

🇪🇸

Santiago de Compostela, A Coruña, Spain

Universidad Complutense de Madrid

🇪🇸

Madrid, Spain

Departamento de Estomatología, Facultad de Odontología. Universidad de Sevilla

🇪🇸

Sevilla, Spain

Departament d'Estomatologia, Clínica Odontològica, Universidad de Valencia - Fundació Lluís Alcanyís

🇪🇸

Valencia, Spain

University Dental Hospital

🇬🇧

Cardiff, Wales, United Kingdom

Hospital General Universitario de Valencia

🇪🇸

Valencia, Spain

The School of Dentistry, College of Medical and Dental Sciences, University of Birmingham

🇬🇧

Birmingham, England, United Kingdom

Facultad de Odontología. Departamento de Cirugía Bucal y Maxilofacial, University of Barcelona - Bellvitge Institute for Biomedical Research (IDIBELL)

🇪🇸

L'Hospitalet de Llobregat, Barcelona, Spain

Gabinet Stomatologiczny Andrzej Wojtowicz AW Clinic

🇵🇱

Warsaw, Mazowieckie, Poland

Dental Service spólka jawna

🇵🇱

Warszawa, Mazowieckie, Poland

Klinik und Polickinik für Mund-Kiefer-Gesichtschirurgie/Plastische Operationen Greifswald

🇩🇪

Greifswald, Mecklenburg-Vorpommern, Germany

Dr Tóth Bagi Zoltán Fogászati Rendeloje

🇭🇺

Budapest, Hungary

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