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

Postoperative Pain Clinical Trial

— 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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05657704
• Other study ID #: 2022-500377-13-01
• Status: Recruiting
• Phase: Phase 4
• Start date: October 5, 2022
• Est. completion date: December 2023

Study information

• Verified date: December 2022
• Source: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
• Contact: Francisco Abad Santos, MD
• Phone: +34915202593
• Email: francisco.abad[@]salud.madrid.org
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Pain
• Pain, Acute
• Pain, Postoperative
• Post-surgical Pain
• Postoperative Pain

Intervention

Drug:
• The patients in experimental group will be genotyped before surgery and treatment will be prescribed according to the CYP2D6 phenotype
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

Locations

Country	Name	City	State
Spain	Hospital Universitario San Juan de Alicante	Alicante
Spain	Hospital General Universitario de Burgos y Clínica Colina	Burgos
Spain	Fundación para la Investigación Biomédica Hospital La Princesa	Madrid
Spain	Hospital Universitario Clínico San Carlos	Madrid
Spain	Hospital Universitaro La Paz	Madrid
Spain	Hospital Univesitario Ramón y Cajal	Madrid
Spain	Hostpital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid

Sponsors (8)

Lead Sponsor	Collaborator
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa	Hospital San Carlos, Madrid, Hospital Universitario de Burgos, Hospital Universitario Fundación Jiménez Díaz, Hospital Universitario La Paz, Hospital Universitario Ramon y Cajal, Hospital Universitario San Juan de Alicante, Puerta de Hierro University Hospital

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	4 hour after treatment
Secondary	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.	3 days after treatment administration (72 Hours)
Secondary	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).	1 hours, 2 hours and 4 hours
Secondary	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)	Through study completion, an average of 1 year and 6 months
Secondary	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	Through study completion, an average of 1 year and 6 months