Preemptive Analgesia With Celecoxib for Acute Dental Pain Management

Single Dose Oral Celecoxib (With or Without Acetaminophen) for Acute Post-operative Pain Following Impacted Third Molar Surgery.

The purpose of this study is to compare the effect on postoperative pain of a single agent nonsteroidal anti-inflammatory drug (NSAID) [celecoxib plus placebo] to an NSAID combination [celecoxib plus acetaminophen] administered preemptively to patients prior to impacted third molar surgery. .

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative
• Intervention / Treatment: Drug: Celecoxib; Drug: Placebo; Drug: Acetaminophen

Detailed Description

This randomized, double-blind, placebo-controlled, prospective clinical trial is designed to compare the postoperative pain reduction of a single agent nonsteroidal anti-inflammatory drug (NSAID) and NSAID combination regimen administered preemptively. Subjects will be given a single oral dose of a cyclooxygenase-2 (COX-2) selective inhibitor (celecoxib 200mg), or celecoxib 200 mg in combination with acetaminophen (APAP 1000 mg) 30 to 60 minutes prior to the procedure. Oral surgery involving at least one impacted mandibular third molar will be performed using a combination of intravenous sedation and local anesthesia following UTHealth School of Dentistry (UTSD) surgical protocol. All subjects will be released with identical postoperative instructions and prescriptions for pain management. Nonopioid pain management will be prescribed as follows: 600mg ibuprofen with 500 mg APAP every 6 hours for the first 3 days, then as needed for pain. Subjects will be asked to document medication consumption, postoperative pain and complications for the following 3 days using a Qualtrics survey. An oral and maxillofacial surgery resident or faculty on call can offer emergency intervention with prescription of an opioid analgesic.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Harry K Gilbert, DDS; Phone Number: 713-486-4315; Email: Harry.D.Gilbert@uth.tmc.edu
• Study Contact Backup: Name: Caroline D Cutbirth, BS; Phone Number: 713-486-4315; Email: Caroline.K.Cutbirth@uth.tmc.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) physical status classification 1 or 2
• at least 1 impacted mandibular third molar planned for extraction

Exclusion Criteria:

• ASA 3 or higher for physical status classification
• severe pericoronitis associated with third molar to be extracted
• any known allergies to NSAIDs, aspirin, acetaminophen, sulfa drugs
• history of cardiovascular or cerebrovascular disease
• hepatic disease or impairment
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Celecoxib plus Placebo; Single oral dose of celecoxib 200 mg with placebo 30 to 60 minutes prior to the dental procedure	Drug: Celecoxib; Single, preemptive oral dose 200mg of celecoxib. A cyclooxygenase-2 (COX-2) selective inhibitor for pain management. A COX-2 selective nonsteroidal anti-inflammatory drug (NSAID).; Other Names: Celebrex; COX-2 selective inhibitor, COX-2 selective NSAID; Drug: Placebo; A capsule with no active ingredients designed to mimic the appearance of the acetaminophen capsule to ensure blinding of patients and care providers.; Other Names: Inactive substance, inert substance
Active Comparator: Celecoxib plus Acetaminophen; Single oral dose of celecoxib 200 mg in combination with acetaminophen 1000 mg 30 to 60 minutes prior to the dental procedure.	Drug: Celecoxib; Single, preemptive oral dose 200mg of celecoxib. A cyclooxygenase-2 (COX-2) selective inhibitor for pain management. A COX-2 selective nonsteroidal anti-inflammatory drug (NSAID).; Other Names: Celebrex; COX-2 selective inhibitor, COX-2 selective NSAID; Drug: Acetaminophen; Single, preemptive oral dose 1000mg of acetaminophen. An over-the-counter medication for pain management.; Other Names: Tylenol, APAP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain as Assessed by a Visual Analogue Scale (VAS)	Psychometric response scale to be included in a questionnaire to evaluate pain intensity. A 0-10 pain scale will be used with visual "Faces" to correspond with the numerical values, with 10 indicating worse pain.	3 hours after procedure
Pain as Assessed by a Visual Analogue Scale (VAS)	Psychometric response scale to be included in a questionnaire to evaluate pain intensity. A 0-10 pain scale will be used with visual "Faces" to correspond with the numerical values, with 10 indicating worse pain.	8 hours after procedure
Pain as Assessed by a Visual Analogue Scale (VAS)	Psychometric response scale to be included in a questionnaire to evaluate pain intensity. A 0-10 pain scale will be used with visual "Faces" to correspond with the numerical values, with 10 indicating worse pain.	12 hours after procedure
Pain as Assessed by a Visual Analogue Scale (VAS)	Psychometric response scale to be included in a questionnaire to evaluate pain intensity. A 0-10 pain scale will be used with visual "Faces" to correspond with the numerical values, with 10 indicating worse pain.	18 hours after procedure
Pain as Assessed by a Visual Analogue Scale (VAS)	Psychometric response scale to be included in a questionnaire to evaluate pain intensity. A 0-10 pain scale will be used with visual "Faces" to correspond with the numerical values, with 10 indicating worse pain.	24 hours after procedure
Pain as Assessed by a Visual Analogue Scale (VAS)	Psychometric response scale to be included in a questionnaire to evaluate pain intensity. A 0-10 pain scale will be used with visual "Faces" to correspond with the numerical values, with 10 indicating worse pain.	36 hours after procedure
Pain as Assessed by a Visual Analogue Scale (VAS)	Psychometric response scale to be included in a questionnaire to evaluate pain intensity. A 0-10 pain scale will be used with visual "Faces" to correspond with the numerical values, with 10 indicating worse pain.	48 hours after procedure
Pain as Assessed by a Visual Analogue Scale (VAS)	Psychometric response scale to be included in a questionnaire to evaluate pain intensity. A 0-10 pain scale will be used with visual "Faces" to correspond with the numerical values, with 10 indicating worse pain.	72 hours after procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain as Assessed by a Categorical Descriptive Questionnaire	A questionnaire will ask whether the study participant's pain is dull, aching, throbbing, pulsing, stinging, stabbing, none and/or other. Results will be reported categorically as the number of participants who experience the pain descriptor.	3 hours after procedure
Pain as Assessed by a Categorical Descriptive Questionnaire	A questionnaire will ask whether the study participant's pain is dull, aching, throbbing, pulsing, stinging, stabbing, none and/or other. Results will be reported categorically as the number of participants who experience the pain descriptor.	8 hours after procedure
Pain as Assessed by a Categorical Descriptive Questionnaire	A questionnaire will ask whether the study participant's pain is dull, aching, throbbing, pulsing, stinging, stabbing, none and/or other. Results will be reported categorically as the number of participants who experience the pain descriptor.	12 hours after procedure
Pain as Assessed by a Categorical Descriptive Questionnaire	A questionnaire will ask whether the study participant's pain is dull, aching, throbbing, pulsing, stinging, stabbing, none and/or other. Results will be reported categorically as the number of participants who experience the pain descriptor.	18 hours after procedure
Pain as Assessed by a Categorical Descriptive Questionnaire	A questionnaire will ask whether the study participant's pain is dull, aching, throbbing, pulsing, stinging, stabbing, none and/or other. Results will be reported categorically as the number of participants who experience the pain descriptor.	24 hours after procedure
Pain as Assessed by a Categorical Descriptive Questionnaire	A questionnaire will ask whether the study participant's pain is dull, aching, throbbing, pulsing, stinging, stabbing, none and/or other. Results will be reported categorically as the number of participants who experience the pain descriptor.	36 hours after procedure
Pain as Assessed by a Categorical Descriptive Questionnaire	A questionnaire will ask whether the study participant's pain is dull, aching, throbbing, pulsing, stinging, stabbing, none and/or other. Results will be reported categorically as the number of participants who experience the pain descriptor.	48 hours after procedure
Pain as Assessed by a Categorical Descriptive Questionnaire	A questionnaire will ask whether the study participant's pain is dull, aching, throbbing, pulsing, stinging, stabbing, none and/or other. Results will be reported categorically as the number of participants who experience the pain descriptor.	72 hours after procedure
Number of Participants Who Receive an Emergency Analgesic Intervention	Emergency interventions are medications or treatments for postoperative pain not prescribed in study, including medications taken other than those prescribed for after the surgery, calling for prescription of medications other than those prescribed for after the surgery, and seeking outside dental/medical attention (for example: private practice or hospital).	Any time during the 72 hours after procedure

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: Harry D Gilbert, DDS, University of Texas School of Dentistry at Houston

Publications and helpful links

General Publications

• Ong CK, Lirk P, Seymour RA, Jenkins BJ. The efficacy of preemptive analgesia for acute postoperative pain management: a meta-analysis. Anesth Analg. 2005 Mar;100(3):757-773. doi: 10.1213/01.ANE.0000144428.98767.0E.
• Hawkey CJ. COX-1 and COX-2 inhibitors. Best Pract Res Clin Gastroenterol. 2001 Oct;15(5):801-20. doi: 10.1053/bega.2001.0236.
• Nissen SE, Yeomans ND, Solomon DH, Luscher TF, Libby P, Husni ME, Graham DY, Borer JS, Wisniewski LM, Wolski KE, Wang Q, Menon V, Ruschitzka F, Gaffney M, Beckerman B, Berger MF, Bao W, Lincoff AM; PRECISION Trial Investigators. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. N Engl J Med. 2016 Dec 29;375(26):2519-29. doi: 10.1056/NEJMoa1611593. Epub 2016 Nov 13.
• Gong L, Thorn CF, Bertagnolli MM, Grosser T, Altman RB, Klein TE. Celecoxib pathways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics. 2012 Apr;22(4):310-8. doi: 10.1097/FPC.0b013e32834f94cb. No abstract available.
• Bauer HC, Duarte FL, Horliana AC, Tortamano IP, Perez FE, Simone JL, Jorge WA. Assessment of preemptive analgesia with ibuprofen coadministered or not with dexamethasone in third molar surgery: a randomized double-blind controlled clinical trial. Oral Maxillofac Surg. 2013 Sep;17(3):165-71. doi: 10.1007/s10006-012-0360-7. Epub 2012 Sep 5.
• Cicconetti A, Bartoli A, Ripari F, Ripari A. COX-2 selective inhibitors: a literature review of analgesic efficacy and safety in oral-maxillofacial surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004 Feb;97(2):139-46. doi: 10.1016/j.tripleo.2003.08.032.
• Jung YS, Kim MK, Um YJ, Park HS, Lee EW, Kang JW. The effects on postoperative oral surgery pain by varying NSAID administration times: comparison on effect of preemptive analgesia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005 Nov;100(5):559-63. doi: 10.1016/j.tripleo.2005.02.065.
• May N, Epstein J, Osborne B. Selective COX-2 inhibitors: a review of their therapeutic potential and safety in dentistry. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001 Oct;92(4):399-405. doi: 10.1067/moe.2001.115127.

Helpful Links

• Background information reference to The Centers for Disease Control and Prevention (CDC) on statistics relevant to the opioid epidemic supporting the need for other pain modalities.

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2021
• Primary Completion (Actual): March 1, 2023
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: November 5, 2020
• First Submitted That Met QC Criteria: March 5, 2021
• First Posted (Actual): March 10, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Cyclooxygenase 2 Inhibitors; Celecoxib; Acetaminophen
• Other Study ID Numbers: HSC-DB-20-0118

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No