OTC Naproxen and Acetaminophen Anti-Inflammatory Action in Dental Implant Patients
Condition: Osseointegrated Dental Implantation; Pain, Acute
MeSH terms: Acute Pain
Study type: Interventional
Phase: Phase 4

Summary: 
      This double-blind pilot study will evaluate the anti-inflammatory and analgesic effects of an
      over-the-counter (OTC) regimen of naproxen sodium versus acetaminophen in patients receiving
      one or two (adjacent) dental implants. It will also confirm that naproxen sodium in the OTC
      dosage range is a good alternative to immediate-release opioid formulations, which are
      subject to misuse, abuse and diversion in this patient population.
    

Detailed description: 
      Placement of dental implants is a frequently performed outpatient surgical procedure, with
      United States dentists currently placing implants in approximately 500,000 patients per
      year.This procedure has become the gold standard for replacing missing teeth due to its high
      level of predictability and patient acceptance, with long-term success rates greater than
      95%. Thus, the number of patients opting for this procedure over dentures and fixed bridges
      continues to increase. In the period between 1999 and 2000 only 0.7% of the USA population
      had missing teeth with implants in contrast to 5.7% between 2015 and 2016 It is estimated
      that by 2026, if the current pace of dental implant placement continues, approximately 17% of
      the population will have dental implants.

      Dental implant surgery involves the incision of gingival tissue to expose the underlying
      bone, followed by the creation of a precise bony cavity where the implant will be placed
      using a specialized surgical drill, and lastly the screwing of the implant into bone using a
      specialized handpiece Thus, it is not surprising that post-surgical pain is a common sequela
      following dental implant surgery. Patients often experience post-surgical pain for several
      days after the placement of one to three dental implants, but at a pain intensity level that
      is generally less than that of dental impaction surgery. This post-surgical pain is
      inflammatory in nature; thus, NSAIDs have demonstrated efficacy and are the preferred
      analgesics in this patient population. Postoperative administration of intranasal ketorolac
      (SPRIX®) and oral acetaminophen 325 mg plus codeine 30 mg have both demonstrated efficacy.

      The soft tissue and bony trauma associated with dental implant surgery upregulates
      inflammatory mediators both locally and systemically. Elevated levels of interleukin (IL)-6,
      IL-8, and macrophage inflammatory protein (MIP)-1β have been observed in gingival crevicular
      fluid (GCF) from the implant site and the adjacent teeth one week after surgery.
      Prostaglandin E2 has been measured in the GCF of teeth surrounding implant sites employing
      similar methodology. Additionally, standard periodontal flap and bony recontouring surgery,
      which shares many similarities to dental implant surgery, induces an upregulation in
      immunoreactive prostaglandin E2 and leukotriene B4 levels at the surgical site. Dental
      implant surgery also increases cytokine levels in plasma, indicative of a systemic
      inflammatory response. Thus, in addition to being a model to study the efficacy and
      tolerability of OTC analgesics, dental implant surgery also appears to be an excellent model
      to study the anti-inflammatory properties of NSAIDs such as naproxen sodium.

      Therefore, the investigators propose to initiate a double-blind, pilot study to evaluate the
      anti-inflammatory and analgesic effects of an OTC regimen of naproxen sodium versus
      acetaminophen in dental implant surgery patients. Notably, the vast majority of these
      patients are over the age of 45, a patient demographic that is rarely captured in
      postsurgical dental pain studies. Compared to dental impaction surgery patients, implant
      surgery patients possess more comorbidities such as hypertension, hyperlipidemia and
      hyperglycemia Thus, while dental impaction patients are typically on few if any drugs,
      polypharmacy is more of the norm in dental implant surgery patients. Performing a controlled
      study with OTC naproxen sodium in this population will provide the opportunity to confirm
      that its short-term use is generally safe and effective in these older, more medically
      complex patients. It will also confirm that naproxen sodium in the OTC dosage range is a good
      alternative to immediate-release opioid formulations, which are subject to misuse, abuse and
      diversion in this patient population.
    

Intervention name(s): Naproxen; Acetaminophen; Tramadol
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 440 mg by mouth immediately after completion of implant surgery followed by 220 mg 12 hours later.
Then 220 mg every 8 hours for the next two days.; 1000 mg by mouth immediately after the completion of implant surgery followed by 1000 mg every 6 hours for 3 days after surgery with a maximum daily dose of 3000 mg.; 50 mg by mouth every 6 hours as needed for pain
Other intervention name(s): Aleve; Extra Strength Tylenol; Ultram
Intervention MeSH terms: Acetaminophen; Naproxen; Tramadol
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double blind, randomized, active-controlled, two arms
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Naproxen sodium; Acetaminophen; Postsurgical dental pain; Prostaglandins; Tumor Necrosis Factor; Interleukins