Towards Predicting the Analgesic Response to Ibuprofen Following Third-molar Extraction
Condition: Impacted Third Molar Tooth; Pain, Acute
MeSH terms: Acute Pain
Study type: Interventional
Phase: Phase 1

Summary: 
      This research study will evaluate inter-individual variability in the analgesic response to
      the non-steroidal anti-inflammatory drug (NSAID) ibuprofen after third molar extraction
      surgery. It will also investigate demographic, clinical, genetic, and environmental factors
      that cause this variability.
    

Detailed 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.
    

Intervention name(s): Ibuprofen; Acetaminophen; Placebo; Oxycodone
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 400 mg by mouth every 4 hours for 2 days after third molar extraction and then as needed for pain up to 7 days after third molar extraction; 500 mg by mouth every 4 hours for 2 days after third molar extraction and then as needed for pain up to 7 days after third molar extraction; By mouth; 5 mg by mouth every 6 hours as needed for pain
Other intervention name(s): Advil; Tylenol
Intervention MeSH terms: Acetaminophen; Ibuprofen; Oxycodone
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention 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)
Primary purpose: Other
Keywords: Non-steroidal anti-inflammatory drugs