Utility of Pharmacogenomic Testing and Postoperative Dental Pain Outcomes

• Sponsor: University of Rochester (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02932579
• Collaborator: (none)
• Enrollment: 59
• Location: 1
• Arms: 2
• Actual Duration (Months): 42.4
• Patients Per Site Per Month: 1.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pain	Other: Pharmacogenomic Testing; Drug: Ibuprofen; Drug: hydroxycontin/acetominophen; Drug: acetominophen; Drug: Oxycontin/acetominophen	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Utility of Pharmacogenomic Testing and Postoperative Dental Pain Outcomes
• Actual Study Start Date: Jul 1, 2017
• Actual Primary Completion Date: Jan 13, 2021
• Actual Study Completion Date: Jan 13, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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)	Other: Pharmacogenomic Testing; Saliva collection (5mL); Other Names: PGxOne Plus
Experimental: 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)	Other: Pharmacogenomic Testing; Saliva collection (5mL); Other Names: PGxOne Plus ; Drug: Ibuprofen; 400 mg; Drug: hydroxycontin/acetominophen; hydroxycontin 2.5 mg, acetominophen 325 mg; Other Names: Norco ; Drug: acetominophen; 650 mg; Drug: Oxycontin/acetominophen; 5mg Oxycontin, 325 mg acetominophen. This will be a rescue medication is the other three pain medications do not work.; Other Names: Percoset

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Eastman Institute for Oral Health	Rochester	New York	United States	14642

Sponsors and Collaborators

• University of Rochester

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 1, 2017
• Informed Consent Form - Jun 16, 2020

More Information

Publications

None provided.

• Responsible Party: Yanfang Ren, Professor, University of Rochester
• ClinicalTrials.gov Identifier: NCT02932579
• Other Study ID Numbers: UofREDC; RSRB00058833
• First Posted: Oct 13, 2016
• Last Update Posted: Mar 16, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Toothache; Acetaminophen; Ibuprofen; Oxycodone

Study Results

Participant Flow

Arm/Group Title	Standard of Care	Pharmacogenomic Group
Arm/Group Description	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)	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.
Period Title: Overall Study
STARTED	33	26
COMPLETED	29	25
NOT COMPLETED	4	1

Baseline Characteristics

Arm/Group Title	Standard of Care	Pharmacogenomic Group	Total
Arm/Group Description	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)	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.	Total of all reporting groups
Overall Participants	33	26	59
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	23.0 (4.2)	24.9 (4.6)	24.0 (4.0)
Sex: Female, Male (Count of Participants)
Female	20 60.6%	16 61.5%	36 61%
Male	13 39.4%	10 38.5%	23 39%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 21.2%	6 23.1%	13 22%
Not Hispanic or Latino	25 75.8%	20 76.9%	45 76.3%
Unknown or Not Reported	1 3%	0 0%	1 1.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	4 12.1%	3 11.5%	7 11.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 18.2%	10 38.5%	16 27.1%
White	18 54.5%	12 46.2%	30 50.8%
More than one race	2 6.1%	0 0%	2 3.4%
Unknown or Not Reported	3 9.1%	1 3.8%	4 6.8%
Region of Enrollment (participants) [Number]
United States	33 100%	26 100%	59 100%

Outcome Measures

1. Primary Outcome

Title	Mean Pain Score
Description	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

Outcome Measure Data

Analysis Population Description

subjects completed the study

Arm/Group Title	Standard of Care	Pharmacogenomic Group
Arm/Group Description	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)	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.
Measure Participants	29	25
Mean (Standard Deviation) [units on a scale]	41.9 (24.8)	28.9 (19.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care, Pharmacogenomic Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.098
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	13.0
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants That Did Not Need Opioid Analgesic Prescriptions
Description	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

Outcome Measure Data

Analysis Population Description

subjects completed the study

Arm/Group Title	Standard of Care	Pharmacogenomic Group
Arm/Group Description	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)	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.
Measure Participants	29	25
Count of Participants [Participants]	7 21.2%	4 15.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care, Pharmacogenomic Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.740
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.38
	Confidence Interval	(2-Sided) 95%; 0.45 to 4.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	6 hours after dosing
Adverse Event Reporting Description	any patient reported discomfort that may or may not be related to the medications during the 6 hour observation period
Arm/Group Title	Standard of Care		Pharmacogenomic Group
Arm/Group Description	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)		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.
All Cause Mortality
	Standard of Care		Pharmacogenomic Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/25 (0%)
Serious Adverse Events
	Standard of Care		Pharmacogenomic Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	Standard of Care		Pharmacogenomic Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/29 (34.5%)		7/25 (28%)
Gastrointestinal disorders
nausea	10/29 (34.5%)	10	7/25 (28%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.