Acute PainPhase 4DAVIDNCT02777970
Tramadol Hydrochloride and Dexketoprofen Trometamol for the Oral Treatment of Moderate to Severe Acute Pain Following Removal of Impacted Lower Third Molar
A Phase 4 study testing Tramadol Hydrochloride/Dexketoprofen Trometamol and Tramadol Hydrochloride/Paracetamol in people with Acute Pain, run by Menarini Group at 18 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Pain
- What is being tested?
- Tramadol Hydrochloride/Dexketoprofen Trometamol and Tramadol Hydrochloride/Paracetamol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 654 participants
- Where
- 18 sitesin 5 countries
- Study dates
- Apr 2016to 14 Feb 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
18 sites in 5 countries.
18 sites in 5 countries
Italy4 sites
Ospedale Civile San Salvatore di L'Aquila
L’Aquila, 67100
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, 20122
Azienda Ospedaliero-Universitaria Pisana
Pisa, 56126
Azienda Ospedaliera Universitaria Integrata
Verona, 37134
Spain4 sites
Hospital Médico Quirúrgico de Conxo
A Coruña, 15702
Centro Medico Teknon
Barcelona, 08022
Hospital Universitario Virgen del Rocío
Seville, 41009
Universidad de Valencia
Valencia, 46010
United Kingdom4 sites
Birmingham Community Healthcare NHS Foundation Trust
Birmingham, B4 6NN
University Hospital of Wales
Cardiff, CF14 4XT
University of Manchester
Manchester, M15 6FH
University Hospitals of North Midlands NHS Trust
Stoke-on-Trent, ST4 6QG
Hungary3 sites
Dr. Tóth Bagi Zoltán Fogászati Rendeloje
Budapest, 1052
OralMed Studio Fogászati és Szájsebészeti Kft.
Budapest, 1126
Szegedi Tudományegyetem
Szeged, 6725
Poland3 sites
Ars-Dent
Bialystok, 15-078
Gabinet Stomatologiczny Andrzej Wojtowicz AW Clinic
Warsaw, 00-852
Charme Clinique Klinika Stomatologii
Warsaw, 02-670
About this study
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)
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.
Read the 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.
- Conditions
- Acute Pain
- Being tested
- Tramadol Hydrochloride/Dexketoprofen Trometamol, Tramadol Hydrochloride/Paracetamol, Placebo
- 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
- Medical subject headings
- Acute Pain, Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tramadol Hydrochloride/Dexketoprofen TrometamolDrug
Tramadol Hydrochloride/ParacetamolDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Tramadol/Dexketoprofen | Experimental | 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. Receives: Drug: Tramadol Hydrochloride/Dexketoprofen Trometamol; Drug: Placebo |
| Tramadol/Paracetamol | Active comparator | 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.
. Receives: Drug: Tramadol Hydrochloride/Paracetamol; Drug: Placebo |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 hours post-dose
Secondary outcomes (5)
% 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."
Measured: 8 hours post-dose
% 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.
Measured: 8 hours post-dose
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)
Measured: 2 hours post-dose
% of Patients Requiring RM (Rescue Medication)
Percentage of patients who required RM within the first over 8 hours post-dose.
Measured: 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).
Measured: 8 hours postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2016 (estimated)
- Study startApr 2016
- Primary completion14 Feb 2017
- Study completion14 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 654 participants (actual)
Sponsor and investigators
- Lead sponsor
- Menarini Group
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02777970
- Sponsor's protocol ID
- DEX-TRA-06
- Acronym
- DAVID
- Status last verified
- Mar 2021
- First submitted
- 13 May 2016
- Last updated
- 24 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 30782886
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02777970
- Acronym / sponsor ID
- DAVID / DEX-TRA-06
- Conditions
- Acute Pain
- Keywords
- Acute pain, Acute moderate to severe pain, Postoperative pain, Dexketoprofen Tramadol, Dexketoprofen trometamol, Tramadol hydrochloride, Multimodal analgesia, Third molar extraction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 654 participants (actual)
- Lead sponsor
- Menarini GroupIndustry (pharma, biotech, devices)
- Study start
- Apr 2016 (actual)
- Primary completion
- 14 Feb 2017 (actual)
- Study completion
- 14 Feb 2017 (actual)
- First posted
- 19 May 2016 (estimated)
- Results
- Posted 24 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tramadol/Dexketoprofen | Experimental | Drug: Tramadol Hydrochloride/Dexketoprofen Trometamol, Drug: PlaceboTramadol 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/Paracetamol | Active comparator | Drug: Tramadol Hydrochloride/Paracetamol, Drug: PlaceboTramadol 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 | Placebo comparator | Drug: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tramadol Hydrochloride/Dexketoprofen Trometamol | Drug | Tramadol/Dexketoprofen |
| Tramadol Hydrochloride/Paracetamol | Drug | Tramadol/Paracetamol |
| Placebo | Drug | Placebo, Tramadol/Dexketoprofen, Tramadol/Paracetamol |
Primary outcome
TOTPAR6 (Total Pain Relief Over 6 Hours Post-dose)
Time frame: 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.
5 secondary outcomes
% of Patients Achieving 50% of Max TOTPAR
Time frame: 8 hours post-dose
% of Patients Achieving at Least 30% of PI (Pain Intensity) Reduction Over 8 Hours Post-dose
Time frame: 8 hours post-dose
Time to Confirmed FPPAR (First Perceptible Pain Relief)
Time frame: 2 hours post-dose
% of Patients Requiring RM (Rescue Medication)
Time frame: 8 hours post-dose
PGE (Patient Global Evaluation)
Time frame: 8 hours postdose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30782886Gay-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.
- Individual participant dataSharing planned: No
Related trials for Acute Pain
Not yet recruiting
Human Experimental Models of Pain (HEMP)
Acute Pain
RecruitingPhase 2
REctus Sheath Trial
Acute Pain, Postoperative Pain, Acute
Not yet recruitingPhase 2
A Clinical Trial of MK-6916 in Participants With Pain After Bunion Removal Surgery (MK-6916-007)
Pain Management
Not yet recruitingPhase 2
Investigating the Analgesic Potential of (2R,6R)-HNK in Acute Pain in Healthy Volunteers
Healthy Volunteers
Not yet recruiting
Post-operative Pain and Clinical Outcome After Single-cone Obturation With a Calcium Silicate-based Versus Epoxy Resin Sealer
Post Operative Pain, Acute, Irreversible Pulpitis (Toothache)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
18 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tramadol Hydrochloride/Dexketoprofen Trometamol and Tramadol Hydrochloride/Paracetamol in people with Acute Pain, run by Menarini Group at 18 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in Italy, Spain, United Kingdom, Hungary, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TOTPAR6 (Total Pain Relief Over 6 Hours Post-dose) (time frame: 6 hours post-dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02777970, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2021.