Controlled Trial to Determine Most Effective Post-Operative Analgesia After Third Molar Extraction

"A Prospective Randomized Controlled Trial to Determine Most Effective Post-Operative Analgesia After Third Molar Extraction"

This is a prospective randomized clinical trial that will investigate which post-operative medications in conjunction with a multimodal analgesia approach can most effectively control post-operative pain and reduce opioid consumption.

Study Overview

• Status: Completed
• Conditions: Pain, Acute; Third Molar; Oral Surgery; Pain, Post-operative
• Intervention / Treatment: Drug: Acetaminophen; Drug: Ibuprofen; Drug: Hydrocodone; Drug: Ketorolac; Drug: Oxycodone

Detailed Description

The recruitment of patients is covered in another section. Once patients are recruited based on inclusion/exclusion criteria, they will be consented and randomized into one of the 2 arms. The pre and perioperative anesthesia protocols will be identical for each arm and will consist of an opioid free general anesthesia. Local anesthesia will be given in an identical fashion in all arms. One cartridge of 2% lidocaine with 1:100k epinephrine will be given as a nerve block for the inferior alveolar nerve bilaterally. Then one cartridge of 0.5% bupivacaine with 1:200k epinephrine will be locally injected for at each of the four 3rd molar sites. Both arms will be injected with 133mg (10cc) of liposomal bupivacaine. The third molars will then be extracted in typical fashion. Each patient will be attached to one of two postoperative arms distinguished by the post-operative medications received. The control arm will be 650 mg Tylenol PO scheduled q6h, 600mg Motrin per os (PO) scheduled q6h and 5 mg hydrocodone PO pro re nata (PRN) q6h. The study arm will be 10 mg Toradol PO q6h, 650 mg acetaminophen PO scheduled q6h, and 5 mg oxycodone PO PRN q6h. The blinded medication will be either the 600mg Motrin or the 10mg Toradol. The patients will be standard 3rd molar extraction post-operative instructions as well as specific instructions on how to take medications. The identity of the patients will be linked to a key that will be kept in a locked box inside a keypad entry office. All future pain assessors will be blinded to the arm of the study in which the patient is attached. The patients will respond to daily pain intensity scores, medications taken, quality of life measures through a survey. The patients will be taught about the surveys during the consent process and again postoperatively. An email or phone will be done for the patients on the following morning for the first 5 days postoperatively. The patient will be instructed to complete the survey that will assess pain, medications taken and quality of life items. The patients will submit these daily until they return to clinic 5 days post-op where they will again submit one survey collectively discussing the outcomes of the previous 5 days. All arms will have the primary investigator's cell phone number if any adverse reactions present themselves.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92134
      • Naval Medical Center San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female 18 years or older
• Scheduled for 3rd molar extraction (x4) with at least one mandibular 3rd molar impacted
• American Society of Anesthesiologists classification 1 or 2
• Able to provide consent, adhere to study schedule, complete study journal, and understand English

Exclusion Criteria:

• History of hypersensitivity or idiosyncratic reaction to amide-type local anesthetics or opioids
• Contraindication to lidocaine, epinephrine, bupivacaine, or hydrocodone
• Significant drug allergy history
• Currently pregnant or nursing at time of study or within 1 month of drug administration
• Severe renal or hepatic impairment, significant cardiovascular disease; migraines, frequent headaches.
• Use of any of the following medication within 1 month of EXPAREL infiltration or if the medications are being given to control pain: Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin Nonadrenaline Reuptake Inhibitors (SNRIs), gabapentin, pregabalin, or duloxetine.
• Current use of systemic glucocorticosteroids within 1 month of enrollment in the study
• No concurrent surgical procedures within 2 weeks before or after 3rd molar extractions

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Acetaminophen, Ibuprofen, Hydrocodone Control arm; The control arm will be 650 mg Acetaminophen PO scheduled q6h, 600mg Ibuprofen PO scheduled q6h and 5 mg Hydrocodone PO PRN q6h.	Drug: Acetaminophen; 650 mg q 6h scheduled; Other Names: Tylenol; Drug: Ibuprofen; 600 mg PO scheduled q6h; Other Names: Motrin; Drug: Hydrocodone; 5 mg hydrocodone PO PRN q6h; Other Names: Vicodin
Experimental: Ketorolac, Acetaminophen, Oxycodone Study arm; The study arm will be 10 mg Ketorolac PO q6h, 650 mg Acetaminophen PO scheduled q6h, and 5 mg Oxycodone PO PRN q6h.	Drug: Acetaminophen; 650 mg q 6h scheduled; Other Names: Tylenol; Drug: Ketorolac; 10 mg PO q 6h scheduled; Other Names: Toradol; Drug: Oxycodone; 5 mg PO PRN; Other Names: Oxycontin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post operative pain control after third molar extraction	All participants will complete a daily survey on the medications taken to relieve pain.	Up to five days post operative procedure.
Post operative opioid use after third molar extraction	Daily survey will be used to assess the amount of post operative opioid us including dosage and frequency of use.	Up to five days post operative procedure.
Post operative pain assessment after third molar extraction	Participants fill out daily for five days post operative procedure the Numeric Pain Rating Scale (NPRS). This is a ten point scale with 0 = No pain, 5 = Moderate pain, 10 = Worst possible pain. The higher the number is a worse outcome.	Up to five days post operative procedure.
Post operative quality of life assessment after third molar extraction	Post operative quality of life was ascertained with the 10 point Likert scaled question, "What is your rating for your actual overall comfort?'. 1 = Very low overall comfort, 5 = Neither low or high overall comfort, 10 = Very high overall comfort. The higher the score means a better outcome. This question is part of the daily survey that participants filled out for five days post operative procedure.	Up to five days after third molar extraction.

Collaborators and Investigators

• Sponsor: United States Naval Medical Center, San Diego
• Investigators: Principal Investigator: Patrick T Morrell, DMD, United States Naval Medical Center, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2018
• Primary Completion (Actual): November 3, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: June 4, 2024
• First Submitted That Met QC Criteria: June 25, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): July 10, 2024
• Last Update Submitted That Met QC Criteria: July 8, 2024
• Last Verified: July 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; Central Nervous System Depressants; 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; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Ketorolac; Acetaminophen; Ibuprofen; Oxycodone; Hydrocodone
• Other Study ID Numbers: NMCSD.2018.0014

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