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

Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Status and phase: Enrolling; Phase 4

Conditions: Postoperative Pain; Pain, Acute; Post-surgical Pain

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

Study type: Interventional

Funder types: Other

Identifiers

NCT05657704

2022-500377-13-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 300 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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300 participants in 3 patient groups

Tramadol

No Intervention group

Description:

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

Dexketoprofen

No Intervention group

Description:

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

Experimental Group

Experimental group

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

Treatment:

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