Preemptive Analgesia With Celecoxib for Acute Dental Pain Management

• ClinicalTrials.gov Identifier: NCT04790812
• Recruitment Status: Recruiting
• First Posted: March 10, 2021
• Last Update Posted: October 5, 2021
• Sponsor: The University of Texas Health Science Center, Houston
• Information provided by (Responsible Party): Harry Gilbert, DDS, The University of Texas Health Science Center, Houston

Study Description

Brief Summary:

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. .

Condition or disease	Intervention/treatment	Phase
Pain, Postoperative	Drug: Celecoxib; Drug: Acetaminophen; Drug: Placebo	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A randomized, double-blind, placebo-controlled, prospective clinical trial. Subjects will be given a single oral dose of celecoxib 200 mg with placebo (Group 1), or celecoxib 200 mg in combination with acetaminophen 1000 mg (Group 2) 30 to 60 minutes prior to the dental procedure.
• Masking: Double (Participant, Care Provider)
• Masking Description: Patient regimen randomization will be achieved by use of a random number generator. The care provider or clinic faculty/nurse will blindly administer the regimen to the patient prior to procedure. A placebo capsule will be used to mimic the acetaminophen capsule to maintain blinding of care provider and patient. Preemptive medications will be dispensed in disposable containers prior to the start of daily operations. The research member tasked with dispensing will not be involved with the administration of medications to patients on the day of surgery. The PI and other members of the research team will not be blinded.
• Primary Purpose: Treatment
• Official Title: Single Dose Oral Celecoxib (With or Without Acetaminophen) for Acute Post-operative Pain Following Impacted Third Molar Surgery.
• Actual Study Start Date: April 22, 2021
• Estimated Primary Completion Date: April 22, 2023
• Estimated Study Completion Date: April 22, 2024

Arms and Interventions

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 Name: 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 Name: Tylenol, APAP

Outcome Measures

Primary Outcome Measures :

1. Pain as assessed by a Visual Analogue Scale (VAS) [ Time Frame: 3 hours after procedure ]
   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.
2. Pain as assessed by a Visual Analogue Scale (VAS) [ Time Frame: 8 hours after procedure ]
   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. Pain as assessed by a Visual Analogue Scale (VAS) [ Time Frame: 12 hours after procedure ]
   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.
4. Pain as assessed by a Visual Analogue Scale (VAS) [ Time Frame: 18 hours after procedure ]
   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.
5. Pain as assessed by a Visual Analogue Scale (VAS) [ Time Frame: 24 hours after procedure ]
   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.
6. Pain as assessed by a Visual Analogue Scale (VAS) [ Time Frame: 36 hours after procedure ]
   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.
7. Pain as assessed by a Visual Analogue Scale (VAS) [ Time Frame: 48 hours after procedure ]
   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. Pain as assessed by a Visual Analogue Scale (VAS) [ Time Frame: 72 hours after procedure ]
   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.

Secondary Outcome Measures :

1. Pain as assessed by a Categorical Descriptive Questionnaire [ Time Frame: 3 hours after procedure ]
   A questionnaire will ask whether the study participant's pain is dull, aching, throbbing, pulsing, stinging, and/or stabbing. Results will be reported categorically as the number of participants who experience the pain descriptor.
2. Pain as assessed by a Categorical Descriptive Questionnaire [ Time Frame: 8 hours after procedure ]
   A questionnaire will ask whether the study participant's pain is dull, aching, throbbing, pulsing, stinging, and/or stabbing. Results will be reported categorically as the number of participants who experience the pain descriptor.
3. Pain as assessed by a Categorical Descriptive Questionnaire [ Time Frame: 12 hours after procedure ]
   A questionnaire will ask whether the study participant's pain is dull, aching, throbbing, pulsing, stinging, and/or stabbing. Results will be reported categorically as the number of participants who experience the pain descriptor.
4. Pain as assessed by a Categorical Descriptive Questionnaire [ Time Frame: 18 hours after procedure ]
   A questionnaire will ask whether the study participant's pain is dull, aching, throbbing, pulsing, stinging, and/or stabbing. Results will be reported categorically as the number of participants who experience the pain descriptor.
5. Pain as assessed by a Categorical Descriptive Questionnaire [ Time Frame: 24 hours after procedure ]
   A questionnaire will ask whether the study participant's pain is dull, aching, throbbing, pulsing, stinging, and/or stabbing. Results will be reported categorically as the number of participants who experience the pain descriptor.
6. Pain as assessed by a Categorical Descriptive Questionnaire [ Time Frame: 36 hours after procedure ]
   A questionnaire will ask whether the study participant's pain is dull, aching, throbbing, pulsing, stinging, and/or stabbing. Results will be reported categorically as the number of participants who experience the pain descriptor.
7. Pain as assessed by a Categorical Descriptive Questionnaire [ Time Frame: 48 hours after procedure ]
   A questionnaire will ask whether the study participant's pain is dull, aching, throbbing, pulsing, stinging, and/or stabbing. Results will be reported categorically as the number of participants who experience the pain descriptor.
8. Pain as assessed by a Categorical Descriptive Questionnaire [ Time Frame: 72 hours after procedure ]
   A questionnaire will ask whether the study participant's pain is dull, aching, throbbing, pulsing, stinging, and/or stabbing. Results will be reported categorically as the number of participants who experience the pain descriptor.
9. Number of Participants who Receive an Emergency Analgesic Intervention [ Time Frame: Any time during the 72 hours after procedure ]
   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).

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Caroline K Cutbirth, BS; 713-486-4315; Caroline.K.Cutbirth@uth.tmc.edu

Contact: Harry D Gilbert, DDS; 713-486-4315; Harry.D.Gilbert@uth.tmc.edu

Locations

United States, Texas

University of Texas School of Dentistry; Recruiting

Houston, Texas, United States, 77054

Contact: Robert D Spears, PhD, MS 713-486-4013 Robert.D.Spears@uth.tmc.edu

Contact: Auco Dang, Director 713-486-4258 Auco.Dang@uth.tmc.edu

Principal Investigator: Harry D Gilbert, DDS

Sub-Investigator: Casandra L Barnes, BS

Sub-Investigator: Arthur H Jeske, DMD, PhD

Sub-Investigator: Alan L Myers, PharmD, PhD

Sub-Investigator: Kimberly S Ruona, DDS

Sponsors and Collaborators

The University of Texas Health Science Center, Houston

Investigators

• Principal Investigator: Harry D Gilbert, DDS; University of Texas School of Dentistry at Houston
• Study Director: Auco Dang; University of Texas School of Dentistry at Houston

More Information

Additional Information:

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. 

Publications:

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.

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.

Hawkey CJ. COX-1 and COX-2 inhibitors. Best Pract Res Clin Gastroenterol. 2001 Oct;15(5):801-20. Review.

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.

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. Review.

Nissen SE, Yeomans ND, Solomon DH, Lüscher 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.

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.

• Responsible Party: Harry Gilbert, DDS, DDS, Professor - Oral and Maxillofacial Surgery, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT04790812
• Other Study ID Numbers: HSC-DB-20-0118
• First Posted: March 10, 2021
• Last Update Posted: October 5, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pain; Neurologic Manifestations; Acetaminophen; Celecoxib; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action