Clinical trial NCT01307020: Analgesic Effect of Different Combinations of Dexketoprofen Trometamol With Tramadol Hydrochloride in a Model of Moderate to Severe Pain
Official title: Double-blind, Randomised, Placebo and Active Controlled, Parallel Group Study to Evaluate the Analgesic Effect of a Single Oral Administration of Four Different Combination Doses of DKP.TRIS With TRAM.HCL in Comparison With the Single Agents, on Moderate to Severe Pain Following Impacted Third Mandibular Molar Tooth Extraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pain
Keywords: Moderate to severe pain
Postoperative pain
Analgesics
Dexketoprofen
Tramadol
Lead sponsor: Menarini Group
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
First posted: 2011-03-02
Enrollment: 745
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Patients Achieving at Least 50 % of the Theoretical Maximum Total Pain Relief Score at 6 Hours Post-dosing.
timeFrame: 6 hours
Secondary outcomes:
measure: Percentage of Patients Achieving at Least 50 % of the Theoretical Maximum Total Pain Relief Score at 4, 8 and 12 Hours Post-dosing.
timeFrame: 4, 8 and 12 hours
measure: Percentage of Patients Using Rescue Medication at 6 Hours
timeFrame: Baseline to 6 hours
Other outcomes:
Locations:
city: Greifswald
country: Germany
facility: Klinik und Polickinik für Mund-Kiefer-Gesichtschirurgie/Plastische Operationen Greifswald
state: Mecklenburg-Vorpommern
city: Kiel
country: Germany
facility: Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitätsklinikum Schleswig Holstein, Campus Kiel
state: Schleswig-Holstein
city: Budapest
country: Hungary
facility: Dr Tóth Bagi Zoltán Fogászati Rendeloje
city: Pisa
country: Italy
facility: Centro di Farmacologia Clinica per la Sperimentazione dei Farmaci
city: Verona
country: Italy
facility: Centro di Ricerche Cliniche di Verona Srl. Policlinico G.B.Rossi
city: Warsaw
country: Poland
facility: Gabinet Stomatologiczny Andrzej Wojtowicz AW Clinic
state: Mazowieckie
city: Warszawa
country: Poland
facility: Dental Service spólka jawna
state: Mazowieckie
city: Santiago de Compostela
country: Spain
facility: Hospital Médico Quirúrgico de Conxo
state: A Coruña
city: L'Hospitalet de Llobregat
country: Spain
facility: Facultad de Odontología. Departamento de Cirugía Bucal y Maxilofacial, University of Barcelona - Bellvitge Institute for Biomedical Research (IDIBELL)
state: Barcelona
city: Madrid
country: Spain
facility: Universidad Complutense de Madrid
city: Sevilla
country: Spain
facility: Departamento de Estomatología, Facultad de Odontología. Universidad de Sevilla
city: Valencia
country: Spain
facility: Departament d'Estomatologia, Clínica Odontològica, Universidad de Valencia - Fundació Lluís Alcanyís
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Birmingham
country: United Kingdom
facility: The School of Dentistry, College of Medical and Dental Sciences, University of Birmingham
state: England
city: Manchester
country: United Kingdom
facility: University Dental School Manchester
state: England
city: Cardiff
country: United Kingdom
facility: University Dental Hospital
state: Wales
Study officials:
affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Barcelona - Bellvitge Institute for Biomedical Research (IDIBELL) 08907 Hospitalet de Llobregat, Barcelona (Spain)
name: Cosme Gay-Escoda, Professor
role: STUDY_CHAIR
affiliation: Pain Research & Nuffield Division of Anaesthesics, Department of Clinical Neurosciences, University of Oxford. The Churchill, Oxford OX3 7LJ (United Kingdom)
name: R Andrew Moore, Professor
role: STUDY_CHAIR
References:
citation: Moore RA, Gay-Escoda C, Figueiredo R, Toth-Bagi Z, Dietrich T, Milleri S, Torres-Lagares D, Hill CM, Garcia-Garcia A, Coulthard P, Wojtowicz A, Matenko D, Penarrocha-Diago M, Cuadripani S, Piza-Vallespir B, Guerrero-Bayon C, Bertolotti M, Contini MP, Scartoni S, Nizzardo A, Capriati A, Maggi CA. Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain. J Headache Pain. 2015;16:541. doi: 10.1186/s10194-015-0541-5. Epub 2015 Jun 27.