Ignite Creation Date:
2024-05-06 @ 6:48 PM
Last Modification Date:
2024-10-26 @ 2:55 PM
Study NCT ID:
NCT05791721
Status:
COMPLETED
Last Update Posted:
2023-03-30
First Post:
2023-03-04
Brief Title:
Effect of Preemptive Etoricoxib and Dexamethasone on Wound Healing and Clinical Parameters After Third Molar Surgery
Sponsor:
University of Belgrade
Organization:
University of Belgrade
Study Overview
Official Title:
Preemptive Use of Etoricoxib and Dexamethasone Effect on Early Bone Healing Inflammatory Response and Postoperative Parameters After Impacted Lower Third Molar Surgery
Status:
COMPLETED
Status Verified Date:
2023-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this clinical trial is to compare preemptive single-dose selective cyclooxygenase 2 COX-2 inhibitor - etoricoxib and dexamethasone use in systemically healthy patients during the surgical extraction of impacted mandibular third molars The main questions it aims to answerevaluate are
the level of inflammatory and early wound healing mediators in patients saliva during early postoperative phase
clinical postoperative parameters such as pain swelling and trismus
patient satisfaction with the treatment
rescue medication consumed during the postoperative period
incidence of adverse events
Participants indicated for mandibular third molar surgery will be asked to
take premedication etoricoxib or dexamethasone before surgical extraction
provide saliva samples before and following the surgery at regular check-ups
note the amount of rescue medication taken and pain intensity in different time points
perform clinical measurements of swelling and trismus at regular check-up visits
answer the questions about satisfaction and potential adverse events if occur Researchers will compare preemptive single-dose etoricoxib preemptive single-dose dexamethasone and no premedication in impacted mandibular third molar surgery to see if there are differences in inflammatory response and early wound healing as well as in clinical postoperative parameters patient satisfaction with the treatment and incidence of potential adverse events
the level of inflammatory and early wound healing mediators in patients saliva during early postoperative phase
clinical postoperative parameters such as pain swelling and trismus
patient satisfaction with the treatment
rescue medication consumed during the postoperative period
incidence of adverse events
Participants indicated for mandibular third molar surgery will be asked to
take premedication etoricoxib or dexamethasone before surgical extraction
provide saliva samples before and following the surgery at regular check-ups
note the amount of rescue medication taken and pain intensity in different time points
perform clinical measurements of swelling and trismus at regular check-up visits
answer the questions about satisfaction and potential adverse events if occur Researchers will compare preemptive single-dose etoricoxib preemptive single-dose dexamethasone and no premedication in impacted mandibular third molar surgery to see if there are differences in inflammatory response and early wound healing as well as in clinical postoperative parameters patient satisfaction with the treatment and incidence of potential adverse events
Detailed Description:
Acute pain swelling and trismus present typical clinical manifestation following impacted mandibular third molar surgery Postoperative wound healing is regulated by activity of inflammatory mediators and osteogenic factors Nonsteroidal anti-inflammatory drugs especially cyclooxygenase 2 COX-2 inhibitors and glucocorticoids are routinely used to improve postoperative clinical state of the patients Studies have shown that both COX-2 inhibitors and dexamethasone may decrease the number of postsurgical rescue medication intake reduce the postoperative edema and increase the mouth opening ability Analgesic efficacy of etoricoxib ETOX a high selective COX-2 inhibitor has been shown as superior compared to placebo and other nonsteroidal anti-inflammatory drugs in third molar surgery However literature data on comparative testing of ETOX and dexamethasone DEX use in third molar surgery are scarce Furthermore no studies with a 7 days follow-up were conducted Preclinical studies indicate that COX-2 inhibitors and DEX may negatively affect early wound healing by down-regulation of mediators such as COX-2 prostaglandin E2 PGE2 alkaline phosphatase ALP runt-related transcription factor 2 RUNX2 and osteocalcin OCN Specialized pro-resolving lipid mediators are important for resolution phase of inflammatory process and wound healing According to animal studies maresin 1 MAR1 has important role in post-trauma pain reduction and bone healing thus the expression of this mediator may be significant to indicate the course of postoperative wound healing In the current literature no data on salivary early bone healing mediators following preemptive use of ETOX and DEX in mandibular third molar removal are available Moreover the correlation of these markers as well as inflammatory saliva mediators with the clinical parameters may be important for potential developing of future unique protocols for premedication in third molar surgery
The primary goal of the research will be to evaluate the level of inflammatory and early wound healing mediators COX-2 PGE2 ALP RUNX2 OCN MAR1 in saliva samples obtained from the systemically healthy patients requiring impacted mandibular third molar extraction in conditions of 1-preemptive single-dose ETOX 90 mg oral use 2-preemptive single-dose DEX 4 mg intramuscular use and 3-no premedication Secondary outcomes will include correlation of mentioned salivary mediators with postoperative clinical parameters such as pain swelling and trismus Furthermore rescue medication intake patient satisfaction with the treatment and incidence of potential adverse events will be recorded
A prospective randomized controlled parallel-group double-blinded clinical trial will be conducted at the Department of Oral surgery and Laboratory for basic science School of Dental medicine University of Belgrade Serbia The research will be performed following the CONSORT guidelines per the Helsinki Declaration Subjects who require unilateral fully impacted mandibular third molar extraction will be screened for eligibility After meeting the inclusion criteria participants will receive verbal and written information on the study objectives protocol as well as the possible risks and benefits of the study Only the eligible subjects who agree with the information provided and sign an informed consent form will be enrolled in the study A total of 90 patients will be included n30 Computer-generated blocked randomization with a 111 allocation ratio block size 6 will be performed by a researcher not included in the study Microsoft Excel version 2016 To conceal the allocation the papers containing a code of the allocated group 1-ETOX group 2-DEX group 3-control group will be sequentially packed in opaque envelopes and sealed One hour before the intervention the same independent researcher will unseal the following envelope and depending on the study group administer ETOX in a blurred plastic container ETOX group DEX in the unspecified syringe DEX group or provide written information on cold packs usage during the postoperative period control group The patients will be unaware of the generic and the brand name of the medications but they will be notified that the drugs are registered and on the market The allocation will be concealed until the finishing of the data analysis The surgeon who will perform all the interventions and the researcher who will collect the data will be masked to the patients allocations
After recruitment data on age years sex and smoking status no smoking 10day or 10day will be obtained from all the included patients During the same visit the surgical intervention will be scheduled and the third molar position will be estimated on panoramic radiographs according to the Pell and Gregory and Winter classifications Initial exam pre- perioperative and follow-up measurements will be performed by one blinded clinician
On the second study visit one hour before surgical intervention patients will be instructed to note the amount of pain experienced at that moment on a 10-cm long visual analog scale VAS where 0 means no pain at all and 10 represent the greatest pain they ever felt A 6-point verbal rating pain scale VRS will be also provided to the patients to document the current pain 1-no pain 2-mild pain 3-moderate pain 4-severe pain 5-very severe pain 6-the worst possible pain Additionally baseline measurements of a maximal inter-incisor and lobule-pogonion distance at the side of the extraction-required third molar in millimeters will be obtained by a soft tape measure Afterward 1 hour before the surgery patients will receive single-dose ETOX 90 mg Etoxib KRKA Novo Mesto Slovenia orally ETOX group single-dose DEX 4 mg Dexason Galenika Belgrade Serbia in deltoid muscle DEX group no premedication control group
After regional inferior alveolar lingual and buccal nerve blocks with a local anesthetic consisting of 4 articaine hydrochloride with 1100000 epinephrine Septanest Septodont Saint-Maur-des-Fosses France the surgical removal of impacted mandibular third molar will be performed according to the technique previously described in the literature after full-thickness flap elevation bone removal will be performed by rotatory instruments under sterile saline irrigation Instruments such as levers will be used for tooth extraction and tooth separation will be performed if necessary After tooth extraction and bone edges smoothening the wound will be primary sutured All the surgical procedures will be performed by one experienced oral surgeon masked to the allocation group Perioperatively the duration of the intervention min the amount of local anesthetic solution used ml tooth separation if performed and any complications such as inferior alveolar vascular damage will be registered
Following the intervention patients will be advised to take rescue medication if pain occurs at any time Paracetamol 500 mg regimen will be prescribed as an escape analgesic Paracetamol Galenika Belgrade Serbia with the instructions to not exceed the maximal recommended daily dose 4000 mg Additionally the antibiotics will be prescribed amoxicillin 500 mg or clindamycin 600 mg in case of penicillin hypersensitivity three times a day for 5 days Thereafter all the patients will receive written hygienic-dietary instructions with the advice of careful oral hygiene maintenance a soft diet avoidance of mouth rinsing as well as smoking hot food and hot beverages The additional penned information for the control group will involve repeated use of cold packs with a 20-min pause and will be submitted to the patients preoperatively
After surgery patients will received a pre-designed take-home diary containing fields for rescue analgesic registration every time of intake number of the regimen and dose and a list of the most common adverse events headache nausea vomiting vertigo insomnia fever with instructions to check any of the listed or write down any other if occurred Additionally patients will be instructed to record pain intensity on VAS and VRS at 2h 4h 6h 8h 10h 12h and 72h following the surgery as well as in every case of rescue medication intake
Control check-ups will be scheduled at 24h 48h and 7 days postoperatively On each control examination the 5-point Likert scale will be used to assess patient satisfaction at the respective time The following question will be asked How satisfied are you at this moment with the impacted mandibular third molar surgery and the possible answers will be 5-very satisfied 4-satisfied 3-neutral 2-dissatisfied and 1-very dissatisfied After collecting the answers from every check-up visit average patient satisfaction with the treatment will be calculated During every control study visit the severity of pain experiencing at that moment will be noted on VAS and VRS Maximal inter-incisor and lobule-pogonion distance on the operated side will be measured In addition at a 7-day check-up the take-home diary will obtained from the patients
Samples containing 05 ml of unstimulated saliva will be collected from the floor of the mouth by means of 2 ml plastic syringe and dull needle of 18 Gauge thickness in four time points One hour before surgery immediately 48h and 7 days after the surgery Saliva samples will be collected in sterile plastic tubes that are pre-filled with fluid that prevents RNA degradation and stored at -80 degrees Celsius until laboratory analysis
Laboratory procedures will be performed with aim to assess the level of relative gene as well as protein expression of inflammatory COX-2 PGE2 and early wound healing RUNX2 ALP OCN MAR1 mediators in tested groups in different time points of interest After RNA isolation and obtaining of complementary DNA according to the manufacturer instructions relative gene expression of COX-2 PGE2 RUNX2 ALP and OCN will be evaluated by means of real-time polymerase chain reaction assay Protein expression of PGE2 and MAR1 will be performed by enzyme linked immunosorbent assay ELISA
Statistical analysis will be performed in statistical package SPSS version 220 SPSS Inc Chicago Data will be presented through mean standard deviation median maximum and minimum values percent Depending of the data distribution appropriate parametric or non-parametric tests will be performed Regression models will be performed to determine the predictors of detected inter-group differences The level of significance will be set at 005
The primary goal of the research will be to evaluate the level of inflammatory and early wound healing mediators COX-2 PGE2 ALP RUNX2 OCN MAR1 in saliva samples obtained from the systemically healthy patients requiring impacted mandibular third molar extraction in conditions of 1-preemptive single-dose ETOX 90 mg oral use 2-preemptive single-dose DEX 4 mg intramuscular use and 3-no premedication Secondary outcomes will include correlation of mentioned salivary mediators with postoperative clinical parameters such as pain swelling and trismus Furthermore rescue medication intake patient satisfaction with the treatment and incidence of potential adverse events will be recorded
A prospective randomized controlled parallel-group double-blinded clinical trial will be conducted at the Department of Oral surgery and Laboratory for basic science School of Dental medicine University of Belgrade Serbia The research will be performed following the CONSORT guidelines per the Helsinki Declaration Subjects who require unilateral fully impacted mandibular third molar extraction will be screened for eligibility After meeting the inclusion criteria participants will receive verbal and written information on the study objectives protocol as well as the possible risks and benefits of the study Only the eligible subjects who agree with the information provided and sign an informed consent form will be enrolled in the study A total of 90 patients will be included n30 Computer-generated blocked randomization with a 111 allocation ratio block size 6 will be performed by a researcher not included in the study Microsoft Excel version 2016 To conceal the allocation the papers containing a code of the allocated group 1-ETOX group 2-DEX group 3-control group will be sequentially packed in opaque envelopes and sealed One hour before the intervention the same independent researcher will unseal the following envelope and depending on the study group administer ETOX in a blurred plastic container ETOX group DEX in the unspecified syringe DEX group or provide written information on cold packs usage during the postoperative period control group The patients will be unaware of the generic and the brand name of the medications but they will be notified that the drugs are registered and on the market The allocation will be concealed until the finishing of the data analysis The surgeon who will perform all the interventions and the researcher who will collect the data will be masked to the patients allocations
After recruitment data on age years sex and smoking status no smoking 10day or 10day will be obtained from all the included patients During the same visit the surgical intervention will be scheduled and the third molar position will be estimated on panoramic radiographs according to the Pell and Gregory and Winter classifications Initial exam pre- perioperative and follow-up measurements will be performed by one blinded clinician
On the second study visit one hour before surgical intervention patients will be instructed to note the amount of pain experienced at that moment on a 10-cm long visual analog scale VAS where 0 means no pain at all and 10 represent the greatest pain they ever felt A 6-point verbal rating pain scale VRS will be also provided to the patients to document the current pain 1-no pain 2-mild pain 3-moderate pain 4-severe pain 5-very severe pain 6-the worst possible pain Additionally baseline measurements of a maximal inter-incisor and lobule-pogonion distance at the side of the extraction-required third molar in millimeters will be obtained by a soft tape measure Afterward 1 hour before the surgery patients will receive single-dose ETOX 90 mg Etoxib KRKA Novo Mesto Slovenia orally ETOX group single-dose DEX 4 mg Dexason Galenika Belgrade Serbia in deltoid muscle DEX group no premedication control group
After regional inferior alveolar lingual and buccal nerve blocks with a local anesthetic consisting of 4 articaine hydrochloride with 1100000 epinephrine Septanest Septodont Saint-Maur-des-Fosses France the surgical removal of impacted mandibular third molar will be performed according to the technique previously described in the literature after full-thickness flap elevation bone removal will be performed by rotatory instruments under sterile saline irrigation Instruments such as levers will be used for tooth extraction and tooth separation will be performed if necessary After tooth extraction and bone edges smoothening the wound will be primary sutured All the surgical procedures will be performed by one experienced oral surgeon masked to the allocation group Perioperatively the duration of the intervention min the amount of local anesthetic solution used ml tooth separation if performed and any complications such as inferior alveolar vascular damage will be registered
Following the intervention patients will be advised to take rescue medication if pain occurs at any time Paracetamol 500 mg regimen will be prescribed as an escape analgesic Paracetamol Galenika Belgrade Serbia with the instructions to not exceed the maximal recommended daily dose 4000 mg Additionally the antibiotics will be prescribed amoxicillin 500 mg or clindamycin 600 mg in case of penicillin hypersensitivity three times a day for 5 days Thereafter all the patients will receive written hygienic-dietary instructions with the advice of careful oral hygiene maintenance a soft diet avoidance of mouth rinsing as well as smoking hot food and hot beverages The additional penned information for the control group will involve repeated use of cold packs with a 20-min pause and will be submitted to the patients preoperatively
After surgery patients will received a pre-designed take-home diary containing fields for rescue analgesic registration every time of intake number of the regimen and dose and a list of the most common adverse events headache nausea vomiting vertigo insomnia fever with instructions to check any of the listed or write down any other if occurred Additionally patients will be instructed to record pain intensity on VAS and VRS at 2h 4h 6h 8h 10h 12h and 72h following the surgery as well as in every case of rescue medication intake
Control check-ups will be scheduled at 24h 48h and 7 days postoperatively On each control examination the 5-point Likert scale will be used to assess patient satisfaction at the respective time The following question will be asked How satisfied are you at this moment with the impacted mandibular third molar surgery and the possible answers will be 5-very satisfied 4-satisfied 3-neutral 2-dissatisfied and 1-very dissatisfied After collecting the answers from every check-up visit average patient satisfaction with the treatment will be calculated During every control study visit the severity of pain experiencing at that moment will be noted on VAS and VRS Maximal inter-incisor and lobule-pogonion distance on the operated side will be measured In addition at a 7-day check-up the take-home diary will obtained from the patients
Samples containing 05 ml of unstimulated saliva will be collected from the floor of the mouth by means of 2 ml plastic syringe and dull needle of 18 Gauge thickness in four time points One hour before surgery immediately 48h and 7 days after the surgery Saliva samples will be collected in sterile plastic tubes that are pre-filled with fluid that prevents RNA degradation and stored at -80 degrees Celsius until laboratory analysis
Laboratory procedures will be performed with aim to assess the level of relative gene as well as protein expression of inflammatory COX-2 PGE2 and early wound healing RUNX2 ALP OCN MAR1 mediators in tested groups in different time points of interest After RNA isolation and obtaining of complementary DNA according to the manufacturer instructions relative gene expression of COX-2 PGE2 RUNX2 ALP and OCN will be evaluated by means of real-time polymerase chain reaction assay Protein expression of PGE2 and MAR1 will be performed by enzyme linked immunosorbent assay ELISA
Statistical analysis will be performed in statistical package SPSS version 220 SPSS Inc Chicago Data will be presented through mean standard deviation median maximum and minimum values percent Depending of the data distribution appropriate parametric or non-parametric tests will be performed Regression models will be performed to determine the predictors of detected inter-group differences The level of significance will be set at 005
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None