OTC Naproxen and Acetaminophen Anti-Inflammatory Action in Dental Implant Patients

NCT04694300 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: 844440IIR
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Osseointegrated Dental Implantation; Pain, Acute

Keywords

Naproxen sodium; Acetaminophen; Postsurgical dental pain; Prostaglandins; Interleukins

Outcome Measures

Primary Outcomes (4)

• Pain Intensity Scores on Numeric Pain Intensity Scale 0-6 Hours

  Median maximum pain intensity scores where 0 = no pain and 10 = worst possible pain

  Up to 6 hours

• Pain Intensity Scores From 6 Through 72 Hours (Multi-dose Phase)

  Pain intensity scores where 0 = no pain and 10 = worst possible pain

  6-72 hours Post initial Dose

• Peak Plasma IL-6 Concentrations

  Plasma IL-6 concentrations 6 hours after treatment measured by ELISA

  6 hours

• Plasma IL-6 Change From Baseline

  Percent change in plasma IL-6 levels at 6 hours after treatment relative to baseline

  6 hours post dose

Secondary Outcomes (6)

• Rescue Analgesic Use

  0-6 hours

• Rescue Medication Use Outpatient Phase (6-72 Hours)

  6-72 hours

• Peak GCF IL-1β Levels

  24 hours post-dose

• COX-1 Activity Percent of Baseline (Pre-surgery)

  6 hours post dose

• COX-2 Activity

  6 hours post-dose

Study Arms (2)

Naproxen sodium

EXPERIMENTAL

Naproxen sodium 440 mg followed by naproxen sodium 220 mg q 8h (max 660 mg/day)

Drug: Naproxen; Drug: Tramadol

Acetaminophen

ACTIVE COMPARATOR

Acetaminophen 1000 mg followed by acetaminophen 1000 mg q 6h (max 3000 mg/day according to Tylenol package insert)

Drug: Acetaminophen; Drug: Tramadol

Interventions

Naproxen DRUG

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.

Also known as: Aleve

Naproxen sodium

Acetaminophen DRUG

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.

Also known as: Extra Strength Tylenol

Acetaminophen

Tramadol DRUG

50 mg by mouth every 6 hours as needed for pain

Also known as: Ultram

Acetaminophen; Naproxen sodium

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject requires surgical placement of one or two (adjacent) dental implants
• Ability to read and sign informed consent
• Males and females for 18-75 years of age
• Non-smokers
• Negative urine drug screen

You may not qualify if:

• Advanced periodontal disease (\>20% Clinical Attachment Loss \>20% radiographic bone loss)
• History of bisphosphonate usage
• Medical history or medical condition that makes any of the study medications (naproxen sodium, acetaminophen, tramadol, etc.) inappropriate treatment options including any scheduled or recent cardiac procedures (within 6 months), a history of GI ulcers, liver or kidney disease, and anticoagulant or lithium intake.
• History of an allergic reaction to any pain reliever/fever reducer
• Contraindication to opioid use
• Positive urine drug screen for drugs of abuse unless on stable doses of a non-analgesic drug for a legitimate medical purpose
• Pregnancy - A urine pregnancy test will be performed immediately before the scheduled surgery on all women of child-bearing potential
• Local or systemic diseases that affects wound healing and inflammatory biomarkers (diabetes, autoimmune (rheumatoid arthritis), or inflammatory disorders - osteoarthritis is allowed).
• Smokers on this pilot study because it can affect levels of inflammatory biomarkers - a urine cotinine test will be performed immediately prior to the scheduled surgery on all subjects even if participant denies smoking history
• History of systemic steroid use over 2 weeks within last 2 years.
• Poor oral hygiene on a non-compliant individual.

Sponsors & Collaborators

• Hersh, Elliot V., DMD, MS, PhD: lead
• University of Pennsylvania: collaborator

Study Sites (1)

University of Pennsylvania School of Dental Medicine

Philadelphia, Pennsylvania, 19104-6030, United States

Location

Related Publications (18)

• Moore PA, Hersh EV. Combining ibuprofen and acetaminophen for acute pain management after third-molar extractions: translating clinical research to dental practice. J Am Dent Assoc. 2013 Aug;144(8):898-908. doi: 10.14219/jada.archive.2013.0207.

  PMID: 23904576 BACKGROUND

• Hersh EV, Moore PA, Grosser T, Polomano RC, Farrar JT, Saraghi M, Juska SA, Mitchell CH, Theken KN. Nonsteroidal Anti-Inflammatory Drugs and Opioids in Postsurgical Dental Pain. J Dent Res. 2020 Jul;99(7):777-786. doi: 10.1177/0022034520914254. Epub 2020 Apr 14.

  PMID: 32286125 BACKGROUND

• Deeb GR, Deeb JG, Agarwal V, Laskin DM. Use of transalveolar sutures to maintain vestibular depth and manipulate keratinized tissue following alveolar ridge reduction and implant placement for mandibular prosthesis. J Oral Maxillofac Surg. 2015 Jan;73(1):48-52. doi: 10.1016/j.joms.2014.07.022. Epub 2014 Jul 30.

  PMID: 25315314 BACKGROUND

• Schmitt A, Zarb GA. The longitudinal clinical effectiveness of osseointegrated dental implants for single-tooth replacement. Int J Prosthodont. 1993 Mar-Apr;6(2):197-202.

  PMID: 8329098 BACKGROUND

• Zarb GA, Schmitt A. The longitudinal clinical effectiveness of osseointegrated dental implants in posterior partially edentulous patients. Int J Prosthodont. 1993 Mar-Apr;6(2):189-96.

  PMID: 8329097 BACKGROUND

• Elani HW, Starr JR, Da Silva JD, Gallucci GO. Trends in Dental Implant Use in the U.S., 1999-2016, and Projections to 2026. J Dent Res. 2018 Dec;97(13):1424-1430. doi: 10.1177/0022034518792567. Epub 2018 Aug 3.

  PMID: 30075090 BACKGROUND

• Bockow R, Korostoff J, Pinto A, Hutcheson M, Secreto SA, Bodner L, Hersh EV. Characterization and treatment of postsurgical dental implant pain employing intranasal ketorolac. Compend Contin Educ Dent. 2013 Sep;34(8):570-6.

  PMID: 24564610 BACKGROUND

• Alissa R, Sakka S, Oliver R, Horner K, Esposito M, Worthington HV, Coulthard P. Influence of ibuprofen on bone healing around dental implants: a randomised double-blind placebo-controlled clinical study. Eur J Oral Implantol. 2009 Autumn;2(3):185-99.

  PMID: 20467629 BACKGROUND

• Hashem AA, Claffey NM, O'Connell B. Pain and anxiety following the placement of dental implants. Int J Oral Maxillofac Implants. 2006 Nov-Dec;21(6):943-50.

  PMID: 17190305 BACKGROUND

• Al-Khabbaz AK, Griffin TJ, Al-Shammari KF. Assessment of pain associated with the surgical placement of dental implants. J Periodontol. 2007 Feb;78(2):239-46. doi: 10.1902/jop.2007.060032.

  PMID: 17274712 BACKGROUND

• Samieirad S, Afrasiabi H, Tohidi E, Qolizade M, Shaban B, Hashemipour MA, Doaltian Shirvan I. Evaluation of caffeine versus codeine for pain and swelling management after implant surgeries: A triple blind clinical trial. J Craniomaxillofac Surg. 2017 Oct;45(10):1614-1621. doi: 10.1016/j.jcms.2017.06.014. Epub 2017 Jul 5.

  PMID: 28864284 BACKGROUND

• Emecen-Huja P, Eubank TD, Shapiro V, Yildiz V, Tatakis DN, Leblebicioglu B. Peri-implant versus periodontal wound healing. J Clin Periodontol. 2013 Aug;40(8):816-24. doi: 10.1111/jcpe.12127. Epub 2013 Jun 18.

  PMID: 23772674 BACKGROUND

• Aboyoussef H, Carter C, Jandinski JJ, Panagakos FS. Detection of prostaglandin E2 and matrix metalloproteinases in implant crevicular fluid. Int J Oral Maxillofac Implants. 1998 Sep-Oct;13(5):689-96.

  PMID: 9796154 BACKGROUND

• O'Brien TP, Roszkowski MT, Wolff LF, Hinrichs JE, Hargreaves KM. Effect of a non-steroidal anti-inflammatory drug on tissue levels of immunoreactive prostaglandin E2, immunoreactive leukotriene, and pain after periodontal surgery. J Periodontol. 1996 Dec;67(12):1307-16. doi: 10.1902/jop.1996.67.12.1307.

  PMID: 8997678 BACKGROUND

• Li S, Yang Y, Yu C, Yao Y, Wu Y, Qian L, Cheung CW. Dexmedetomidine Analgesia Effects in Patients Undergoing Dental Implant Surgery and Its Impact on Postoperative Inflammatory and Oxidative Stress. Oxid Med Cell Longev. 2015;2015:186736. doi: 10.1155/2015/186736. Epub 2015 Jun 15.

  PMID: 26171113 BACKGROUND

• Pietruski JK, Pietruska MD, Stokowska W, Pattarelli GM. Serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and interleukin-8 (IL-8) in patients treated with dental implants. Rocz Akad Med Bialymst. 2001;46:28-37.

  PMID: 11780571 BACKGROUND

• Aghaloo T, Pi-Anfruns J, Moshaverinia A, Sim D, Grogan T, Hadaya D. The Effects of Systemic Diseases and Medications on Implant Osseointegration: A Systematic Review. Int J Oral Maxillofac Implants. 2019 Suppl;34:s35-s49. doi: 10.11607/jomi.19suppl.g3.

  PMID: 31116832 BACKGROUND

• Theken KN, Chen M, Wall DL, Pham T, Secreto SA, Yoo TH, Rascon AN, Chang YC, Korostoff JM, Mitchell CH, Hersh EV. A randomized, double-blind pilot study of analgesic and anti-inflammatory effects of naproxen sodium and acetaminophen following dental implant placement surgery. Front Pharmacol. 2023 May 17;14:1199580. doi: 10.3389/fphar.2023.1199580. eCollection 2023.

  PMID: 37266144 RESULT

Related Links

• 17 Dental Implant Industry Statistics and Trends.

MeSH Terms

Conditions

Acute Pain

Interventions

Naproxen; Acetaminophen; Tramadol

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Dimethylamines; Methylamines; Lipids

Limitations and Caveats

Research study as described in the results manuscript only evaluated 30 subjects but it is the first of it's kind. Our analysis was not powered to comprehensively evaluate the clinical and demographic factors that influence the local and systemic inflammatory response to implant placement surgery or drug response. In addition, we excluded smokers and patients with diabetes, autoimmune diseases, or other comorbidities that might influence the inflammatory response to implant placement surgery.

Results Point of Contact

• Title: Elliot V Hersh DMD, MS, PhD. Professor of Oral Surgery and Pharmacology
• Organization: University of Pennsylvania School of Dental Medicine

evhersh@upenn.edu

215-898-9686

Study Officials

• Elliot V Hersh, DMD, MS, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Katherine N Theken, PharmD, PhD

  University of Pennsylvania School of Dental Medicine and Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Administration of naproxen or acetaminophen will be masked by over-encapsulation
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Model Details: Double blind, randomized, active-controlled, two arms

Study Record Dates

• First Submitted: December 31, 2020
• First Posted: January 5, 2021
• Study Start: February 7, 2021
• Primary Completion: August 28, 2022
• Study Completion: August 28, 2022
• Last Updated: May 16, 2024
• Results First Posted: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)