Clinical trial NCT03243032: Pre-Emptive Analgesia in Dental Implant Surgery
Official title: Pain Management Using Pre-Emptive Analgesia in Dental Implant Surgery - A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Pain, Postoperative
Lead sponsor: University of Iowa
Sponsor class: OTHER
First posted: 2017-08-08
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, parallel arms, double-blinded, placebo-controlled trial
Primary purpose: TREATMENT

Brief summary: To determine the clinical effectiveness of combined use of pre-emptive analgesia and long acting anesthesia for pain suppression following dental implant surgery as measured by a validated numerical rating scale and the information related to consumption of post-operative medications.

Detailed description: Dental practitioners often prescribe opioids for the relief of moderate - severe acute post-operative pain.1 There is evidence that alternative approaches, such as the use of long acting local anesthetics along with the combination of non-opioid analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), may prevent the need for opioid medications. With the current national opioid overdose epidemic, government officials have introduced new prescribing recommendations for the management of acute pain. Dentists can play a role to address this epidemic by wider recognition and adoption of the new prescribing recommendations for fast acting pre-emptive non-opioid analgesics to prevent acute dental pain.2 Dentists are the fifth leading prescribers of opioids among health care professionals accounting for 12% of the total immediate-release opioids prescribed in the United States (U.S).3 With the increasing trends of opioid prescribing for dental surgeries in the past few decades, dental implant procedures hold the highest increasing rate for opioid prescribing.4 In the U.S alone, there has been as many as 183,000 prescription opioid overdose related deaths from 1999 to 2015. Since 1999, the mortality rate from opioid overdose has more than quadrupled.5 With more than 650,000 opioid prescriptions being dispensed daily in the U.S,6 there has been a national call to alter the current prescribing patterns of opioids to ensure appropriate indications and patient selection.7 There are multiple adverse effects that may develop from opioid pain medications: nausea, vomiting, constipation, dizziness, headache.8 However, two major concerns associated with the excessive prescribing of opioids are overdosing leading to life threatening respiratory depression problems and the creation of an environment that fosters the development of opioid dependency, abuse and addiction.8 The U.S. Senate passed the 'Comprehensive Addiction and Recovery Act' of 2016 to combat the opioid epidemic.9 This legislation is designed to prevent opioid-related morbidity and misuse via physician and patient education, risk awareness, proper prescribing practices, and efforts to improve safer handling of prescription opioids.9 NSAIDs are widely used for their anti-inflammatory, pain and fever reducing properties. In the periphery, these drugs interfere with the formation of pro-inflammatory modulating prostaglandins and thromboxane A2 via reversible inhibition of the cyclooxygenase enzymes (Cox-1 and Cox-2). NSAIDs exact their effects through a variety of peripheral and central mechanisms. Their efficacy in the reduction of post-operative pain has been widely documented.10 It has been demonstrated that a single dose of an NSAID (i.e. etoricoxib, ketoprofen, diclofenac potassium, diflunisan, ibuprofen) may provide better acute post-operative analgesia than some commonly prescribed single dose opioids, even when they are prescribed in combination with other NSAIDs.10 There is also sound evidence that some individuals receive synergistic analgesic effects when NSAIDs are combined with acetaminophen.11 However, these effects can vary, as not everyone will achieve adequate pain relief even from the most potent drugs. Simple drug combinations of fast acting anti-inflammatories with acetaminophen can reliably provide successful analgesia for many acute pain patients in reasonably low doses.10 While modern dental literature contains numerous articles that support the tolerability, safety and efficacy of NSAIDs, many dental practices continue to prescribe opioids in cases which would likely respond better to other analgesics. Many dentists still underrate the risks and abuse of opioids. That is why it is important to design and test more lucid protocols for prescribing analgesics in dental care settings.

Severity of post-operative pain in periodontal and dental implant surgery can vary between mild to severe 12,13 and patient-reported outcome measures (PROMs) can be adverse at times.14 There is evidence that straightforward implant placement procedure is a surgical procedure associated with relatively low postoperative pain and pain management following dental implants is usually achieved by the use of drugs such as NSAIDs, acetaminophen, and/or opioids.11,15 Pre-emptive analgesia refers to the reduction of pain severity that occurs post-operatively by suppressing pain pre-emptively prior to the performance of the surgical procedure.16,17 Previous studies have shown the rationale and efficacy of using pre-emptive analgesia in periodontal and oral surgical models.18-25 Long acting local anesthetics such as bupivacaine have been shown to prolong the onset of and suppress postoperative pain better than lidocaine, an intermediate duration anesthetic.26,27 With successful pre-emptive analgesia including NSAIDs and long acting local anesthetics, the need for stronger post-operative analgesics, like opioids, may be significantly decreased.

Eligibility criteria: Inclusion Criteria:

* Adult patients 18 years of age and under 65 years of age
* ASA Type I \& II
* Single tooth edentulous site requiring dental implant placement without any additional bone or soft tissue augmentation at the time of implant placement
* Patients not requiring use of any form of sedation for dental implant surgery (nitrous, oral or IV sedation)

Exclusion Criteria:

* Hypersensitivity to NSAIDs, salicylates, or microcrystalline cellulose NF (Avicel PH 105)
* Liver disease
* Renal disease
* Hypertension and taking angiotensin-converting-enzyme inhibitors and/or diuretics
* Significant respiratory conditions including acute or severe asthma.
* Cardiovascular disease that will prevent the patient from going through the surgical procedure or consuming the required medications: cardiac disease, cardiomyopathy, cardiac arrhythmias, coronary heart disease, acute MI, angina, history of MI, coronary artery bypass grafting (CABG), Aspirin intake, peripheral vascular disease, cerebral vascular disease (stroke, TIA)
* Gastrointestinal disease including irritable bowel disease and gastric ulcers
* Hematological diseases (coagulopathy, hemophilia or thrombocytopenia)
* Pregnancy/lactation at the time of surgery
* Heavy smoking (\>10 cigarettes per day)
* Diabetes
* Allergies or intolerance to ibuprofen, opioids, and local anesthetic (lidocaine and bupivacaine)
* History of recreational drug abuse
* History of heavy alcohol use. Substance Abuse and Mental Health Services Administration (SAMSHA)30 defines heavy alcohol use as binge drinking on 5 or more days in the past month. SAMSHA defines binge drinking as 5 or more alcoholic drinks for males or 4 or more alcoholic drinks for females on the same occasion (i.e., at the same time or within a couple of hours of each other) on at least 1 day in the past month.
* Patients currently taking prescription pain medications or have taken over-the-counter pain medications within 4 days of surgery.
* Patients with drug-drug or drug-disease state interactions
* Other significant medical conditions (not reported above) that are likely to prevent the patient from going through the surgical procedure or consuming the required medications.

Primary outcomes:
measure: Post-operative pain as measured by numerical rating scale
timeFrame: 24 hours
Secondary outcomes:
measure: Total pain medication consumption between test and control
timeFrame: 14 days
measure: Time duration to take first pain medication between test and control
timeFrame: 14 days
measure: Post-operative pain with anterior versus posterior site of surgery
timeFrame: 24 hours
measure: Post-operative pain as it correlates with the duration of the surgical procedure
timeFrame: 24 hours
measure: Pre-surgical anxiety correlated with post-surgical pain
timeFrame: 24 hours
measure: Complications following surgery
timeFrame: 14 days
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: Univerity of Iowa College of Dentsitry Dental Clinics
state: Iowa
Study officials:
affiliation: University of Iowa College of Dentistry
name: Sathesh Elangovan, BDS
role: STUDY_DIRECTOR
References: