Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03501225 |
| Other study ID # |
23032018 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
March 28, 2018 |
| Last updated |
April 16, 2018 |
| Start date |
November 8, 2017 |
| Est. completion date |
March 23, 2018 |
Study information
| Verified date |
January 2018 |
| Source |
Federal University of the Valleys of Jequitinhonha and Mucuri |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The aim of this study was to evaluate the effect of ozonated water on pain, edema and trismus
after third molar removal. Patients were submitted to extraction of lower third molar under
irrigation with ozonated water or doubly distilled water. Data were collected at baseline, 24
hours, 48 hours, 72 hours and 7 days after intervention.
Description:
The intensity of pain, the degree of edema and trismus are generally subjective and difficult
to show a variation between patients. To detect this difference, we chose a split-mouth study
design - one side will be assigned irrigation with ozonated water (Study Group) and the
contralateral side will be assigned irrigation with double-distilled water (control group) in
which each patient will be self-controled. The control side and the study side were assigned
to the same patient to exclude bias from individual variations. Bias in the sample selection
and evaluation of the parameters will be decreased by randomization and blinding,
respectively.
Recently Resolution Conselho Federal de Odontologia (CFO) 166/2015 recognized the practice of
ozone therapy by the dental surgeon. It is necessary to search for more robust and consistent
results so that a careful analysis may or may not justify the routine use of ozone as a
treatment modality in dentistry.
There have been no reports in literature of studies that evaluated the effects of ozonation
(ozonated water), pain control, edema, trismus and quality of life, with blinding of
patients, operators and evaluators, after extraction of mandibular third impacted molars.
Therefore, this trial is justified in the search for new alternatives with fewer side effects
in the control of postoperative complications and in the realization of a triple blind
randomized clinical trial on the application of ozone in dentistry.
The main objective to evaluate the effect of the use of ozonated water on irrigation
performed in bilaterally impacted and asymptomatic inferior third molars.
The secondary objectives to evaluate the quality of life in patients submitted to bilaterally
impacted and asymptomatic inferior third molars and compare postoperative pain, trismus and
edema in the group using ozonated water with the control side.
METHODOLOGY Study Design
A triple blind randomized controlled trial was conducted.
Location of study
Clinic of Surgery and Periodontics of the Universidade Federal dos Vales do Jequitinhonha e
Mucuri (UFVJM) / Diamantina /Minas Gerais (MG)
Ethical Principles
According to resolution CNS / 12, the research project was submitted and approved by the
Comitê de Ética em Pesquisa (CEP) / UFVJM (opinion nº: 2.174.074) and the study was developed
according to the protocols of CONSORT.
In accordance with resolution 466 Conselho Nacional de Saúde (CNS), a presentation /
explanation letter was sent to all participants, describing the main points involved in the
research. Participants who agreed to the terms of the study and signed the informed consent
form (TCLE-ANNEX I) were included. All participants were guaranteed surgery for extraction of
lower third molars. We used the split-mouth study model (in which the patient is
self-controlled), in order to exclude bias from individual variations. On one side ozonated
water (as irrigating solution) was applied and on the other side, after a period of 4 weeks,
double distilled water (as irrigating solution).
Sample Lectures were held about the Research Project at Tiradentes High School and Ayna
Torres High School. The interested parties provided the necessary data and were later called
to UFVJM for a clinical and radiographic examination.
Sample size
Sample calculation size for mean comparison (Lwanga & Lemeshow, 1991), considered the
standard deviation of pain 3,32 mm (kazancioglu et al.) And the difference to be detected
between groups stipulated in 3 mm, 95% significance and test power 80%, determining 19
patients. It was defined that 21 patients would be treated to avoid possible losses.
Randomization and concealment of the allocation
All extractions were pre-scheduled from January to February 2018. After establishing the
inclusion and exclusion criteria, we selected 21 patients who were scheduled according to
their availability for the day and time pre-established (3 surgeries per day, Monday and
Tuesday in the morning: 7.30, 8.30 and 9.30). When the agenda was completed, each patient was
numbered (from 1 to 21).
An independent team, (JNS) was responsible for randomization, and concealment of allocation.
The definition of which irrigating solution (double-distilled water or ozonated water) would
be Protocol I or Protocol II
- the words: Protocol I and Protocol II were placed in an opaque envelope
- the words: Double-distilled Water and Ozonized Water were placed in another opaque
envelope.
When making the draw it was defined that Protocol 1 would be OZONIZED WATER and obviously
Protocol 2 was with DOUBLE-DISTILLED WATER.
Note: the result of the draw was revealed after the conclusion of the statistic.
For the definition of the intervention to be Protocol I or Protocol II:
- the words: Protocol I and Protocol II were placed in an opaque envelope
- the odd numbers of a dice and the even numbers of a dice were placed in another opaque
envelope.
When making the draw it was defined that Protocol 1 would be any odd numbers of the dice and
obviously Protocol 2 was any even numbers of the dice.
For the definition of the intervention be on the right or left side:
- the words: right side and left side were placed in an opaque envelope
- the odd numbers of a dice and the even numbers of a dice were placed in another opaque
envelope.
When making the draw it was defined that the right side would be any odd numbers of the dice
and obviously the left side got any even numbers of the dice.
Thus, the data was released twice for each patient. The first release corresponding to the
protocol and the second release corresponding to the side to be operated. Each patient
received two envelopes. For the first surgery (sequence of patients established by the
schedule of surgeries), the protocol was raffled and soon after the side to be operated on
was also raffled; the result was placed inside the envelope (opaque) that was duly identified
with the patient's number, date, day and time (from surgery). The opposite result of the
first draw was placed on the second envelope. This procedure was performed in the same way
for the other 20 patients. Treatment allocation was kept secret (sealed / opaque envelopes),
stored sequentially in a closet and opened only 5 minutes before each surgery in the
preparation environment of the irrigating solution (Double-distilled Water and Ozonized
Water).
Masking of:
- Patient: was facilitated by the fact that the procedure was performed in the mouth so
the surgical tray was out of sight and the patient was wearing the peck cloth.
- Operator I (JCRG) and Assistant I (APSJ): They were "blinded" to treatment protocols (I
or II). When it was time to use the irrigating solution (the JNS helper), it was taken
to the surgical environment (protocol I or protocol II) in a stainless steel tank and it
is poured into another stainless steel tank in the surgical tray.
- Assistant II (LDAS): performed all the measurements and applied the questionnaires,
without knowing the protocols (I or II).
- Statistical (DWDO): Completed the database with all measurements and questionnaires
without knowing the protocols (I or II).
Variables:
dependent variables: ozone therapy (ozonated water)
Independent variables:
A 10-sheet block containing a sequence of medications related to pain, edema and trismus was
prepared for each patient. Each sheet contains the following published data: patient name,
age, gender, protocol, operational side and intervention timeline, time, day of the week and
data. The series was completed by Assistant II (LDAS), and there were spaces related to
evaluation of edema and evaluation of buccal opening in the whole block (baseline, 24, 48, 72
hours and 7 days postoperatively) and space for evaluation of operative pain at 24, 48, 72
hours post-operatively. The measurements were individually formed, detached and placed inside
one envelope so that there was influence on the result of the other.
Postoperative pain:
In order to evaluate the incidence and intensity of postoperative pain, a token was used with
a visual analogue scale consisting of a horizontal line of 10 cm, with no demarcations
presenting in the left extremity no pain (0), and right extremity the maximum of pain(10)
(ANNEX III). The patients were instructed to mark with a vertical trace the point of the
scale that best defines their degree of pain sensitivity after the surgical procedures (24,
48 and 72 hours). This marking was measured with a digital caliper (Mitutoyo® / taking into
account two decimal places) by the statistician when the data was released.
Presence of edema (postoperative):
The level of facial swelling (edema) was determined by measuring with measuring tape
according to the method described by angulation [27] (Photo 1). Three measures (1.
measurement of the corner of the eye to the angle of the mandible, 2. measurement of the
tragus at the corner of the mouth and 3. measurement of the tragus to the pogonion) were
performed between the 5 reference points: tragus, pogonion lateral corner of eyes, jaw angle,
outer corner of mouth. The measurements were obtained preoperatively (baseline) and in the
postoperative period of 24, 48 and 72 hours and 7 days. The sum of the preoperative
measurements will be the standard of normality for each side. After verification of the
measurements in the postoperative period, the difference in the measurements before and after
the surgical procedure was observed, determining the level of edema (APPENDIX IV).
Presence of trismus:
The maximum buccal opening will be used to assess the presence of trismus. The maximum
interincisive distance was measured by the assistant II (LDAS), through a digital caliper
(Mitutoyo® / taking into account two decimal places) and transcribed in millimeters for data
recording. The measurement was made considering the distance between the incisal face of the
right upper central incisor and the right lower central incisor after the maximum possible
opening of the mouth, in the preoperative (baseline) and in the postoperative period of 24,
48 and 72 hours and 7 days. The amount of reduction of the buccal opening was measured,
compared to the baseline. Thus, we calculated the relative mean between patients (Delta)
Quality of life:
After surgery, patients received the first questionnaire (Table 1) and were instructed to
take it home and fill it out through the course of the week. Seven days after the surgery,
the sutures were removed and the questionnaire filled with information on postoperative
quality of life was collected. At that time, another questionnaire (Table 2) was completed by
the patient at the clinic, after sutures were removed.
Surgery time:
The duration of the surgery was calculated through the use of a stopwatch, from the moment
the incision was made until the suture. (JCRG)
Patient-related variables:
Gender, age.
Treatments
Pharmacological:
Sodium Dipyrone 500 mg and Nimesulide 100 mg
- Redistilled water (closed system of 250 ml / sterile and pyrogenic): Sanobiol
laboratory.
- ozonated water (8.0 μg / ml): obtained by ozone generator philozon / medplusv, Brazil -
recognized by Anvisa, coupled to the glass column with catalytic converter and
microbubble diffuser in stainless steel tube. According to Nogales CG et al (2014),
water (double-distilled) does not absorb all the concentration offered to it. This ratio
is between 20 and 25% absorption. In this sense, the ozone generator was regulated at
40mcg (40 μg/ml) for 5 (five minutes) of bubbling in 250 ml of doubly distilled water to
obtain 8.0 μg / mL ozone / water concentration. An ozonated water was prepared for each
surgery and used immediately.
Surgical procedure Antisepsis and local anesthesia
For the extraoral antisepsis we used an alcoholic solution of 10% polyvinylpyrrolidone-iodine
(PVP-I). For local anesthesia, the technique of regional inferior and lingual alveolar nerve
block was used, with complementation of the buccal nerve anesthesia, with the care of slow
injection of the solution, after negative aspiration. For each surgery a maximum volume of up
to 5.4 mL of local anesthetic solution containing 2% lidocaine and 1: 100,000 epinephrine
(equivalent to 3 tubes of a local anesthetic solution) was used.
Surgical intervention The surgical procedures were performed in two sessions, with a 30-day
interval for each side of the hemimandible and the choice of the side to be operated in the
first session was random. Mandibular third molar surgeries were performed by a professional
with experience in this type of intervention and he was blind as to the type of treatment
that the patient underwent.
The surgical technique used for all cases can be described as follows: after incision of
Avellanal (1946) with a scalpel blade number 15 and separation of soft tissues for surgical
site exposure, a low rotation osteotomy (30,000 rpm) was performed with drill bit 8 mounted
on straight handpiece and high-speed drill 350,000 rpm with 702 C KG Sorensen carbide drills
mounted on a Dabi Atlante® high-speed handpiece at 350,000 rpm under constant irrigation with
(double-distilled water or ozonated water according to randomization) .
Then, the tooth extraction was performed with the aid of straight elevators of the Seldin
type, careful curettage, bone regularization and cleaning of the surgical area by means of
abundant irrigation with (double-distilled water or ozonated water according to the
randomization). The suture was performed with silk thread (4.0) through isolated stitches.
Hand-irrigation of double-distilled water or ozonated water (packed in small steel vats) was
performed with the use of a 10cc hypodermic glass syringe (ruthe brand) attached to a 10mm
(BD mark) steel needle.
The patients were re-evaluated (24.48.72 hours and 7 days for edema and trismus and 24.48.72
hours for pain intensity) after surgery, by an investigator (assistant II / LDAS) who was
"blinded" about the type of intervention that the patient underwent. In addition to the
removal of the suture on the 7th day, this same researcher collected and applied the quality
of life questionnaires.
Biosafety procedures
National biosafety standards and recommendations were followed for both infection control and
waste disposal. Operator I was responsible for maintaining adequate infection control during
clinical examination and surgery procedures. The assistant II was responsible for the same
control in the postoperative evaluations. The researchers conducted the examinations and
evaluations wearing white clothing, hat, mask, white apron and disposable latex gloves. The
instruments used were sterilized by autoclave.
Data processing
The results were typed and organized into a database, using the software Statistical Package
for Social Science (SPSS), version 23.0. Processing included encoding, typing and editing
data. This process was performed by two people, (one typed the data and the other checked the
data that was typed). Each envelope containing the data of each patient received a
corresponding number in the database.
Statistical analysis of data
A descriptive analysis was performed of the absolute and relative frequencies of all the
variables studied and the association tests. The data according to the different types of
intervention will be analyzed through the t-student test and the Wilcoxon test. The level of
significance will be p ≤ 0.05.
