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Utility of CYP2D6 Genotyping to Improve the Efficacy and Safety of Tramadol (Tradol-PriME)

Primary Purpose

Post-surgical Pain, Pain, Acute, Postoperative Pain

Status
Recruiting
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
The patients in experimental group will be genotyped before surgery and treatment will be prescribed according to the CYP2D6 phenotype
Sponsored by
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Post-surgical Pain focused on measuring Pharmacogenetics, Therapeutic techniques in treatment of acute postoperative pain

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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.

Sites / Locations

  • Hospital Universitario Puerta de Hierro
  • Hospital Universitario San Juan de Alicante
  • Hospital General Universitario de Burgos y Clínica ColinaRecruiting
  • Fundación para la Investigación Biomédica Hospital La PrincesaRecruiting
  • Hospital Univesitario Ramón y Cajal
  • Hospital Universitario Clínico San Carlos
  • Hostpital Universitario Fundación Jiménez Díaz
  • Hospital Universitaro La Paz

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

No Intervention

Experimental

Arm Label

Tramadol

Dexketoprofen

Experimental Group

Arm Description

Patients treated with Tramadol, 100 mg every 8 hours according to clinical practice for the treatment of postoperative pain.

Patients treated with Dexketoprofen 25 mg every 8 hours according to clinical practice for the treatment of postoperative pain.

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
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)
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

Full Information

First Posted
October 10, 2022
Last Updated
December 11, 2022
Sponsor
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
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
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1. Study Identification

Unique Protocol Identification Number
NCT05657704
Brief Title
Utility of CYP2D6 Genotyping to Improve the Efficacy and Safety of Tramadol
Acronym
Tradol-PriME
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.
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 5, 2022 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
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

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
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-surgical Pain, Pain, Acute, Postoperative Pain
Keywords
Pharmacogenetics, Therapeutic techniques in treatment of acute postoperative pain

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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)
Masking Description
Open label study
Allocation
Randomized
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Tramadol
Arm Type
No Intervention
Arm Description
Patients treated with Tramadol, 100 mg every 8 hours according to clinical practice for the treatment of postoperative pain.
Arm Title
Dexketoprofen
Arm Type
No Intervention
Arm Description
Patients treated with Dexketoprofen 25 mg every 8 hours according to clinical practice for the treatment of postoperative pain.
Arm Title
Experimental Group
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
The patients in experimental group will be genotyped before surgery and treatment will be prescribed according to the CYP2D6 phenotype
Other Intervention Name(s)
Tramadol 100 mg, Tramadol 50 mg, Dexketoprofen 25 mg
Intervention Description
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
Primary Outcome Measure Information:
Title
Efficacy: analgesic effect (Pain assessment) 4 hours after treatment
Description
To evaluate the analgesic effect (pain assessment) that will be evaluated throughout visual analogical scale (VAS) from 0 to 100.
Time Frame
4 hour after treatment
Secondary Outcome Measure Information:
Title
Efficacy at the end of treatment
Description
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.
Time Frame
3 days after treatment administration (72 Hours)
Title
Correlation between efficacy and the pharmacokinetic parameters (AUC)
Description
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).
Time Frame
1 hours, 2 hours and 4 hours
Title
Correlation between efficacy and pharmacogenetic profile (focus in CYP2D6)
Description
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)
Time Frame
Through study completion, an average of 1 year and 6 months
Title
Safety evaluations
Description
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
Time Frame
Through study completion, an average of 1 year and 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Francisco Abad Santos, MD
Phone
+34915202593
Email
francisco.abad@salud.madrid.org
First Name & Middle Initial & Last Name or Official Title & Degree
Jesus Novalbos Reina, PhD
Phone
+34915202540
Email
jnovalbos@iis-princesa.org
Facility Information:
Facility Name
Hospital Universitario Puerta de Hierro
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28220
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Hospital Universitario San Juan de Alicante
City
Alicante
ZIP/Postal Code
03550
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Hospital General Universitario de Burgos y Clínica Colina
City
Burgos
ZIP/Postal Code
09006
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cesar Colina Santamaría
Phone
+34 947 044 037
Email
cesar.colina@clinicacolina.com
First Name & Middle Initial & Last Name & Degree
Miriam Saiz Rodríguez, PhD
Email
msaiz@hubu.es
Facility Name
Fundación para la Investigación Biomédica Hospital La Princesa
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jesús Novalbos Reina, PhD
Phone
+34 91 520 2540
Email
jnovalbos@iis-princesa.org
First Name & Middle Initial & Last Name & Degree
Francisco Abad Santos, MD
Phone
+34 91 520 2593
Email
francisco.abad@salud.madrid.org
Facility Name
Hospital Univesitario Ramón y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Hospital Universitario Clínico San Carlos
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Individual Site Status
Active, not recruiting
Facility Name
Hostpital Universitario Fundación Jiménez Díaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dolores Martinez Pérez, MD
Email
dmartinez@fjd.es
First Name & Middle Initial & Last Name & Degree
Lucía Llanos Jiménez, MD
Email
lucia.llanos@fjd.es
Facility Name
Hospital Universitaro La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Individual Site Status
Active, not recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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Utility of CYP2D6 Genotyping to Improve the Efficacy and Safety of Tramadol

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