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Tramadol Hydrochloride and Dexketoprofen Trometamol for the Oral Treatment of Moderate to Severe Acute Pain Following Removal of Impacted Lower Third Molar (DAVID)

Primary Purpose

Acute Pain

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Tramadol Hydrochloride/Dexketoprofen Trometamol
Tramadol Hydrochloride/Paracetamol
Placebo
Sponsored by
Menarini Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Pain focused on measuring Acute pain, Acute moderate to severe pain, Postoperative pain, Dexketoprofen Tramadol, Dexketoprofen trometamol, Tramadol hydrochloride, Multimodal analgesia, Third molar extraction, Fixed drug combination, Paracetamol, Analgesics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female patients aged more than 18 years. Females participating in the study must be either non-childbearing potential or routinely using an effective method of birth control resulting in a low failure rate.
  • Scheduled for outpatient surgical extraction -under local anaesthesia of lower third molar teeth, with at least one partially impacted in the mandible requiring bone manipulation.
  • Pain of at least moderate intensity in the first 4 hours after the end of surgery (NRS score ≥ 4).

Exclusion Criteria:

  • History of allergy or hypersensitivity to the study treatments, RM or to any other NSAIDs, opioids and acetyl salicylic acid.
  • History of peptic ulcer, gastrointestinal disorders by NSAIDs or gastrointestinal bleeding or other active bleedings.
  • History of any illness or condition that, in the opinion of the Investigator might pose a risk to the patient or confound the efficacy and safety results of the study.
  • Patients using and not suitable for withdrawing the prohibited medications specified in the protocol.

Sites / Locations

  • Dr. Tóth Bagi Zoltán Fogászati Rendeloje
  • OralMed Studio Fogászati és Szájsebészeti Kft.
  • Szegedi Tudományegyetem
  • Ospedale Civile San Salvatore di L'Aquila
  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Azienda Ospedaliero-Universitaria Pisana
  • Azienda Ospedaliera Universitaria Integrata
  • Ars-Dent
  • Gabinet Stomatologiczny Andrzej Wojtowicz AW Clinic
  • Charme Clinique Klinika Stomatologii
  • Centro Medico Teknon
  • Hospital Médico Quirúrgico de Conxo
  • Hospital Universitario Virgen del Rocío
  • Universidad de Valencia
  • Birmingham Community Healthcare NHS Foundation Trust
  • University Hospital of Wales
  • University of Manchester
  • University Hospitals of North Midlands NHS Trust

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Tramadol/Dexketoprofen

Tramadol/Paracetamol

Placebo

Arm Description

Tramadol Hydrochloride/Dexketoprofen Trometamol 75mg/25mg film-coated tablet oral single dose; Placebo matching Tramadol Hydrochloride/Paracetamol 75 mg/650mg, as 2 x [37.5mg/325mg] film-coated tablets, oral single dose.

Tramadol Hydrochloride/Paracetamol 75 mg/650 mg, as 2 x [37.5mg/325mg] film-coated tablets, oral single dose; Placebo matching Tramadol Hydrochloride/Dexketoprofen Trometamol 75mg/25mg film-coated tablet oral single dose. .

Placebo matching one film-coated tablet of Tramadol Hydrochloride/Dexketoprofen Trometamol 75mg/25mg oral single dose; Placebo matching two film-coated tablets of Tramadol Hydrochloride/Paracetamol 37.5mg/325mg oral single dose.

Outcomes

Primary Outcome Measures

TOTPAR6 (Total Pain Relief Over 6 Hours Post-dose)
TOTPAR calculated as the weighted sum of the PAR scores, measured according to a 5-point VRS (Verbal Rating Scale) from 0=no relief to 4=complete relief, over 6 hours post-dose (TOTPAR6). The TOTPAR6 ranges from a minimum of 0 to a maximum of 24.

Secondary Outcome Measures

% of Patients Achieving 50% of Max TOTPAR
Percentage of patients who achieved at least 50% of the maximum TOTPAR at 8 hours. In the present trial the achievable TOTPAR over 8 hours ranges between 0 and 32."
% of Patients Achieving at Least 30% of PI (Pain Intensity) Reduction Over 8 Hours Post-dose
Percentage of patients who achieve at least 30% of PI Reduction versus baseline Over 8 Hours Post-dose. Percentage change of PI is calculated using the baseline value minus the PI assessed at 8 hours post-dose divided for the baseline value, then multiplied for 100.
Time to Confirmed FPPAR (First Perceptible Pain Relief)
Time to confirmed FPPAR (time to onset of analgesia) - i.e. time to FPPAR if confirmed by experiencing Meaningful Pain Relief (MPAR) FPPAR and MPAR assessed by using stopwatches: 'first perceptible' PAR (FPPAR), i.e, at the moment they first felt any PAR whatsoever; 'meaningful' PAR (MPAR, ie, when the relief from pain became meaningful to them)
% of Patients Requiring RM (Rescue Medication)
Percentage of patients who required RM within the first over 8 hours post-dose.
PGE (Patient Global Evaluation)
PGE of the study medication (measured according to a five-point VRS from 1 = poor to 5 = excellent) at 8 hours post-dose or whenever the patient uses Rescue Medication (RM).

Full Information

First Posted
May 13, 2016
Last Updated
March 1, 2021
Sponsor
Menarini Group
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1. Study Identification

Unique Protocol Identification Number
NCT02777970
Brief Title
Tramadol Hydrochloride and Dexketoprofen Trometamol for the Oral Treatment of Moderate to Severe Acute Pain Following Removal of Impacted Lower Third Molar
Acronym
DAVID
Official Title
Analgesic Efficacy of Oral Dexketoprofen Trometamol/Tramadol Hydrochloride Versus Tramadol Hydrochloride/Paracetamol: a Randomised, Double-blind, Placebo and Active-controlled, Parallel Group Study in Moderate to Severe Acute Pain After Removal of Impacted Lower Third Molar (Dexketoprofen Analgesic eVolution wIth tramaDol- DAVID Study)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
April 2016 (Actual)
Primary Completion Date
February 14, 2017 (Actual)
Study Completion Date
February 14, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Menarini Group

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The study is aimed to evaluate the analgesic efficacy of TRAM.HCl/DKP.TRIS 75mg/25mg oral fixed drug combination in comparison with TRAM.HCl /paracetamol 75mg/650mg in the treatment of moderate to severe acute pain.
Detailed Description
The present phase IV study is a randomised, double-blind, placebo and active-controlled, parallel group study in moderate to severe acute pain after removal of impacted lower third molar. In this single-dose clinical trial patients are randomized to the following 3 treatment arms in a 2:2:1 ratio: TRAM.HCL/DKP.TRIS Paracetamol/TRAM.HCL Placebo.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Pain
Keywords
Acute pain, Acute moderate to severe pain, Postoperative pain, Dexketoprofen Tramadol, Dexketoprofen trometamol, Tramadol hydrochloride, Multimodal analgesia, Third molar extraction, Fixed drug combination, Paracetamol, Analgesics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
654 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tramadol/Dexketoprofen
Arm Type
Experimental
Arm Description
Tramadol Hydrochloride/Dexketoprofen Trometamol 75mg/25mg film-coated tablet oral single dose; Placebo matching Tramadol Hydrochloride/Paracetamol 75 mg/650mg, as 2 x [37.5mg/325mg] film-coated tablets, oral single dose.
Arm Title
Tramadol/Paracetamol
Arm Type
Active Comparator
Arm Description
Tramadol Hydrochloride/Paracetamol 75 mg/650 mg, as 2 x [37.5mg/325mg] film-coated tablets, oral single dose; Placebo matching Tramadol Hydrochloride/Dexketoprofen Trometamol 75mg/25mg film-coated tablet oral single dose. .
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo matching one film-coated tablet of Tramadol Hydrochloride/Dexketoprofen Trometamol 75mg/25mg oral single dose; Placebo matching two film-coated tablets of Tramadol Hydrochloride/Paracetamol 37.5mg/325mg oral single dose.
Intervention Type
Drug
Intervention Name(s)
Tramadol Hydrochloride/Dexketoprofen Trometamol
Intervention Type
Drug
Intervention Name(s)
Tramadol Hydrochloride/Paracetamol
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
TOTPAR6 (Total Pain Relief Over 6 Hours Post-dose)
Description
TOTPAR calculated as the weighted sum of the PAR scores, measured according to a 5-point VRS (Verbal Rating Scale) from 0=no relief to 4=complete relief, over 6 hours post-dose (TOTPAR6). The TOTPAR6 ranges from a minimum of 0 to a maximum of 24.
Time Frame
6 hours post-dose
Secondary Outcome Measure Information:
Title
% of Patients Achieving 50% of Max TOTPAR
Description
Percentage of patients who achieved at least 50% of the maximum TOTPAR at 8 hours. In the present trial the achievable TOTPAR over 8 hours ranges between 0 and 32."
Time Frame
8 hours post-dose
Title
% of Patients Achieving at Least 30% of PI (Pain Intensity) Reduction Over 8 Hours Post-dose
Description
Percentage of patients who achieve at least 30% of PI Reduction versus baseline Over 8 Hours Post-dose. Percentage change of PI is calculated using the baseline value minus the PI assessed at 8 hours post-dose divided for the baseline value, then multiplied for 100.
Time Frame
8 hours post-dose
Title
Time to Confirmed FPPAR (First Perceptible Pain Relief)
Description
Time to confirmed FPPAR (time to onset of analgesia) - i.e. time to FPPAR if confirmed by experiencing Meaningful Pain Relief (MPAR) FPPAR and MPAR assessed by using stopwatches: 'first perceptible' PAR (FPPAR), i.e, at the moment they first felt any PAR whatsoever; 'meaningful' PAR (MPAR, ie, when the relief from pain became meaningful to them)
Time Frame
2 hours post-dose
Title
% of Patients Requiring RM (Rescue Medication)
Description
Percentage of patients who required RM within the first over 8 hours post-dose.
Time Frame
8 hours post-dose
Title
PGE (Patient Global Evaluation)
Description
PGE of the study medication (measured according to a five-point VRS from 1 = poor to 5 = excellent) at 8 hours post-dose or whenever the patient uses Rescue Medication (RM).
Time Frame
8 hours postdose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female patients aged more than 18 years. Females participating in the study must be either non-childbearing potential or routinely using an effective method of birth control resulting in a low failure rate. Scheduled for outpatient surgical extraction -under local anaesthesia of lower third molar teeth, with at least one partially impacted in the mandible requiring bone manipulation. Pain of at least moderate intensity in the first 4 hours after the end of surgery (NRS score ≥ 4). Exclusion Criteria: History of allergy or hypersensitivity to the study treatments, RM or to any other NSAIDs, opioids and acetyl salicylic acid. History of peptic ulcer, gastrointestinal disorders by NSAIDs or gastrointestinal bleeding or other active bleedings. History of any illness or condition that, in the opinion of the Investigator might pose a risk to the patient or confound the efficacy and safety results of the study. Patients using and not suitable for withdrawing the prohibited medications specified in the protocol.
Facility Information:
Facility Name
Dr. Tóth Bagi Zoltán Fogászati Rendeloje
City
Budapest
ZIP/Postal Code
1052
Country
Hungary
Facility Name
OralMed Studio Fogászati és Szájsebészeti Kft.
City
Budapest
ZIP/Postal Code
1126
Country
Hungary
Facility Name
Szegedi Tudományegyetem
City
Szeged
ZIP/Postal Code
6725
Country
Hungary
Facility Name
Ospedale Civile San Salvatore di L'Aquila
City
L'Aquila
ZIP/Postal Code
67100
Country
Italy
Facility Name
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
City
Milan
ZIP/Postal Code
20122
Country
Italy
Facility Name
Azienda Ospedaliero-Universitaria Pisana
City
Pisa
ZIP/Postal Code
56126
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Integrata
City
Verona
ZIP/Postal Code
37134
Country
Italy
Facility Name
Ars-Dent
City
Bialystok
ZIP/Postal Code
15-078
Country
Poland
Facility Name
Gabinet Stomatologiczny Andrzej Wojtowicz AW Clinic
City
Warszawa
ZIP/Postal Code
00-852
Country
Poland
Facility Name
Charme Clinique Klinika Stomatologii
City
Warszawa
ZIP/Postal Code
02-670
Country
Poland
Facility Name
Centro Medico Teknon
City
Barcelona
ZIP/Postal Code
08022
Country
Spain
Facility Name
Hospital Médico Quirúrgico de Conxo
City
La Coruna
ZIP/Postal Code
15702
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocío
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Facility Name
Universidad de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Birmingham Community Healthcare NHS Foundation Trust
City
Birmingham
ZIP/Postal Code
B4 6NN
Country
United Kingdom
Facility Name
University Hospital of Wales
City
Cardiff
ZIP/Postal Code
CF14 4XT
Country
United Kingdom
Facility Name
University of Manchester
City
Manchester
ZIP/Postal Code
M15 6FH
Country
United Kingdom
Facility Name
University Hospitals of North Midlands NHS Trust
City
Stoke on Trent
ZIP/Postal Code
ST4 6QG
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30782886
Citation
Gay-Escoda C, Hanna M, Montero A, Dietrich T, Milleri S, Giergiel E, Zoltan TB, Varrassi G. Tramadol/dexketoprofen (TRAM/DKP) compared with tramadol/paracetamol in moderate to severe acute pain: results of a randomised, double-blind, placebo and active-controlled, parallel group trial in the impacted third molar extraction pain model (DAVID study). BMJ Open. 2019 Feb 19;9(2):e023715. doi: 10.1136/bmjopen-2018-023715. Erratum In: BMJ Open. 2019 Jun 14;9(6):e023715corr1.
Results Reference
derived

Learn more about this trial

Tramadol Hydrochloride and Dexketoprofen Trometamol for the Oral Treatment of Moderate to Severe Acute Pain Following Removal of Impacted Lower Third Molar

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