PainPhase 4NCT02450487
Influence of Genotype of CYP2C9 on Clinical Efficacy and Pharmacokinetics of Piroxicam After Lower Third Molar Surgery
A Phase 4 study testing Piroxicam in people with Pain and Other Surgical Procedures, run by University of Sao Paulo.
Trial summary
Pharmacogenetics is an area of Pharmacology that studies the contribution of genetic factors to individual responses to drugs. This branch of science involves the variability in pharmacodynamics and pharmacokinetics through the study of polymorphisms in genes encoding receptors, as well as in drug metabolism, where… Read more about this study
- Who is it for?
- Ages 17 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Pain, Other Surgical Procedures, Impacted Third Molar Tooth
- What is being tested?
- Piroxicam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- No sites listed yet
- Study dates
- Oct 2012to Dec 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 17 to 60 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Impacted lower third molar;
- not making use of nonsteroidal anti-inflammatory drugs in the last 7 days;
Who cannot join
- Local anesthetics allergy;
- History of gastrointestinal bleeding or ulcers;
- Kidney disease;
- Asthma;
- Allergy or sensitivity to aspirin or any other anti-inflammatory non-steroid agent;
- Pregnant or nursing women;
- Patients using antidepressant, diuretic or aspirin;
- Patients received antibiotics for 30 days prior to surgery.
About this study
Official title: Influence of Genotype of Cytochrome P450 (CYP2C9) on Clinical Efficacy and Pharmacokinetics of Piroxicam After Lower Third Molar Surgery
Pharmacogenetics is an area of Pharmacology that studies the contribution of genetic factors to individual responses to drugs. This branch of science involves the variability in pharmacodynamics and pharmacokinetics through the study of polymorphisms in genes encoding receptors, as well as in drug metabolism, where this area of Pharmacology has been growing and achieving its first results with clinical use. The non-steroidal anti-inflammatory (NSAIDS) are metabolized by cytochrome P450 (CYP) family, predominantly CYP2C9. The goal of this study is to evaluate the different gene haplotypes for the clinical efficacy of piroxicam after third lower molar surgery for pain, edema and trismus, adverse reactions, need of rescue medication, patient satisfaction regarding the drug and the pharmacokinetics of the drug between the different gene haplotypes for CYP2C9 that are found in this population. Therefore, 60 patients will be genotyped and phenotyped for this gene and their postoperative data will be confronted with the data found in the Brazilian population. For the analysis of the proposed gene, saliva will be collected and serve as a source of genomic DNA. For the molecular analysis, polymerase chain reaction (PCR) with tests validated and produced by Applied Biosystems® will be performed. For the pharmacokinetics, saliva samples will be collected at various times according to protocols available in the literature, and piroxicam concentrations in the samples will be measured by high pressure liquid chromatography (HPLC) and Liquid chromatography-mass spectrometry (LC MS/MS). The analysis of the results will be described with a significance level of 0.05.
Read the detailed description
Lower third molars (with high degree of difficulty) surgeries will be performed in Clinical Pharmacology Laboratory at the Bauru School of Dentistry - University of São Paulo (FOB-USP), which will be provided to patients daily doses of piroxicam 20 mg 4 days. Thus collect data related to pain, swelling, trismus, amount of rescue medication required by patients, overall assessment and satisfaction about taking medicine, saliva samples for the analysis of the pharmacokinetics of the drug, genotyping and phenotyping of the subjects of the research.
The global clinical evaluation along with genotyping and phenotyping these individuals can show us if there is an influence not only in adverse effects, but also in the therapeutic effects of the drug in the Brazilian population. Research of this nature are rare in this area of Clinical Pharmacogenetics and can be of great help in prescribing these drugs to control pain and inflammation.After the removal of third molars will make collecting 6 mL of saliva in several post-surgical moments for analysis of the pharmacokinetics of the drug piroxicam and 10 mL of saliva for the analysis of genetic material. It is noteworthy that this project will initiate the nucleation of a new line of research in college, the first in Pharmacogenetics area conducted in FOB / USP.Will be assessed the following parameters in all patients after surgery of at least a third lower molar with a high degree of difficulty (Annexes 1, 2 and 3): 1) onset and duration of surgery after the administration of the local anesthetic, 2) open mouth prior to surgery, on the 2nd day after the surgery and on the 7th day after surgery (removal of stitches); 3) measured the facial edema in the second day after surgery and on the 7th day after surgery (compared to the measurements obtained before surgery); 4) body temperature before surgery, on the 2nd day after the operation and on the 7th day after surgery (removal of stitches); 5) incidence, type and severity of adverse reactions, 6) plug pain (VAS - visual analog scale) filled by patients for 4 days after prescription Piroxicam; 7) amount of rescue medication required by patients.
The comparative analysis of the data, along with data on the pharmacokinetics of the drug, genotyping and phenotyping the CYP2C9 gene, provide the basis for evaluation of the influence of the gene in clinical efficacy, side effects and need for relief medication required by patients after surgery third- molars with a high degree of difficulty, which was prescribed as anti-inflammatory piroxicam.
- Conditions
- Pain, Other Surgical Procedures, Impacted Third Molar Tooth, Cytochrome P450 CYP2C9 Enzyme Deficiency
- Being tested
- Piroxicam
- Keywords
- Piroxicam, Pharmacogenetic, Lower Third molar
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PiroxicamDrug
Also called Lower third molar surgery, Pharmacogenetics
After extraction of at least one third molar, 100 patients will be treated with Piroxicam (20 mg once daily for 4 days) for pain control, collect the saliva to be genotyped and phenotyped for CYP2C9 (by PCR) and their post-operative notes (pain, swelling, trismus, temperature) will be analyzed. For the pharmacokinetics of piroxicam saliva samples will be collected from 10 of these patients at different times after ingestion of a capsule of 20 mg Piroxicam (before, 1, 2, 3, 4, 5, 6, 8, 11, 24, 48 and 72 hours after ingestion).
| Study group | Role | What they receive |
|---|---|---|
| Interventional group | Experimental | 100 patients will be treated with Piroxicam (20 mg once daily for 4 days) for pain control after lower third molar surgery Receives: Drug: Piroxicam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Score of Pain Measured by Visual Analogue Scale
Score of pain after third molar surgery is measured by visual analogue scale (0-100mm).
Measured: at 24 hours after surgery
Secondary outcomes (1)
Number of Participants With Adverse Events
Report of adverse effects during the postoperative period until suture removal seven days after extraction of third molar included and/or impacted in patients underwent surgery.
Measured: Seven days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2015 (estimated)
- Study startOct 2012
- Primary completionOct 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- Masking
- None (open label)
- Enrolment
- 105 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, Adriana Maria Calvo, University of Sao Paulo
- Investigators
- Adriana M Calvo, PhD, Study chair, Bauru School of Dentistry/University of Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02450487
- Sponsor's protocol ID
- 20657913.7.0000.5417 CAAE
- Status last verified
- Sep 2020
- First submitted
- 15 May 2015
- Last updated
- 16 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Genotype of Cytochrome P450 (CYP2C9) on Clinical Efficacy and Pharmacokinetics of Piroxicam After Lower Third Molar Surgery
- ClinicalTrials.gov ID
- NCT02450487
- Acronym / sponsor ID
- 20657913.7.0000.5417 CAAE
- Conditions
- Pain, Other Surgical Procedures, Impacted Third Molar Tooth, Cytochrome P450 CYP2C9 Enzyme Deficiency
- Keywords
- Piroxicam, Pharmacogenetic, Lower Third molar
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Study start
- Oct 2012
- Primary completion
- Oct 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 21 May 2015 (estimated)
- Results
- Posted 16 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pharmacogenetics is an area of Pharmacology that studies the contribution of genetic factors to individual responses to drugs. This branch of science involves the variability in pharmacodynamics and pharmacokinetics through the study of polymorphisms in genes encoding receptors, as well as in drug metabolism, where this area of Pharmacology has been growing and achieving its first results with clinical use. The non-steroidal anti-inflammatory (NSAIDS) are metabolized by cytochrome P450 (CYP) family, predominantly CYP2C9. The goal of this study is to evaluate the different gene haplotypes for the clinical efficacy of piroxicam after third lower molar surgery for pain, edema and trismus, adverse reactions, need of rescue medication, patient satisfaction regarding the drug and the pharmacokinetics of the drug between the different gene haplotypes for CYP2C9 that are found in this population. Therefore, 60 patients will be genotyped and phenotyped for this gene and their postoperative data will be confronted with the data found in the Brazilian population. For the analysis of the proposed gene, saliva will be collected and serve as a source of genomic DNA. For the molecular analysis, polymerase chain reaction (PCR) with tests validated and produced by Applied Biosystems® will be performed. For the pharmacokinetics, saliva samples will be collected at various times according to protocols available in the literature, and piroxicam concentrations in the samples will be measured by high pressure liquid chromatography (HPLC) and Liquid chromatography-mass spectrometry (LC MS/MS). The analysis of the results will be described with a significance level of 0.05.
Detailed description
Lower third molars (with high degree of difficulty) surgeries will be performed in Clinical Pharmacology Laboratory at the Bauru School of Dentistry - University of São Paulo (FOB-USP), which will be provided to patients daily doses of piroxicam 20 mg 4 days. Thus collect data related to pain, swelling, trismus, amount of rescue medication required by patients, overall assessment and satisfaction about taking medicine, saliva samples for the analysis of the pharmacokinetics of the drug, genotyping and phenotyping of the subjects of the research.
The global clinical evaluation along with genotyping and phenotyping these individuals can show us if there is an influence not only in adverse effects, but also in the therapeutic effects of the drug in the Brazilian population. Research of this nature are rare in this area of Clinical Pharmacogenetics and can be of great help in prescribing these drugs to control pain and inflammation.After the removal of third molars will make collecting 6 mL of saliva in several post-surgical moments for analysis of the pharmacokinetics of the drug piroxicam and 10 mL of saliva for the analysis of genetic material. It is noteworthy that this project will initiate the nucleation of a new line of research in college, the first in Pharmacogenetics area conducted in FOB / USP.Will be assessed the following parameters in all patients after surgery of at least a third lower molar with a high degree of difficulty (Annexes 1, 2 and 3): 1) onset and duration of surgery after the administration of the local anesthetic, 2) open mouth prior to surgery, on the 2nd day after the surgery and on the 7th day after surgery (removal of stitches); 3) measured the facial edema in the second day after surgery and on the 7th day after surgery (compared to the measurements obtained before surgery); 4) body temperature before surgery, on the 2nd day after the operation and on the 7th day after surgery (removal of stitches); 5) incidence, type and severity of adverse reactions, 6) plug pain (VAS - visual analog scale) filled by patients for 4 days after prescription Piroxicam; 7) amount of rescue medication required by patients.
The comparative analysis of the data, along with data on the pharmacokinetics of the drug, genotyping and phenotyping the CYP2C9 gene, provide the basis for evaluation of the influence of the gene in clinical efficacy, side effects and need for relief medication required by patients after surgery third- molars with a high degree of difficulty, which was prescribed as anti-inflammatory piroxicam.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Interventional group | Experimental | Drug: Piroxicam100 patients will be treated with Piroxicam (20 mg once daily for 4 days) for pain control after lower third molar surgery |
Who may qualify
- Ages
- 17 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Impacted lower third molar;
- not making use of nonsteroidal anti-inflammatory drugs in the last 7 days;
Key exclusion criteria (8 listed)
- Local anesthetics allergy;
- History of gastrointestinal bleeding or ulcers;
- Kidney disease;
- Asthma;
- Allergy or sensitivity to aspirin or any other anti-inflammatory non-steroid agent;
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 |
|---|---|---|
| PiroxicamAlso: Lower third molar surgery, PharmacogeneticsAfter extraction of at least one third molar, 100 patients will be treated with Piroxicam (20 mg once daily for 4 days) for pain control, collect the saliva to be genotyped and phenotyped for CYP2C9 (by PCR) and their post-operative notes (pain, swelling, trismus, temperature) will be analyzed. For the pharmacokinetics of piroxicam saliva samples will be collected from 10 of these patients at different times after ingestion of a capsule of 20 mg Piroxicam (before, 1, 2, 3, 4, 5, 6, 8, 11, 24, 48 and 72 hours after ingestion). | Drug | Interventional group |
Primary outcome
Score of Pain Measured by Visual Analogue Scale
Time frame: at 24 hours after surgery
Score of pain after third molar surgery is measured by visual analogue scale (0-100mm).
1 secondary outcome
Number of Participants With Adverse Events
Time frame: Seven days after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Adriana M Calvo, PhD study chair
Bauru School of Dentistry/University of Sao Paulo
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Piroxicam in people with Pain and Other Surgical Procedures, run by University of Sao Paulo.
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 2 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: finished, as of the sponsor's last update on 16 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
Yes. Results are posted in the registry (first posted 16 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Score of Pain Measured by Visual Analogue Scale (time frame: at 24 hours after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Sep 2020.