Post-surgical PainPhase 4Tradol-PriMENCT05657704
Utility of CYP2D6 Genotyping to Improve the Efficacy and Safety of Tramadol
A Phase 4 study testing The patients in experimental group will be genotyped before surgery and treatment will be prescribed according to the CYP2D6 phenotype in people with Post-surgical Pain and Pain, Acute, run by Fundación de Investigación Biomédica - Hospital Universitario de La Princesa at 8 sites in Spain.
Trial summary
Randomized clinical trial to evaluate the utility of CYP2D6 genotyping to improve the efficacy and safety of tramadol in the treatment of acute postoperative pain. Phase IV and low-intervention trial To evaluate if the implementation of pharmacogenetics in clinical practice can help to improve the treatment of acute… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Post-surgical Pain, Pain, Acute, Postoperative Pain
- What is being tested?
- The patients in experimental group will be genotyped before surgery and treatment will be prescribed according to the CYP2D6 phenotype
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 8 sitesSpain
- Study dates
- 5 Oct 2022to 31 Aug 2026
- Phase
- Phase 4
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men or women over 18 years of age.
- Patients scheduled for outpatient surgical extraction, under local anesthesia, of at least two impacted third molars, at least one of which will require bone removal.
- Patients who agree to participate in the study and give written consent.
Who cannot join
- Patients under treatment with other drugs that can inhibit CYP2D6, or are contraindicated in combination with tramadol or dexketoprofen.
- Patients on treatment with bisphosphonates.
- Patients who are receiving analgesic treatment before the operation, 24 hours prior to the operation. This criterion will be evaluated at the intervention visit.
- Patients suffering from other uncontrolled diseases.
- Pregnant or breastfeeding women.
- Patients with contraindications for treatment with tramadol or dexketoprofen.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Spain8 sites
Hospital Universitario San Juan de Alicante
Alicante, 03550
Hospital General Universitario de Burgos y Clínica Colina
Burgos, 09006
Fundación para la Investigación Biomédica Hospital La Princesa
Madrid, 28006
Hospital Univesitario Ramón y Cajal
Madrid, 28034
Hospital Universitario Clínico San Carlos
Madrid, 28040
Hostpital Universitario Fundación Jiménez Díaz
Madrid, 28040
Hospital Universitaro La Paz
Madrid, 28046
Hospital Universitario Puerta de Hierro
Majadahonda, Madrid, 28220
About this study
Official title: Randomized Clinical Trial to Evaluate the Utility of CYP2D6 Genotyping to Improve the Efficacy and Safety of Tramadol in the Treatment of Acute Postoperative Pain.
Randomized clinical trial to evaluate the utility of CYP2D6 genotyping to improve the efficacy and safety of tramadol in the treatment of acute postoperative pain.
Phase IV and low-intervention trial To evaluate if the implementation of pharmacogenetics in clinical practice can help to improve the treatment of acute pain, increasing efficacy and reducing adverse reactions.
The main evaluation variable: This is a simple study, which does not differ from standard clinical practice and therefore we do not expect early ending of the study.
Read the detailed description
Randomized clinical trial to evaluate the utility of CYP2D6 genotyping to improve the efficacy and safety of tramadol in the treatment of acute postoperative pain.
Phase IV and low-intervention trial The main objective is evaluate if the implementation of pharmacogenetics in clinical practice can help to improve the treatment of acute pain, increasing efficacy and reducing adverse reactions. Secondary objectives: 1. To evaluate whether treatment adjusted according to CYP2D6 phenotype can reduce adverse reactions to tramadol in acute postoperative pain. 2. To compare the efficacy and safety of dexketoprofen and tramadol in the treatment of acute postoperative pain. 3. To investigate the influence on analgesic response and the incidence of adverse reactions of polymorphisms of other genes involved in the pharmacokinetics and mechanism of action of dexketoprofen and tramadol, such as: CYP2C9, CYP2C8, CYP2C19, CYP3A4, CYP3A5, CYP2B6, CYP2E1, COMT, ABCB1, SLC22A1, OPRM1 and PTGS2. 4. To evaluate the relationship of tramadol, M1 and dexketoprofen plasma concentrations with response to treatment and the occurrence of adverse reactions.
Inclusion criteria: 1. Men or women over 18 years of age. 2. Patients scheduled for outpatient surgical extraction, under local anesthesia, of at least two impacted third molars, at least one of which will require bone removal. 3. Patients who agree to participate in the study and give written consent.
Exclusion criteria: 1. Patients under treatment with other drugs that can inhibit CYP2D6, or are contraindicated in combination with tramadol or dexketoprofen. 2. Patients on treatment with bisphosphonates. 3. Patients who are receiving analgesic treatment before the operation, 24 hours prior to the operation. This criterion will be evaluated at the intervention visit. 4. Patients suffering from other uncontrolled diseases. 5. Pregnant or breastfeeding women. 6. Patients with contraindications for treatment with tramadol or dexketoprofen.
- Conditions
- Post-surgical Pain, Pain, Acute, Postoperative Pain
- Being tested
- The patients in experimental group will be genotyped before surgery and treatment will be prescribed according to the CYP2D6 phenotype
- Keywords
- Pharmacogenetics, Therapeutic techniques in treatment of acute postoperative pain
- Medical subject headings
- Pain, Postoperative, Acute Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
The patients in experimental group will be genotyped before surgery and treatment will be prescribed according to the CYP2D6 phenotypeDrug
Also called Tramadol 100 mg, Tramadol 50 mg, Dexketoprofen 25 mg
Treatment will be prescribed according to the CYP2D6 phenotype. Normal Metabolizers (NM): Tramadol 100 mg every 8 hour; Ultrarapid Metabolizers (UM): Tramadol 50 mg every 8 hours Intermediate and poor metabolizers (IM/PM): dexketoprofen 25 mg every 8 hours
| Study group | Role | What they receive |
|---|---|---|
| Tramadol | No intervention | Patients treated with Tramadol, 100 mg every 8 hours according to clinical practice for the treatment of postoperative pain. |
| Dexketoprofen | No intervention | Patients treated with Dexketoprofen 25 mg every 8 hours according to clinical practice for the treatment of postoperative pain. |
| Experimental Group | Experimental | The patients in this group will be genotyped before surgery and treatment will be prescribed according to the CYP2D6 phenotype.
Normal Metabolizers (NM): Tramadol 100 mg every 8 hour; Ultrarapid Metabolizers (UM): Tramadol 50 mg every 8 hours Intermediate and poor metabolizers (IM/PM): dexketoprofen 25 mg every 8 hours Receives: Drug: The patients in experimental group will be genotyped before surgery and treatment will be prescribed according to the CYP2D6 phenotype |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy: analgesic effect (Pain assessment) 4 hours after treatment
To evaluate the analgesic effect (pain assessment) that will be evaluated throughout visual analogical scale (VAS) from 0 to 100.
Measured: 4 hour after treatment
Secondary outcomes (4)
Efficacy at the end of treatment
Efficacy will also be evaluated based on the requirement of the study medication, if treatment has been completed during the three days (recommended in the study protocol), or on the contrary, three days of treatment have not been required due to pain remission; the requirement of rescue medication due to lack of efficacy of the prescribed treatments in the first 24 hours after the administration of the first dose. Time to rescue medication use will also be measured.
Measured: 3 days after treatment administration (72 Hours)
Correlation between efficacy and the pharmacokinetic parameters (AUC)
The efficacy of the treatments will be analyzed and whether these correlate with the pharmacokinetic parameters (AUC) for each patient, calculated from the quantified plasma concentrations of tramadol and metabolite1 of tramadol (samples 2 hour and 4h) or dexketoprofen (samples 1h and 4h).
Measured: 1 hours, 2 hours and 4 hours
Correlation between efficacy and pharmacogenetic profile (focus in CYP2D6)
The efficacy of the treatments will be analyzed with the pharmacogenetic profile of the patients, that is, if the pharmacokinetic profile, Tmax and AUC, correlates with the enzymatic activity rate for the CYP2D6 phenotype (Activity Score - AS) of poor metabolizer (AS-0), intermediate metabolizer (AS: between 0 and 1.25), normal metabolizer ( AS: between 1.25 and 2.25) or ultrarapid metabolizer (AS > 2.25)
Measured: Through study completion, an average of 1 year and 6 months
Safety evaluations
The safety evaluations will be carried out in accordance with the Good Clinical Practice Standards and current legislation. The safety of the treatments will be analyzed with the pharmacogenetic profile of the patients
Measured: Through study completion, an average of 1 year and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2022
- Study start5 Oct 2022
- Primary completion31 Aug 2026 (estimated)
- Study completion31 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-surgical 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
- Model description
- Phase IV trial and low intervention, multicenter study. Group 1: Tramadol, 100 mg according to clinical practice for the treatment of postoperative pain. Group 2: Dexketoprofen 25 mg according to clinical practice for the treatment of postoperative pain. Experimental group 3: patients in this group will be genotyped before surgery and treatment will be prescribed according to the CYP2D6 phenotype. Normal Metabolizers (NM): Tramadol 100 mg every 8 hour; Ultrarapid Metabolizers (UM): Tramadol 50 mg every 8 hours and Intermediate and poor metabolizers (IM/PM): dexketoprofen 25 mg every 8 hours
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Universitario La Paz, Hospital Universitario Ramon y Cajal, Hospital Universitario Fundación Jiménez Díaz, Hospital Universitario San Juan de Alicante, Hospital Universitario de Burgos, Hospital San Carlos, Madrid, Puerta de Hierro University Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05657704
- Sponsor's protocol ID
- 2022-500377-13-01
- Acronym
- Tradol-PriME
- Status last verified
- Aug 2026
- First submitted
- 10 Oct 2022
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No