Efficacy of Chronoterapy in Oral Surgery (ECOS)

Efficacy of the Dosage of a Non-steroidal Anti-inflammatory (Ibuprofen) on Inflammation and Postoperative Pain After Lower Third Molar Surgery.

Lower third molar extraction is one of the most common treatments in oral surgery practice. It is a treatment with inherent complications such as postoperative pain, swelling or trismus. In order to minimize disconfort after extraction, analgesic and anti-inflammatory medication is prescribed. Recently, it is seen that circadian rhythm may play an important role on drugs metabolism, modulating its effect depending on the moment of administration. The aim of the study is to analyze if dosage modification of a Non Steroideal Anti-Inflammatory (ibuprofen) affects on postoperative pain, swelling and open mouth limitation comparing to the normal dosage.

Study Overview

• Status: Completed
• Conditions: Pain; Inflammatory Response; Trismus; Tooth, Impacted
• Intervention / Treatment: Drug: Ibuprofen 400 mg; Drug: Ibuprofen 400 mg

Detailed Description

A randomized crossover split-mouth clinical trial will be performed. After third molar extractions, patients will be prescribed ramdomly in one side wit the normal medication dosage while the contralateral side will be prescribed a modified dosage. Moreover, a blood sample will be obtained to analize the inflammatory profile.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28040
    • Fabian Perez Gonzalez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 18 and 35 years old
• Bilateral retained lower third molar

Exclusion Criteria:

• NSAID allergic
• Contraindication for surgical removal of third molar

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Modified dosage; Ibuprofen pill at morning and afternoon; Placebo at night	Drug: Ibuprofen 400 mg; morning and afternoon; Other Names: Modified dosage; Drug: Ibuprofen 400 mg; morning, afternoon and night; Other Names: Conventional dosage
Active Comparator: Normal dosage; Ibuprofen three times a day: morning, afternoon and night	Drug: Ibuprofen 400 mg; morning and afternoon; Other Names: Modified dosage; Drug: Ibuprofen 400 mg; morning, afternoon and night; Other Names: Conventional dosage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post operative Pain	Postoperative pain with visual analogue scale (VAS) from 0 (no pain) to 10 (maximum pain)	From the day of the surgical procedure to the seventh-day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Swelling	Distance from tragus to pogonion in milimiters	Baseline and post operatory (day 1, day 3, day 7)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trismus	Open mouth limitation in milimiters. Interincisal distance	Baseline and post operatory (day 1, day 3 and day 7)

Collaborators and Investigators

• Sponsor: Universidad Complutense de Madrid
• Collaborators: McGill University

Publications and helpful links

General Publications

• Gutierrez-Corrales A, Campano-Cuevas E, Castillo-Dali G, Serrera-Figallo MA, Torres-Lagares D, Gutierrez-Perez JL. Relationship between salivary biomarkers and postoperative swelling after the extraction of impacted lower third molars. Int J Oral Maxillofac Surg. 2017 Feb;46(2):243-249. doi: 10.1016/j.ijom.2016.10.005. Epub 2016 Nov 3.
• Albuquerque AFM, Fonteles CSR, do Val DR, Chaves HV, Bezerra MM, Pereira KMA, de Barros Silva PG, de Lima BB, Soares ECS, Ribeiro TR, Costa FWG. Effect of pre-emptive analgesia on clinical parameters and tissue levels of TNF-alpha and IL-1beta in third molar surgery: a triple-blind, randomized, placebo-controlled study. Int J Oral Maxillofac Surg. 2017 Dec;46(12):1615-1625. doi: 10.1016/j.ijom.2017.05.007. Epub 2017 Jun 10.
• Keller M, Mazuch J, Abraham U, Eom GD, Herzog ED, Volk HD, Kramer A, Maier B. A circadian clock in macrophages controls inflammatory immune responses. Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21407-12. doi: 10.1073/pnas.0906361106. Epub 2009 Dec 1.
• Curtis AM, Fagundes CT, Yang G, Palsson-McDermott EM, Wochal P, McGettrick AF, Foley NH, Early JO, Chen L, Zhang H, Xue C, Geiger SS, Hokamp K, Reilly MP, Coogan AN, Vigorito E, FitzGerald GA, O'Neill LA. Circadian control of innate immunity in macrophages by miR-155 targeting Bmal1. Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):7231-6. doi: 10.1073/pnas.1501327112. Epub 2015 May 20.

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2021
• Primary Completion (Actual): December 10, 2021
• Study Completion (Actual): February 2, 2022

Study Registration Dates

• First Submitted: October 14, 2021
• First Submitted That Met QC Criteria: November 16, 2021
• First Posted (Actual): November 18, 2021

Study Record Updates

• Last Update Posted (Actual): February 3, 2022
• Last Update Submitted That Met QC Criteria: February 2, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Randomized; Ibuprofen; Chronotherapy; Third molar
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Stomatognathic Diseases; Neuromuscular Manifestations; Tooth Diseases; Spasm; Tooth, Impacted; Trismus; 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; Ibuprofen
• Other Study ID Numbers: 2019-000736-25

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