Pain
Conditions
Brief summary
Opioid analgesics are the most common postoperative pain medications used among dentists in the United States.Although these medications are highly effective in the postoperative dental pain management, not all patients optimally benefit from this therapy. Many suffer adverse consequences such as nausea, emesis, and psychomotor impairment, and there is a high prevalence of opioid prescription misuse among substance abusers within the dental patient population. The use of non-opioid analgesics including ibuprofen and acetaminophen in the management of postoperative dental pain has demonstrated equivalent or superior analgesic effects compared to opioid analgesic therapies, typically with significantly less adverse effects.However, despite these results, dentists have encountered a high variability in the success of non-opioid analgesic responses among the postoperative dental pain population.Thus, new strategies for earlier recognition of analgesic responses for pain medications is fundamental in the field of dentistry. Therefore, this study will evaluate the clinical utility of pharmacogenomic testing in acute postoperative dental pain management among healthy adults who undergo extraction of impacted mandibular third molar.
Detailed description
To date, the use of pharmacogenomic methods in medicine has broadened our understanding of the important role of genes and different phenotypes/genotypes that make each individual unique in pain responses, including drug biotransformation, transportation, and drug-related side effects to name a few.Thus, recognizing the genetic profile of each individual prior to the prescription of pain medication for postoperative dental pain management will be essential to provide a more effective and safer pain therapy.Additionally, we suggest that 80% of the individuals in the general population exhibit a genetic profile that influence a normal pain response to non-opioid pain therapies. Hence we postulate that the integration of a pharmacogenomic testing to guide the prescription of ibuprofen and acetaminophen, not only, could lead to improved clinical postoperative dental pain outcomes, but also, significantly reduce opioid analgesics prescriptions by dentists.
Interventions
Saliva collection (5mL)
DRUGIbuprofen
400 mg
DRUGhydroxycontin/acetominophen
hydroxycontin 2.5 mg, acetominophen 325 mg
DRUGacetominophen
650 mg
DRUGOxycontin/acetominophen
5mg Oxycontin, 325 mg acetominophen. This will be a rescue medication is the other three pain medications do not work.
Sponsors
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Patients who are able to read, comprehend, and sign the consent form, and willing to stay in the study unit for up to 12 hours. * Patients who are reliable, cooperative, and of adequate intelligence to record the requested information on the questionnaire form(s). * Women of childbearing potential who are not pregnant, as assessed by a urine pregnancy quick test on the day of the procedure, prior to surgery. Women must be using a method of birth control deemed acceptable by the investigator and continue to use this method during the duration of dosing with study medication * Patient who develop sufficient levels of pain (rated at 50mm or more out of a 100 mm) on the DPIS within 6 hours post-surgical extraction. * Patients who agree not to take analgesics other than protocol-defined rescue analgesics during the post-operative treatment period of 6 hours. * Patients who agree to refrain from alcohol and sedative consumption during the post-operative period of 6 hours. * Patients scheduled to undergo surgical removal of 3 or more impacted third molars, at least 1 of which must be a bony mandibular impaction. In addition, the sum of the dental impaction scores must be 9 or above, carried out by investigator.
Exclusion criteria
Subjects with: * Known opioids and NSAIDs allergies (or induced asthmatic attacks) * Known history of opioid abuse * Recent history of gastrointestinal ulceration * History of aspirin intolerance/cross-sensitivity * Recent myocardial disease * Uncontrolled hypertension * Patients receiving anticoagulation therapy * Uncontrolled diabetes * Pregnant women * Immunosuppression * Recent history of opioid or NSAID therapies * Subjects who do not achieve a qualifying baseline pain threshold of 50mm out of 100mm on the visual analog DIPS within 6 hours of completion of surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Pain Score | 6 hours | To compare the pain control outcomes between a single-dose of pharmacogenomics- testing-driven-prescription of ibuprofen (400mg) or acetaminophen (650mg) with those of single-dose (standard of care) of combined formulation of hydrocodone and acetaminophen (5/650mg). A visual analog scale for dental pain will be used. Scale ranges from 0-100 with 100 worse pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Did Not Need Opioid Analgesic Prescriptions | 6 hours | To determine the number of patients who did not require prescribed opioid analgesic'rescue' after pharmacogenomic-guided acute postoperative dental pain management versus those taking the non-guided combined formulation of hydrocodone and acetaminophen. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care Individuals within this group will receive standard of care for postoperative dental pain secondary to extraction of impacted mandibular third molar(s)
Pharmacogenomic Testing: Saliva collection (5mL) | 33 |
| Pharmacogenomic Group Individuals within this group will receive pharmacogenomic testing guided prescription of pain medication for postoperative dental pain secondary to extraction of impacted mandibular third molar(s)
Pharmacogenomic Testing: Saliva collection (5mL)
Ibuprofen: 400 mg
hydroxycontin/acetominophen: hydroxycontin 2.5 mg, acetominophen 325 mg
acetominophen: 650 mg
Oxycontin/acetominophen: 5mg Oxycontin, 325 mg acetominophen. This will be a rescue medication is the other three pain medications do not work. | 26 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Standard of Care | Total | Pharmacogenomic Group |
|---|---|---|---|
| Age, Continuous | 23.0 years STANDARD_DEVIATION 4.2 | 24.0 years STANDARD_DEVIATION 4 | 24.9 years STANDARD_DEVIATION 4.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 13 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 45 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 16 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) White | 18 Participants | 30 Participants | 12 Participants |
| Region of Enrollment United States | 33 participants | 59 participants | 26 participants |
| Sex: Female, Male Female | 20 Participants | 36 Participants | 16 Participants |
| Sex: Female, Male Male | 13 Participants | 23 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 25 |
| other Total, other adverse events | 10 / 29 | 7 / 25 |
| serious Total, serious adverse events | 0 / 29 | 0 / 25 |
Outcome results
Primary
Mean Pain Score
To compare the pain control outcomes between a single-dose of pharmacogenomics- testing-driven-prescription of ibuprofen (400mg) or acetaminophen (650mg) with those of single-dose (standard of care) of combined formulation of hydrocodone and acetaminophen (5/650mg). A visual analog scale for dental pain will be used. Scale ranges from 0-100 with 100 worse pain.
Time frame: 6 hours
Population: subjects completed the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care | Mean Pain Score | 41.9 units on a scale | Standard Deviation 24.8 |
| Pharmacogenomic Group | Mean Pain Score | 28.9 units on a scale | Standard Deviation 19.4 |
p-value: 0.098t-test, 2 sided
Secondary
Number of Participants That Did Not Need Opioid Analgesic Prescriptions
To determine the number of patients who did not require prescribed opioid analgesic'rescue' after pharmacogenomic-guided acute postoperative dental pain management versus those taking the non-guided combined formulation of hydrocodone and acetaminophen.
Time frame: 6 hours
Population: subjects completed the study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care | Number of Participants That Did Not Need Opioid Analgesic Prescriptions | 7 Participants |
| Pharmacogenomic Group | Number of Participants That Did Not Need Opioid Analgesic Prescriptions | 4 Participants |
p-value: 0.7495% CI: [0.45, 4.21]Fisher Exact