PainPhase 4NCT03169127
Clinical Pharmacogenetic of Ibuprofen After Lower Third Molar Surgeries
A Phase 4 study testing Ibuprofen 600 mg in people with Pain and Other Surgical Procedures, run by University of Sao Paulo at 1 site in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Pain, Other Surgical Procedures, Impacted Third Molar Tooth
- What is being tested?
- Ibuprofen 600 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteBrazil
- Study dates
- 1 Apr 2016to 1 Jul 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Need of lower third molar surgeries
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Pharmacogenetic of Ibuprofen Enantiomers After Lower Third Molar Surgeries
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.
Read the 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.
- Conditions
- Pain, Other Surgical Procedures, Impacted Third Molar Tooth
- Being tested
- Ibuprofen 600 mg
- Keywords
- Ibuprofen, Lower third molar, Oral Surgery
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ibuprofen 600 mgDrug
Also called Lower third molar surgery with ibuprofen for pharmacogenetic
After lower third molars surgeries, pharmacogenetic and clinical efficacy of Ibuprofen 600mg was study.
| Study group | Role | What they receive |
|---|---|---|
| Experimental Group Ibuprofen 600mg | Experimental | 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. Receives: Drug: Ibuprofen 600 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of changes in the postsurgical pain during the first 24 hours until 96 hours after the procedure
Subjective evaluation of postsurgical pain, which was annotated by the volunteer after the surgery, in a Visual Analogue Scale (VAS, 0-100 mm). The subjective pain evaluations will be performed by patients at the following times after administration of the drug [0, 15, 30 and 45 min, 1; 1.5; 2; 3; 4; 5; 6; 7; 8; 10; 12; 16; 24 hr, 48, 72 and 96 h]. What will be taken into account on this outcome is the representation of the postsurgical pain, that will be noted on the Visual Analogue Scale (in millimeters) in respective moments.
Measured: Seventh postoperative day
Quality of anesthesia
Quality of anesthesia during surgery based on a category 3point scale: 1) the patient reported no discomfort; 2) the patient reported discomfort, without the need to supplement the anesthesia; 3) reported some discomfort by the patient, requiring anesthesia complementation. Intraoral bleeding that will be evaluated by the surgeon according to a 3point scale (1: minimal, 2: normal and 3: Maximum), immediately after the following steps: injection of the first cartridge anesthesia, incision, mucoperiosteal detachment, osteotomies, tooth section, extraction, cleaning and suturing.
Measured: During the surgical procedure
Intraoperative bleeding during the surgeries steps
Intraoperative bleeding, rated by the surgeon according to a 3 point category rating scale (1 minimal bleeding; 2 normal bleeding; 3 excessive bleeding) (SISK, 1986), immediately after the following steps: injection of the first cartridge of articaine, tissue incision, flap reflection, bone removal (when this procedure was necessary), tooth extraction, cleaning of the operated site, and completion of suturing.
Measured: During the surgical procedure
Blood pressure variability during the surgeries steps
Systolic blood pressure, diastolic, and mean to be verified and recorded at surgical moments previously described (injection of the first cartridge anesthesia, incision, mucoperiosteal detachment, osteotomies, tooth section, extraction, cleaning and suturing), carried out with the aid of a system for monitoring hemodynamic parameters.
Measured: During the surgical procedure
Heart rate variability during the surgeries steps
Heart rate to be verified and recorded surgical at moments described above, carried out with the aid of a system for monitoring hemodynamic parameters.
Measured: During the surgical procedure
Oxygen saturation variability during the surgeries steps
Oxygen saturation to be verified and recorded at surgical moments described above, carried out with the aid of a system for monitoring hemodynamic parameters.
Measured: During the surgical procedure
Subjective evaluation of postsurgical pain at the moment of the rescue medication utilization
Subjective evaluation of postsurgical pain at the moment of the rescue medication consumption which was annotated by the volunteer after the surgery, in a Visual Analogue Scale (VAS, 0-100 mm).
Measured: Seventh postoperative day
Secondary outcomes (5)
Postoperative mouth opening
Mouth opening (mm) between the mesial-incisal corners of the upper and lower right central incisors at maximum opening of the jaws was measured and recorded before the surgery and during the second and seventh postoperative days.
Measured: Second and Seventh postoperative days
Onset and duration of surgery after administration of local anesthetic
Will only be considered those surgeries in which there is no difference in the duration time of the procedure between the patients. This time count will be started after the administration of the first local anesthetic. Unit of mesure used will be hours.
Measured: During the surgery
Incidence, type and severity of adverse reactions after the surgery
Will be considered as adverse reactions: gastrointestinal irritation, nausea, vomiting, bleeding, allergy, headache, dizziness, drowsiness or any other type of reaction presented after surgery.
Measured: Seventh postoperative day
Total amount of rescue medication
The total amount of rescue medication that was used by the patient during the postoperative period (Acetominophen- 750 mg) will be analyzed.
Measured: Seventh postoperative day
Measurement the facial edema
It will apply the method used by Ustun et al. (2003), which takes into account the sum of the following measures (obtained with flexible tape measure): A) distance between the lateral corner of the eye and the gonion, B) away from the tragus corner of the mouth and C) away from the tragus to the soft tissue of pogonion. Preoperative sum of three measures will be considered as the baseline that way. The difference between the values obtained in the postoperative period and baseline indicate the facial edema in the 2nd and 7th days.
Measured: On the second day after surgery and on the seventh day after surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2017
- Study start1 Apr 2016
- Primary completion30 Jul 2018
- Study completion1 Jul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by University of Sao PauloThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- 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.
- Masking
- None (open label)
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Responsible party
- Principal investigator, Giovana Maria Weckwerth, University of Sao Paulo
- Investigators
- Giovana M Weckwerth, DDS, Principal investigator, 416.016.638-54
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03169127
- Sponsor's protocol ID
- 59807716.9.0000.5417
- Status last verified
- Jul 2019
- First submitted
- 16 Mar 2017
- Last updated
- 12 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33935738Weckwerth 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.
PubMed 33205280
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Pharmacogenetic of Ibuprofen Enantiomers After Lower Third Molar Surgeries
- ClinicalTrials.gov ID
- NCT03169127
- Acronym / sponsor ID
- 59807716.9.0000.5417
- Conditions
- Pain, Other Surgical Procedures, Impacted Third Molar Tooth
- Keywords
- Ibuprofen, Lower third molar, Oral Surgery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (actual)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Study start
- 1 Apr 2016 (actual)
- Primary completion
- 30 Jul 2018 (actual)
- Study completion
- 1 Jul 2020 (estimated)
- First posted
- 30 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Experimental Group Ibuprofen 600mg | Experimental | Drug: Ibuprofen 600 mgTwo 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Need of lower third molar surgeries
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ibuprofen 600 mgAlso: Lower third molar surgery with ibuprofen for pharmacogeneticAfter lower third molars surgeries, pharmacogenetic and clinical efficacy of Ibuprofen 600mg was study. | Drug | Experimental Group Ibuprofen 600mg |
Primary outcome
Evaluation of changes in the postsurgical pain during the first 24 hours until 96 hours after the procedure
Time frame: Seventh postoperative day
Subjective evaluation of postsurgical pain, which was annotated by the volunteer after the surgery, in a Visual Analogue Scale (VAS, 0-100 mm). The subjective pain evaluations will be performed by patients at the following times after administration of the drug [0, 15, 30 and 45 min, 1; 1.5; 2; 3; 4; 5; 6; 7; 8; 10; 12; 16; 24 hr, 48, 72 and 96 h]. What will be taken into account on this outcome is the representation of the postsurgical pain, that will be noted on the Visual Analogue Scale (in millimeters) in respective moments.
Quality of anesthesia
Time frame: During the surgical procedure
Quality of anesthesia during surgery based on a category 3point scale: 1) the patient reported no discomfort; 2) the patient reported discomfort, without the need to supplement the anesthesia; 3) reported some discomfort by the patient, requiring anesthesia complementation. Intraoral bleeding that will be evaluated by the surgeon according to a 3point scale (1: minimal, 2: normal and 3: Maximum), immediately after the following steps: injection of the first cartridge anesthesia, incision, mucoperiosteal detachment, osteotomies, tooth section, extraction, cleaning and suturing.
Intraoperative bleeding during the surgeries steps
Time frame: During the surgical procedure
Intraoperative bleeding, rated by the surgeon according to a 3 point category rating scale (1 minimal bleeding; 2 normal bleeding; 3 excessive bleeding) (SISK, 1986), immediately after the following steps: injection of the first cartridge of articaine, tissue incision, flap reflection, bone removal (when this procedure was necessary), tooth extraction, cleaning of the operated site, and completion of suturing.
Blood pressure variability during the surgeries steps
Time frame: During the surgical procedure
Systolic blood pressure, diastolic, and mean to be verified and recorded at surgical moments previously described (injection of the first cartridge anesthesia, incision, mucoperiosteal detachment, osteotomies, tooth section, extraction, cleaning and suturing), carried out with the aid of a system for monitoring hemodynamic parameters.
Heart rate variability during the surgeries steps
Time frame: During the surgical procedure
Heart rate to be verified and recorded surgical at moments described above, carried out with the aid of a system for monitoring hemodynamic parameters.
Oxygen saturation variability during the surgeries steps
Time frame: During the surgical procedure
Oxygen saturation to be verified and recorded at surgical moments described above, carried out with the aid of a system for monitoring hemodynamic parameters.
Subjective evaluation of postsurgical pain at the moment of the rescue medication utilization
Time frame: Seventh postoperative day
Subjective evaluation of postsurgical pain at the moment of the rescue medication consumption which was annotated by the volunteer after the surgery, in a Visual Analogue Scale (VAS, 0-100 mm).
5 secondary outcomes
Postoperative mouth opening
Time frame: Second and Seventh postoperative days
Onset and duration of surgery after administration of local anesthetic
Time frame: During the surgery
Incidence, type and severity of adverse reactions after the surgery
Time frame: Seventh postoperative day
Total amount of rescue medication
Time frame: Seventh postoperative day
Measurement the facial edema
Time frame: On the second day after surgery and on the seventh day after surgery.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2019.
- Derived from this study: PubMed 33935738Weckwerth 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.
- Derived from this study: PubMed 33205280Weckwerth 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giovana M Weckwerth, DDS principal investigator
416.016.638-54
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ibuprofen 600 mg in people with Pain and Other Surgical Procedures, run by University of Sao Paulo at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of changes in the postsurgical pain during the first 24 hours until 96 hours after the procedure (time frame: Seventh postoperative day). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03169127, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2019.