Towards Predicting the Analgesic Response to Ibuprofen Following Third-molar Extraction

Last updated on July 2021

Recruitment

Recruitment Status: Recruiting
Estimated Enrollment: Same as current

Summary

Conditions

Impacted Third Molar Tooth
Pain Acute

Type

Interventional

Phase

Phase 1

Design

Allocation: RandomizedIntervention Model: Parallel AssignmentIntervention Model Description: Subjects will be randomized to receive either ibuprofen or placebo after third molar extraction when pain intensity is at least 4/10. Four hours after the masked ibuprofen or placebo, all subjects will receive open-label ibuprofen + acetaminophen to be taken every 4 hours for the first 2 days and then as needed for up to 7 days after oral surgery. Oxycodone will be available as a rescue medication if additional analgesic is requested.Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Masking Description: Administration of ibuprofen vs. placebo will be masked.Primary Purpose: Other

Participation Requirements

Age: Between 18 years and 64 years
Gender: Both males and females

Description

The dramatic increase in opioid prescriptions over the past years has been linked to the concomitant rise in opioid addiction and to deaths from opioid abuse. Young adults' initial exposure to opioid analgesics is often following extraction of their impacted third molars, with an average of 5,000,000 cases in the USA per year. Over-prescribing of opioids for surgical pain, often 2-5 times more than patients actually use, further exacerbates this problem, as patients tend to save leftover pills rather than discard them. Up to 70% of individuals who become addicted to prescription opioids had access to leftover pills prescribed for others. This is particularly troubling as the odds of transitioning to heroin from prescription opioid abuse are much higher than other suspected gateway drugs, about 40 fold greater than non-gateway drug users. Heroin is now often laced with fentanyl derivatives making overdose and death more likely in even the most opioid tolerant individuals. Multiple studies have demonstrated that non-addicting nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and diclofenac are effective in relieving pain after dental impaction surgery, being at least equally efficacious to optimal doses of immediate release opioid formulations combined with acetaminophen. However, these assessments of pain relief represent average scores and approximately 22% and 50% of individuals required additional opioid-containing rescue analgesics when ibuprofen and diclofenac were employed at FDA-approved dosages. A deeper understanding of the sources of variability in pain relief should allow improvements in the overall efficacy of NSAIDs by targeting treatment to those who are most likely to receive sufficient pain relief. Thus, optimizing pain therapy with NSAIDs by personalization would be expected to help limit the unnecessary prescription of highly addicting immediate release opioids. Moreover, these results may have applicability to other types of pain that are driven by inflammation.

Tracking Information

NCT #: NCT03893175
Collaborators: Not Provided
Investigators: Principal Investigator: Tilo Grosser, MD University of Pennsylvania Principal Investigator: Katherine N Theken, PharmD, PhD University of Pennsylvania Principal Investigator: Elliot V Hersh, DMD, MS, PhD University of Pennsylvania Principal Investigator: John Farrar, MD, PhD University of Pennsylvania