Clinical trial NCT05657704: Utility of CYP2D6 Genotyping to Improve the Efficacy and Safety of Tramadol
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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Post-surgical Pain
Pain, Acute
Postoperative Pain
Keywords: Pharmacogenetics
Therapeutic techniques in treatment of acute postoperative pain
Lead sponsor: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Sponsor class: OTHER
Collaborators: name: Hospital Universitario La Paz
name: Hospital Universitario Ramon y Cajal
name: Hospital Universitario Fundación Jiménez Díaz
name: Hospital Universitario San Juan de Alicante
name: Hospital Universitario de Burgos
name: Hospital San Carlos, Madrid
name: Puerta de Hierro University Hospital
First posted: 2022-12-20
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Efficacy: analgesic effect (Pain assessment) 4 hours after treatment
timeFrame: 4 hour after treatment
Secondary outcomes:
measure: Efficacy at the end of treatment
timeFrame: 3 days after treatment administration (72 Hours)
measure: Correlation between efficacy and the pharmacokinetic parameters (AUC)
timeFrame: 1 hours, 2 hours and 4 hours
measure: Correlation between efficacy and pharmacogenetic profile (focus in CYP2D6)
timeFrame: Through study completion, an average of 1 year and 6 months
measure: Safety evaluations
timeFrame: Through study completion, an average of 1 year and 6 months
Other outcomes:
Locations:
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
state: Madrid
city: Alicante
country: Spain
facility: Hospital Universitario San Juan de Alicante
city: Burgos
country: Spain
facility: Hospital General Universitario de Burgos y Clínica Colina
city: Madrid
country: Spain
facility: Fundación para la Investigación Biomédica Hospital La Princesa
city: Madrid
country: Spain
facility: Hospital Univesitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos
city: Madrid
country: Spain
facility: Hostpital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitaro La Paz
Study officials:
References: