Effect of Photobiomodulation to Reduce Post-operative Pain After Endodontic Surgery

Study Overview
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Brief Summary
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The objective of this study will be to evaluate if photobiomodulation (FBM) can reduce postoperative pain in patients who will undergo endodontic surgery. For this randomized, controlled and double-blind clinical study, 34 patients without comorbidities who need endodontic surgery in the upper jaw (15 to 25 teeth) will be recruited. They will be randomly divided into an experimental group (n = 17) photobiomodulation (808nm, 100 mW, and 4J/cm2 with 5 points per vestibular). Applications will be made in the immediate postoperative period and 24 hours after surgery. Control group (n = 17) a FBM simulation will be performed in the same way as in the experimental group. In this group, the required analgesia will be administered within the standard with ibuprofen. Both groups will perform the necessary conventional procedures considered the gold standard in the literature. Both the patient and the evaluator will be blinded to the intervention performed. The primary outcome variable of the study will be postoperative pain, which will be assessed using the visual analog scale at all postoperative control visits (baseline, 24 hours and 7 days). As for the secondary outcome variables, the amount of systemic medication received according to the patient's need (will be provided by the investigator).. Radiographic images will be obtained after 1 and 2 months for evaluation of the repair (dimensions of the lesion, radiopacity). These radiographs will be taken digitally with the positioners implemented. Edema, ecchymosis, and evaluation of soft tissues in the anterior portion of the intra and extra-oral maxilla will also be evaluated. In addition, a digital thermometer. These parameters will be evaluated 24 hours and 7 days after the intervention. The X-rays will be taken in the 1st and 3rd month respectively.

Detailed Description
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Photobiomodulation (FBM) has shown favorable results in the postoperative period of endodontic surgery, however, up to now, the level of evidence in this procedure is low. The objective of this study will be to evaluate if photobiomodulation (FBM) can reduce postoperative pain in patients who will undergo endodontic surgery. For this randomized, controlled, and double-blind clinical study, 34 Uruguayan participants of both sexes who previously consulted at the Clínica Universitaria de la Salud, with a diagnosis of periodontitis with an apical lesion less than 10mm with or without a fistula, diagnosed clinically and radiographically, in the upper maxillary region (from 15 to 25) will be recruited. Participants included in the study must have periapical lesions who have already undergone endodontic treatment (lesions smaller than 10mm in their greatest diameter - Metin et al., 2018, single and chronic lesions), no comorbidities, age from 18 to 70 years, both genders, healthy permanent teeth with good hygiene. Participants will be excluded if they are taking drugs that affect bone metabolism and the inflammatory process (for example corticosteroids, bisphosphonates), Smokers, pregnant or lactating women, if used anti-inflammatory drugs in the last 3 months before surgery, who do not follow the guidelines or have an injury in the acute phase (pain, edema, exudate). They will be randomly divided into an experimental group (n = 17) photobiomodulation (808nm, 100 mW, and 4J/cm2 with 5 points per vestibular). Applications will be made in the immediate postoperative period and 24 hours after surgery. Control group (n = 17) FBM simulation will be performed in the same way as in the experimental group. In this group, the required analgesia will be administered within the standard with ibuprofen. Both groups will perform the necessary conventional procedures considered the gold standard in the literature. Both the patient and the evaluator will be blinded to the intervention performed. The primary outcome variable of the study will be postoperative pain, which will be assessed using the visual analog scale at all postoperative control visits (baseline, 24 hours, and 7 days). As for the secondary outcome variables, the amount of systemic medication received according to the patient's need (will be provided by the investigator). Radiographic images will be obtained after 1 and 3 months for evaluation of the repair (dimensions of the lesion, radiopacity). These radiographs will be taken digitally with the positioners implemented. Edema, ecchymosis, and evaluation of soft tissues in the anterior portion of the intra and extra-oral maxilla will also be evaluated. In addition, the temperature with a digital thermometer. These parameters will be evaluated 24 hours and 7 days after the intervention. The X-rays will be taken in the 1st and 3rd months, respectively. Once all the data have been collected, their normality will be tested, and the one-way ANOVA test and the complementary Tukey test will be carried out. Data will be presented as mean ± standard deviation (SD) and the accepted p-value will be <0.0

Official Title
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Effect of Photobiomodulation to Reduce Post-operative Pain After Endodontic Surgery: a Randomized Controlled Clinical Trial

Conditions
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Photobiomodulation, Endodontic Disease, Pain, Inflammation, Surgery

Intervention / Treatment
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* Drug: Ibuprofen
* Other: Photobiomodulation simulation
* Device: Photobiomodulation
* Other: Ibuprofen simulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria :• Patients with periapical lesions who have already undergone endodontic treatment (lesions smaller than 10mm in their greatest diameter - Metin et al., 2018, single and chronic lesions) Patients with not comorbidities, Age from 18 to 70 years, Both genders, Healthy permanent teeth with good hygiene. Exclusion Criteria: Who are taking drugs that affect bone metabolism and the inflammatory process (for example: corticosteroids, bisphosphonates), Smokers, pregnant or lactating women, Who used anti-inflammatory drugs in the last 3 months before surgery. Who for any reason interrupted the evolution of the treatment for not attending joint appointments. Patients who do not follow the guidelines or have an injury in the acute phase (pain, edema, exudate)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This randomized, controlled, double-blind superiority clinical trial meets the criteria for designing a clinical trial in accordance with the SPIRIT Statement. It was accepted by Research Ethics Committee (CEP) of the Catholic University of Uruguay
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: G1- Control group<br>Conventional treatment + FBM simulation (n = 17 patients): All participants will undergo the same conventional surgical procedure. Patients will receive the FBM simulation and will be treated identically to the G2 group. The person responsible for applying the FBM will simulate the radiation by placing the devices in the same places described for the FBM group, however, the equipment will remain turned off. Thus for the participant does not identify the group to which he belongs, the device activation sound (beep) will be recorded and it will turn on at the time of application. | Drug: Ibuprofen<br>* All participants will undergo the same conventional surgical procedure. Patients will receive the FBM simulation and will be treated identically to the G2 group.<br>* Other names: antinflamatory;Other: Photobiomodulation simulation<br>* The person responsible for applying the FBM will simulate the radiation by placing the devices in the same places described for the FBM group, however, the equipment will remain turned off.<br>|
| Experimental: G2- Intervention group<br>Conventional treatment with placebo ibuprofen + FBM (n = 17) All participants will undergo the same surgical procedure. Patients will receive FBM (Table 1) and will be treated identically to the G2 group. The irradiated region will be on the lesion at 4 equidistant points on the vertex of a flat square 1 cm away. A dot will be irradiated in the middle of the square (Figure 1). Placebo ibuprofen will be manipulated. | Device: Photobiomodulation<br>* . Patients will receive FBM and will be treated identically to the G2 group. The irradiated region will be on the lesion at 4 equidistant points on the vertex of a flat square 1 cm away.<br>Other: Ibuprofen simulation<br>* Placebo ibuprofen will be manipulated by pharmacy (Matias Gonzalez)<br>* Other names: antinflamatory placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain in postoperative period - baseline | Pain will be measured during the immediate postoperative period of endodontic surgery using the Visual Analogue Scale (VAS) measured in millimeters, where 0 is no pain and 10 is the worst pain in life (Metin et al. ., 2018, Sampaio-Filho et al., 2018). | at baseline | 
| Pain in postoperative period - 24 hours after treatment | Pain will be measured at 24hours of postoperative period of endodontic surgery using the Visual Analogue Scale (VAS) measured in millimeters, where 0 is no pain and 10 is the worst pain in life (Metin et al. ., 2018, Sampaio-Filho et al., 2018). | 24 hours after treatment | 
| Pain in postoperative period -7 days after treatment | Pain will be measured at 7d of postoperative period of endodontic surgery using the Visual Analogue Scale (VAS) measured in millimeters, where 0 is no pain and 10 is the worst pain in life (Metin et al., 2018, Sampaio-Filho et al., 2018). | 7 days after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantity of painkillers ingested in the period - baseline | the number of painkillers ingested will be counted. The analgesic used will be only paracetamol that will be administered to the patient, but it is advisable to take it only in case of pain (Sampaio-Filho et al., 2018). A procedure will be carried out to monitor the adherence of the participants (for example, each patient will be asked to bring the pain reliever pack to the appointment to see how it is used). | at baseline | 
| Quantity of painkillers ingested in the period - 24 hours after treatment | the quantity of painkillers ingested in the 24-hours will be counted. The analgesic used will be only paracetamol that will be administered to the patient, but it is advisable to take it only in case of pain (Sampaio-Filho et al., 2018). A procedure will be carried out to monitor the adherence of the participants (for example, each patient will be asked to bring the pain reliever pack to the appointment to see how it is used). | 24 hours after treatment | 
| Quantity of painkillers ingested in the period - 7 days after treatment | the number of painkillers ingested in the 7-day period will be counted. The analgesic used will be only paracetamol that will be administered to the patient, but it is advisable to take it only in case of pain (Sampaio-Filho et al., 2018). A procedure will be carried out to monitor the adherence of the participants (for example, each patient will be asked to bring the pain reliever pack to the appointment to see how it is used). | 7 days after treatment | 
| Edema - baseline | A scale will be used to quantify the amount of edema as recommended by some authors (Metin et al., 2018). The scale is made up of scores from 0 to 3, where: 0 = no edema, 1 = intraoral edema, 2 = extraoral edema, 3 = diffuse edema (Metin et al., 2018). | at baseline | 
| Edema - 24 hours after treatment | A scale will be used to quantify the amount of edema as recommended by some authors (Metin et al., 2018). The scale is made up of scores from 0 to 3, where: 0 = no edema, 1 = intraoral edema, 2 = extraoral edema, 3 = diffuse edema (Metin et al., 2018). | 24 hours after treatment | 
| Edema - 7 days after treatment | A scale will be used to quantify the amount of edema as recommended by some authors (Metin et al., 2018). The scale is made up of scores from 0 to 3, where: 0 = no edema, 1 = intraoral edema, 2 = extraoral edema, 3 = diffuse edema (Metin et al., 2018). | 7 days after treatment | 
| Ecchymosis - baseline | is bleeding in the subcutaneous tissue, with a diameter greater than 1 cm, which is caused by the rupture of one or more blood capillaries and one of the causes is surgical trauma. Ecchymosis: 0 = no color change, 1 = spot smaller than 4 cm in diameter, 2 = spot 4-10 cm in diameter, 3 = spot larger than 10 cm in diameter (Metin et al., 2018). | at baseline | 
| Ecchymosis - 24 hours after treatment | is bleeding in the subcutaneous tissue, with a diameter greater than 1 cm, which is caused by the rupture of one or more blood capillaries and one of the causes is surgical trauma. Ecchymosis: 0 = no color change, 1 = spot smaller than 4 cm in diameter, 2 = spot 4-10 cm in diameter, 3 = spot larger than 10 cm in diameter (Metin et al., 2018). | 24 hours after treatment | 
| Ecchymosis -7 days after treatment | is bleeding in the subcutaneous tissue, with a diameter greater than 1 cm, which is caused by the rupture of one or more blood capillaries and one of the causes is surgical trauma. Ecchymosis: 0 = no color change, 1 = spot smaller than 4 cm in diameter, 2 = spot 4-10 cm in diameter, 3 = spot larger than 10 cm in diameter (Metin et al., 2018). | 7 days after treatment | 
| Soft tissue healing - baseline | Score 1: no opening at the incision line, no drainage (pus or exudate), no inflammation, no pain. Score 2: no opening at the incision line, no drainage, mild swelling, mild pain. Score 3: no opening at the incision line, active drainage, advanced inflammation, moderate to advanced pain. Score 4: opening at the incision line, active drainage, advanced inflammation, ongoing pain. | at baseline | 
| Soft tissue healing - 24 hours after treatment | Score 1: no opening at the incision line, no drainage (pus or exudate), no inflammation, no pain. Score 2: no opening at the incision line, no drainage, mild swelling, mild pain. Score 3: no opening at the incision line, active drainage, advanced inflammation, moderate to advanced pain. Score 4: opening at the incision line, active drainage, advanced inflammation, ongoing pain. | 24 hours after treatment | 
| Soft tissue healing -7 days after treatment | Score 1: no opening at the incision line, no drainage (pus or exudate), no inflammation, no pain. Score 2: no opening at the incision line, no drainage, mild swelling, mild pain. Score 3: no opening at the incision line, active drainage, advanced inflammation, moderate to advanced pain. Score 4: opening at the incision line, active drainage, advanced inflammation, ongoing pain. | 7 days after treatment | 
| Bone consolidation - baseline | Periapical radiography will evaluate the changes in the area of the defect (bone density). Periapical radiographs will always be performed with the same equipment using the parallelism technique. The area of the defect will be measured by multiplying the longest mesiodistal and supero-inferior diameters on the radiographs. In all radiographs, the longest diameter of the lesion was measured and the periapical index was evaluated. The periapical index was recorded according to the following parameters: 0 = no lesion, 1 = periapical radiolucency with a diameter of 0.5-1 mm, 2 = periapical radiolucency with a diameter of 1.1-2 mm, 3 = radiolucency periapical with a diameter of 2.1-4 mm, 4 = periapical radiolucency with a diameter of 4.1-8 mm and 5 = periapical radiolucency greater than 8.1 mm in diameter. | at baseline | 
| Bone consolidation - 24 hours after treatment | Periapical radiography will evaluate the changes in the area of the defect (bone density). Periapical radiographs will always be performed with the same equipment using the parallelism technique. The area of the defect will be measured by multiplying the longest mesiodistal and supero-inferior diameters on the radiographs. In all radiographs, the longest diameter of the lesion was measured and the periapical index was evaluated. The periapical index was recorded according to the following parameters: 0 = no lesion, 1 = periapical radiolucency with a diameter of 0.5-1 mm, 2 = periapical radiolucency with a diameter of 1.1-2 mm, 3 = radiolucency periapical with a diameter of 2.1-4 mm, 4 = periapical radiolucency with a diameter of 4.1-8 mm and 5 = periapical radiolucency greater than 8.1 mm in diameter. | 24 hours after treatment | 
| Bone consolidation - 7 days after treatment | Periapical radiography will evaluate the changes in the area of the defect (bone density). Periapical radiographs will always be performed with the same equipment using the parallelism technique. The area of the defect will be measured by multiplying the longest mesiodistal and supero-inferior diameters on the radiographs. In all radiographs, the longest diameter of the lesion was measured and the periapical index was evaluated. The periapical index was recorded according to the following parameters: 0 = no lesion, 1 = periapical radiolucency with a diameter of 0.5-1 mm, 2 = periapical radiolucency with a diameter of 1.1-2 mm, 3 = radiolucency periapical with a diameter of 2.1-4 mm, 4 = periapical radiolucency with a diameter of 4.1-8 mm and 5 = periapical radiolucency greater than 8.1 mm in diameter. | 7 days after treatment |