Clinical trial NCT03169127: Clinical Pharmacogenetic of Ibuprofen After Lower Third Molar Surgeries
Official title: Clinical Pharmacogenetic of Ibuprofen Enantiomers After Lower Third Molar Surgeries
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Pain
Other Surgical Procedures
Impacted Third Molar Tooth
Keywords: Ibuprofen
Lower third molar
Oral Surgery
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2017-05-30
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Two Hundred healthy volunteers underwent removal of one lower third molar, will be treated to control pain, swelling and trismus with ibuprofen 600mg. Therefore, these 200 patients will be genotyped and phenotyped for these genes and their postoperative records with all data collected will be compared with the haplotypes found in the Brazilian population.
Primary purpose: SUPPORTIVE_CARE

Brief summary: The present clinical trial randomized will be to assess the link between the different haplotypes of CYP2C8 and CYP2C9 genes and the clinical efficacy of ibuprofen after lower third molar extractions. Onset, duration of postoperative analgesia, duration of anesthetic action on soft tissues, intraoperative bleeding, hemodynamic parameters, postoperative mouth opening and wound healing at the 7th postoperative day were evaluated. For this purpose, 200 healthy volunteers underwent removal of one lower third molar, under local anesthesia with articaine 4% (1:200,000 adrenaline) will be genotyped and phenotyped for these genes and their postoperative records with all data collected will be compared with the haplotypes found in the Brazilian population.

Detailed description: The aim of this study will be to assess the link between the different haplotypes of CYP2C8 and CYP2C9 genes and the clinical efficacy of ibuprofen after lower third molar extractions regarding pain, swelling and trismus, adverse reactions, the amount of pain medication used, the patient satisfaction with the drug and the influence of the ability on preoperative modulation of conditioned pain. We will evaluate also the relationship between the different haplotypes of OPRM1 gene (SNP A118G), the salivary concentrations of pro-inflammatory cytokines (IL-2, IL-4, IL-6, IL-10 and TNF-±), and preoperative conditioned pain modulation. Therefore, 200 patients will be genotyped and phenotyped for these genes and their postoperative records with all data collected will be compared with the haplotypes found in the Brazilian population.

For analysis of the proposed genes, saliva will be collected, which will serve as a source of genomic DNA. For molecular analysis it will be performed polymerase chain reaction (PCR). All tests will be conducted and validated by Applied Biosystems®. Also it will be held in the research, genetic sequencing of the genes CYP2C8, CYP2C9 and OPRM1, to verify possible correlations of these genes with postoperative pain and pain modulation.

Eligibility criteria: Inclusion Criteria:

* Need of lower third molar surgeries

Exclusion Criteria:

* Presence of systemic diseases;
* Presence of local inflammation and/or infection;
* Any history of allergic reaction to local anesthetics, gastrointestinal bleeding or ulceration;
* Cardiovascular, kidney or hepatic diseases;
* Patients who are making use of antidepressants, diuretics or anticoagulants;
* Asthma and allergy to aspirin, ibuprofen or any other nonsteroidal antiinflammatory drug;
* Regular use of any nonsteroidal antiinflammatory drug,
* Pregnancy or breast feeding.

Primary outcomes:
measure: Evaluation of changes in the postsurgical pain during the first 24 hours until 96 hours after the procedure
timeFrame: Seventh postoperative day
measure: Quality of anesthesia
timeFrame: During the surgical procedure
measure: Intraoperative bleeding during the surgeries steps
timeFrame: During the surgical procedure
measure: Blood pressure variability during the surgeries steps
timeFrame: During the surgical procedure
measure: Heart rate variability during the surgeries steps
timeFrame: During the surgical procedure
measure: Oxygen saturation variability during the surgeries steps
timeFrame: During the surgical procedure
measure: Subjective evaluation of postsurgical pain at the moment of the rescue medication utilization
timeFrame: Seventh postoperative day
Secondary outcomes:
measure: Postoperative mouth opening
timeFrame: Second and Seventh postoperative days
measure: Onset and duration of surgery after administration of local anesthetic
timeFrame: During the surgery
measure: Incidence, type and severity of adverse reactions after the surgery
timeFrame: Seventh postoperative day
measure: Total amount of rescue medication
timeFrame: Seventh postoperative day
measure: Measurement the facial edema
timeFrame: On the second day after surgery and on the seventh day after surgery.
Other outcomes:
Locations:
city: Bauru
country: Brazil
facility: University of São Paulo
state: SP
Study officials:
affiliation: 416.016.638-54
name: Giovana M Weckwerth, DDS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weckwerth GM, Dionisio TJ, Costa YM, Zupelari-Goncalves P, Oliveira GM, Torres EA, Bonjardim LR, Faria FAC, Calvo AM, Moore T, Absher DM, Santos CF. Multifocal Analysis of Acute Pain After Third Molar Removal. Front Pharmacol. 2021 Apr 15;12:643874. doi: 10.3389/fphar.2021.643874. eCollection 2021.
citation: Weckwerth GM, Dionisio TJ, Costa YM, Colombini-Ishiquiriama BL, Oliveira GM, Torres EA, Bonjardim LR, Calvo AM, Moore T, Absher DM, Santos CF. CYP450 polymorphisms and clinical pharmacogenetics of ibuprofen after lower third molar extraction. Eur J Clin Pharmacol. 2021 May;77(5):697-707. doi: 10.1007/s00228-020-03046-0. Epub 2020 Nov 17.