Medicaments Substances in Therapeutic Use Clinical Trial
Official title:
Preemptive Use of Etodolac on Tooth Sensitivity Caused by In-office Bleaching: a Randomized, Triple-blind, Controlled Clinical Trial
Objectives: This study will determine the effectiveness of preemptive administration of
etodolac on risk and intensity of tooth sensitivity caused by in-office bleaching using 35%
hydrogen peroxide.
Materials and Methods: Fifty patients will be selected for this triple-blind, randomized,
cross-over, placebo-controlled clinical trial. Etodolac (400 mg) or placebo will be
administrated in a single-dose 1 hour prior to bleaching procedure. The whitening treatment
with 35% hydrogen peroxide will be carried out in two sessions with a 7-day interval. Tooth
sensitivity will be assessed before, during and 24 hours after the procedure using analog
visual and verbal scales. Color alteration will be assessed by a bleach guide scale 7 days
after each session. Relative risk to sensitivity will be calculated and adjusted by session;
while comparison of overall risk will performed by McNemar's test. Data on the sensitivity
level for both scales and color shade will be subjected to the Friedman, Wilcoxon and
Mann-Whitney tests, respectively (α = 0.05).
Methods & Materials:
This clinical trial was approved by the Scientific Review Committee and by the Committee for
the Protection of Human Subjects of the local university (CAAE 37578714.4.0000.5546).
Trial design:
This study will be a randomized, triple-blind, placebo-controlled clinical trial with a
cross-over design. The patients included will be submitted to two in-office bleaching
sessions receiving placebo (control) or etodolac prior to the bleaching procedure; while
different treatments will be allocated for each session. A delay of 1 week between the
sessions (wash-out) will be established. The study will be conducted at the clinic of the
School of Dentistry of the local university from November 2014 to July 2015.
Participants:
Patients included in this clinical trial will be at least 18 years old with good oral
health. Patients with any of the six upper anterior teeth with caries, restoration, severe
discoloration (e.g., stains caused by tetracycline), enamel hypoplasia, gingival recession,
dentin exposure, pulpitis, or endodontics will be excluded. Participants submitted to
previous bleaching procedures, presenting prior tooth sensitivity, known allergy to any
component of medication used in the study, pregnant or breastfeeding will be also excluded.
Only patients presenting all six upper anterior teeth with shade mismatching with 2.5 M2
(Vita Bleachguide 3D-Master scale, Vita-Zahnfabrik, Bad Sackingen, Germany) or darker will
be included.
Sample Size Calculation:
The sample calculation will be based on the primary binary outcome (sensitivity risk 24
hours after the procedure) for superiority trial. Power of the test will be set at 80%,
considering a type I error of 0.05; risk to tooth sensitivity of 90%, based on a prior study
using similar bleaching agent, while a reduction around 30% with the treatment will be
expected. The calculation resulted in fifty patients.
Randomization:
A randomized list will be computer-generated by a person not involved in intervention or
evaluation. The participants were defined as blocks in the randomization process, where the
sequence of treatment (placebo or etodolac) will be randomly set for each block by using
computer-generated tables (www.sealedenvelope.com). The sequence will be inserted into
sealed envelopes numbered from 1 to 50 that were opened by the operator only at the moment
of the intervention. The patients were numbered according to the sequence of enrollment.
Neither the participant nor the operator knew the group allocation determining blinding to
the protocol.
Baseline evaluation:
Prior to bleaching procedure, the teeth will be cleaned using rubber cups associated to
pumice and water. The shades of six upper anterior teeth will be assessed on a baseline
using the bleach guide scale. The color analysis will be carried out by two previously
calibrated evaluators. The two evaluators presented superior color matching competency
according to the ISO (International Organization for Standardization) 28642:2011. The
shades' tabs selected will be converted to scores ranging from 1 (whiter shade - 0M1) to 15
(darker shade - 5M3).
Considering a possible effect of dental anxiety on sensitivity reported by patients, the
Corah's Dental Anxiety Scale will be used to determine the level of anxiety of each patient
related to the procedure [26]. Each answer to the survey instrument will be scored on a
scale from 1 to 5 (four questions); and the sum of scores will be used to determine the
level of anxiety: low will be lower than 12, moderate will be between 12 and 14, and high
will be higher than 14.
Intervention:
One-hour prior to each bleaching session, the patients will receive a capsule containing 400
mg of NAISE etodolac or 400mg of placebo (inert content), according to the randomization,
while the capsules will present the same appearance. The capsules with similar presentation
will be manufactured by a person not involved in intervention or evaluation and will be
placed into two bottles identified by letters according to treatment. Neither the operators
responsible for intervention and evaluation nor the patients knew the content of each
capsule.
A light-cured resin dam will be applied (Top Dam, FGM, Joinville, SC, Brazil) on the
gingival tissue corresponding to the teeth to be bleached. A 35% hydrogen peroxide based
bleaching agent (Whiteness HP Blue, FGM, Joinville, SC, Brazil) will be mixed and applied on
the vestibular surface of teeth, remaining for 40 minutes. After this time, the bleaching
agent will be removed. A second session will beas carried out after 1 week following the
same procedures. At this time, the patient received a single-dose capsule containing
etodolac or placebo (different from the ones received at first session) 1 hour before the
procedure.
Evaluations:
The tooth sensitivity reported by patients will be assessed using a visual analog scale
(VAS) and verbal rating scale (VRS). The VAS consisted of a scale 10 cm in length ranging
from green (absence of pain) to red (unsupportable pain). The patient set his or her level
of sensitivity by pointing to the color corresponding to this level, while the distance from
this point to the green border will be recorded. For VRS, the patient reported his or her
level of sensitivity based on scores: 0 = none, 1 = light, 2 = moderate, 3 = considerable
and 4 = severe. The tooth sensitivity will be assessed during the bleaching, immediately
after bleaching agent removal and after 24 hours. For this last assessment, only the VRS
will be used. One week after each session the tooth color will be evaluated again using the
same procedure described previously.
Statistical Analysis:
The demographic data from patients will be analyzed to determine age, gender, and anxiety
level for each allocation sequence. Comparisons between the allocation sequences will be
performed by the Mann-Whitney test (age) and Fisher's exact (gender) and chi-square (anxiety
level) tests.
Based on presence of any tooth sensitivity (scores different from 0 for VRS), the absolute
risk, odds ratio and relative risk will be calculated regarding the treatments for each
moment of evaluation/session of bleaching, as well as its confidence intervals (95%). For
each moment, differences on presence/absence ratios will be analyzed by Fisher's exact test.
For the overall risk related to each treatment, the odds ratio will be adjusted to
independent variable "session of bleaching" using the Mantel-Haenszel statistic. The
homogeneity of odds ratios will be analyzed by the Breslow-Day and Tarone's tests.
Following, the odds ratio estimated will be converted to relative risk and the overall
presence/absence ratios will be analyzed by the McNemar's test, considering the study design
(cross-over).
For VRS, the data from scores observed in each time of evaluation/session of bleaching will
be submitted to the Mann-Whitney rank sum test. Despite the measurement of tooth sensitivity
using VAS giving a continuous outcome, data assessed with this scale did not show a normal
distribution (Shapiro-Wilk's test). Thus, data from VAS will be also analyzed by the
Mann-Whitney rank sum test, while one test per time of evaluation will be carried out.
For color evaluation, comparisons between the sequences of treatment will be performed using
the Mann-Whitney rank sum test. The Friedman test followed by Dunn's post hoc test will be
used to analyze the difference between the moments of evaluation for each sequence of
treatment. All statistical analyses will be performed adjusting the initial significance
level (α = 0.05) by Bonferroni correction.
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
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