Comparison of the Clinical Efficacy of Ketoprofen, Associated or Not With Omeprazole in Lower Third Molar Removal

Study Overview
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Brief Summary
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The control of pain, swelling and trismus in patients undergoing oral and maxillofacial surgery is frequently performed through the administration of non-steroidal anti-inflammatory drugs (NSAIDS). The present study aims to evaluate in a double blind, randomized and crossover manner the clinical efficacy of ketoprofen (immediate release - 100 mg) and ketoprofen in association with omeprazole (modified release - 200 mg ketoprofen with 20 mg omeprazole) in 50 patients aged 18 years or older that require removal of both lower third molars symmetrically positioned. After collection, data will be analyzed by means of graphs and tables to allow the appropriate analyses. Paired t-test will be used to compare the duration of surgeries. Nonparametric Wilcoxon test will be used for the analysis of rescue medication and postoperative pain parameters (visual analog scale). Data of mouth opening and swelling will be statistically analyzed through analysis of variance (ANOVA) followed by Tukey's test for multiple comparisons. Statistical significance will be set at 5%. Results will be presented as mean ± standard deviation of the mean.

Detailed Description
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Studies have shown that NSAIDS exert their therapeutic effect by the inhibition of cyclooxigenases (COX) 1 and 2, which determines the inhibition of prostaglandins production whose effects potentiate the action of many inflammatory mediators. The protocol for the administration of these formulations will involve the administration of a tablet of the immediate release product (100 mg) every 12 hours, and one capsule of the modified release product (200 mg ketoprofen with omeprazole) every 24 hours, during 4 days. The following parameters will be analyzed: subjective postoperative pain evaluation, with the aid of a visual analogue scale, mouth opening before the surgery, on the 2nd and 7th postoperative days (moment of suture removal), beginning and duration of the surgery after anesthetic administration, incidence, type and severity of adverse reactions, total amount of rescue analgesic medication (paracetamol), facial swelling measured on the 2nd and 7th postoperative days (in comparison with the measurements before the surgery).

Official Title
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Comparison of the Clinical Efficacy of Ketoprofen, Associated or Not With Omeprazole, in the Control of Pain, Swelling and Trismus in Lower Third Molar Removal

Conditions
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Pain, Other Surgical Procedures

Intervention / Treatment
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* Drug: Ketoprofen
* Drug: Ketoprofen and Omeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Need of lower third molar surgeries in similar positions Exclusion Criteria: Presence of systemic diseases; Presence of local inflammation and/or infection; Any history of allergic reaction to local anesthetics, gastrointestinal bleeding or ulceration; Cardiovascular, kidney or hepatic diseases; Patients who are making use of antidepressants, diuretics or anticoagulants; Asthma and allergy to aspirin, naproxen or any other nonsteroidal antiinflammatory drug; Regular use of any nonsteroidal antiinflammatory drug, pregnancy or breast feeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surgery with Ketoprofen<br>Fifty healthy volunteers underwent removal one of lower third molar, will be treated to control pain, swelling and trismus with ketoprofen 100 mg | Drug: Ketoprofen<br>* Clinical efficacy of the Ketoprofen 100 mg was study after lower third molar surgery.<br>* Other names: Lower third molar surgery with Ketoprofen;|
| Experimental: Surgery with Ketoprofen and Omeprazole<br>Fifty healthy volunteers underwent removal the other lower third molars, will be treated to control pain, swelling and trismus with ketoprofen 200 mg associated with Omeprazole 20 mg | Drug: Ketoprofen and Omeprazole<br>* Clinical efficacy of the Ketoprofen 200 mg and Omeprazole 20 mg will be study after lower third molar surgery.<br>* Other names: Lower third molar surgery with Ketoprofen and Omeprazole;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective evaluation of postsurgical pain | Subjective evaluation of postsurgical pain, which was annotated by the volunteer, a Visual Analogue Scale (VAS, 0-100 mm) at the fourth postoperative hour. | Fourth postoperative hour | 
| Quality of anesthesia during surgery based on a category 3point scale | Quality of anesthesia during surgery based on a category 3point scale: 1) the patient reported no discomfort; 2) the patient reported discomfort, without the need to supplement the anesthesia; 3) reported some discomfort by the patient, requiring anesthesia complementation. Intraoral bleeding that will be evaluated by the surgeon according to a 3point scale (1: minimal, 2: normal and 3: Maximum), immediately after the following steps: injection of the first cartridge anesthesia, incision, mucoperiosteal detachment, osteotomies, tooth section, extraction, cleaning and suturing. | During the surgical procedure | 
| Intraoperative bleeding, rated by the surgeon according to a 3 point category rating scale | Intraoperative bleeding, rated by the surgeon according to a 3 point category rating scale (1 minimal bleeding; 2 normal bleeding; 3 excessive bleeding) (SISK, 1986), immediately after the following steps: injection of the first cartridge of articaine, tissue incision, flap reflection, bone removal (when this procedure was necessary), tooth extraction, cleaning of the operated site, and completion of suturing. | During the surgical procedure | 
| Heart rate | Median heart rate to be verified and recorded surgical at moments described above, carried out with the aid of a system for monitoring hemodynamic parameters | During the surgical procedure | 
| Oxygen saturation | Median oxygen saturation recorded at surgical moments described above, carried out with the aid of a system for monitoring hemodynamic parameters. | During the surgical procedure | 
| Systolic blood pressure | Median systolic blood pressure to be verified and recorded at surgical moments previously described (injection of the first cartridge anesthesia, incision, mucoperiosteal detachment, osteotomies, tooth section, extraction, cleaning and suturing), carried out with the aid of a system for monitoring hemodynamic parameters | During the surgical procedure | 
| Diastolic blood pressure | Median diastolic blood pressure to be verified and recorded at surgical moments previously described (injection of the first cartridge anesthesia, incision, mucoperiosteal detachment, osteotomies, tooth section, extraction, cleaning and suturing), carried out with the aid of a system for monitoring hemodynamic parameters | During the surgical procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mouth opening (mm) between the mesial-incisal corners of the upper and lower right central incisors at maximum opening of the jaws | Mouth opening (mm) between the mesial-incisal corners of the upper and lower right central incisors at maximum opening of the jaws was measured and recorded before the surgery and during the second and seventh postoperative days. | Second and Seventh postoperative days | 
| Onset and duration of surgery after administration of anesthetic | Will only be considered those surgeries in which there is no long time gap between the two surgical times. | During the surgery | 
| Incidence, type and severity of adverse reactions | Will be considered as adverse reactions: gastrointestinal irritation, nausea, vomiting, bleeding, allergy, headache, dizziness, drowsiness or any other type of reaction presented after surgery. | Seventh postoperative day | 
| Total amount of rescue medication | The total amount of rescue medication that was used by the patient during the postoperative period (paracetamol 750 mg) will be analyzed | Seventh postoperative day | 
| Measurement the facial edema distance between the lateral corner of the eye and the gonion, away from the tragus corner of the mouth and away from the tragus to the soft tissue of pogonion. | It will apply the method used by Ustun et al. (2003), which takes into account the sum of the following measures (obtained with flexible tape measure): A) distance between the lateral corner of the eye and the gonion, B) away from the tragus corner of the mouth and C) away from the tragus to the soft tissue of pogonion. Preoperative sum of three measures will be considered as the baseline that way. The difference between the values obtained in the postoperative period and baseline indicate the facial edema in the 2nd and 7th days. | On the second day after surgery and on the seventh day after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketofrofen, Omeprazole, Lower Third Molar, Oral Surgery