Trial Design, Settings, and Locations of Data Collection

This was a double-blind, controlled, parallel, randomized clinical trial, in which the evaluator and statistician were blinded to the group assignment. This study was performed from November 2016 to June 2017 at the Clinics of the School of Dentistry of the State University of Ponta Grossa, PR, Brazil.

Recruitment

Two weeks prior to the bleaching procedures, all of the volunteers–who sought treatment at the clinic of the dental school–received a dental prophylaxis with pumice and water in a rubber cup and signed an informed consent form. Recruitment was carried out by placing printed ads throughout the university.

Eligibility Criteria

Patients included in this clinical trial were at least 18 years old and had good oral and overall health. All patients underwent an exam of teeth and soft tissues, and there could be no changes such as cavities, dental wear, friction, visible cracks, gingivitis, periodontitis, or injuries. Participants were required to have six caries-free maxillary anterior teeth, with absence of any restorations or periodontal disease. The maxillary central incisors had to be shade A2 or darker, as judged by comparison with a value-oriented shade guide (Vita Classical, VITA Zahnfabrik, Bad Säckingen, Germany). Two calibrated investigators performed this evaluation, and they were required to have at least 85% agreement (Kappa statistic). The calibration process was performed before beginning the study evaluation.

Participants with prostheses, anterior restorations or dental braces, or severe internal tooth discoloration (tetracycline stains, fluorosis, and pulpless teeth) were not included in the study. Additionally, participants with any other pathology that could cause sensitivity (such as dentin exposure, recession, or the presence of visible cracks in the teeth); pregnant or breastfeeding women; smokers; people with bruxism; or participants who had previously undergone tooth-whitening procedures were also excluded.

Sample Size Calculation

The calculation of the sample size was based on the color variation (ΔE). A minimum of 58 participants was required to exclude a mean difference of 2.66 in ΔE (50%:50% acceptability threshold with a power of 90% and an alpha of 5%, considering that the standard deviation of ΔE is approximately 3.²⁴ To account for possible dropouts by patients, an additional 25% of the sample was added; therefore, the final calculation was 72 participants. This limit of equivalence (difference of means) was based on the fact that only an ΔE greater than 2.66 is considered clinically perceptible.

Randomization, Allocation, Concealment, and Blinding

Blocked randomization was used (block sizes of 2 and 4), and an equal allocation ratio was used to form the allocation list for the two comparison groups. The randomization list was prepared using software freely available online (www.sealedenvelope.com). Opaque, sealed, and consecutively numbered envelopes containing the identification of the groups were prepared by a third person, who was not involved in the research protocol. The envelopes were only opened immediately before the beginning of the bleaching procedure.

Participants and operators could not be blinded to the study groups, as they could easily identify the two protocols used. However, the evaluator who performed the color assessments and the statistician were blinded to the treatments. To maintain evaluator blinding, the two protocols–15 minutes (HP 15) and 30 minutes (HP 30) per day with 10% hydrogen peroxide (White Class, FGM, Joinville, SC, Brazil)–were explained to the patients by a researcher who was not an evaluator; the protocols were coded as either A or B. Only the research coordinator knew the coding system.

Study Intervention

Alginate impressions (Avagel, Dentsply, Petrópolis, Rio de Janeiro, Brazil) of each subject’s maxillary arch were made, and after disinfection with 2% glutaraldehyde for 10 minutes, these impressions were filled with dental stone (Asfer, Asfer Indústria Química Ltda., São Caetano do Sul, SP, Brazil). A 0.9-mm soft vinyl material (FGM, Joinville, SC, Brazil) was used to fabricate the custom-fitted tray that would hold the whitening gel in Plastivac P7 (BioArt, São Carlos, SP, Brazil). The excess material from the labial and lingual surfaces was trimmed to 1 mm from the gingival junction.

At this time, group assignments were revealed and each patient received the bleaching tray and their respective time-of-use protocol. All participants were instructed to wear the tray with the bleaching agent for 15 or 30 minutes (according to group allocation) once a day for 14 days. The participants were also instructed to remove the tray after each bleaching period and wash it with water.

As a measure of adherence to the experimental protocol, participants were given a diary in which they were asked to take note of the number of times they used the tray during the study. If they wore the bleaching tray 14 times, this would result in a 100% adherence to the protocol. Verbal instructions about oral hygiene were also provided, encouraging participants to brush their teeth regularly with fluoridated toothpaste containing no whitening components. There was no restriction in the diet of the volunteers.²⁵

Color Evaluation

Two calibrated evaluators recorded the shade of each subject’s teeth at baseline, during treatment (after the first and second week of bleaching treatment), and at one-month post-bleaching. In the event of disagreements between the examiners during shade evaluation, a consensus was reached through discussion. The color evaluation was performed using two value-oriented shade guide units: Vita Classical (VITA Zahnfabrik, Bad Säckingen, Germany)²⁶ and Vita Bleachedguide 3D-MASTER (VITA Zahnfabrik)^27–29 and with the aid of a spectophotometer (Easyshade, VITA Zahnfabrik).^18,26

For color evaluation with the Vita Classical scale, the 16 tabs of the shade guide were arranged from highest (B1) to the lowest (C4) value. Although this scale is not linear in the truest sense, for the purpose of analysis, the changes were treated as though they represented a continuous and approximately linear ranking.³⁰ The Vita Bleachedguide 3D-MASTER contains lighter shade tabs and is already organized from highest (0M1) to lowest (5M3) value.^31,32 The measurement area of interest for shade matching was the middle third of the facial surface of the anterior central incisor.³³ Color changes were calculated from the beginning of the active phase through to the individual recall times by calculating the change in the number of shade guide units (ΔSGU), which occurred toward the lighter end of the value-oriented list of shade tabs.

For color evaluation with the Vita Easyshade (VITA Zahnfabrik) spectrophotometer, an impression of the maxillary arch was taken with dense silicone paste (Speedex Putty, Coltene, Rio de Janeiro, Brazil). The impression was extended to the maxillary canine and served as a standard color measurement guide for the spectrophotometer. For each dental component evaluated, a window was created on the labial surface of the molded silicone guide using a metal device with a radius of 6 mm and well-formed borders.^7,29,31 The shade was determined using the parameters of the Easyshade device whereby the following values were indicated: L*, (a*), and (b*), where L* represented the value from 0 (black) to 100 (white) and a* and b* represented the shade, where a* was the measurement along the red-green axis and b* was the measurement along the yellow-blue axis. The color comparison before and after treatment was given by differences between the two colors (ΔE), which was calculated using the formula: ΔE=[(ΔL*)² + (Δa*)² + (Δb*)²]^1/2.³⁴ Despite the tooth color, measurements were performed for all maxillary anterior teeth (central and lateral incisors and canines); for statistical purposes, only the maxillary right central incisor was used. The measurement area of interest for shade matching was the middle third of the facial surface of the maxillary right central incisor.

Tooth Sensitivity Evaluation

All subjects were asked to keep a daily record of whether they experienced sensitivity. Each patient was asked to indicate the numerical value of the degree of sensitivity using a five-point Numeric Rating Scale (NRS) where 0 = none, 1 = mild, 2 = moderate, 3 = considerable, and 4 = severe.^29,35,36 The subjects were also asked to express their pain intensity using the Visual Analogue Scale 0–10 (VAS).^29,37,38 This scale is a 10-cm horizontal line with scores of 0 and 10 at each end, where 0 = no sensitivity and 10 = severe sensitivity. Patients marked a vertical line across the horizontal line of the scale that corresponded to the intensity of sensitivity. The distance in mm from the zero end was then measured with the aid of a millimeter ruler.

The worst score from the NRS scale and the highest numerical value obtained in the VAS scale during the entire bleaching treatment was considered for statistical purposes, in such a way that only a single value was taken from the two-week treatment period. The values were arranged into two categories: absolute risk of tooth sensitivity (TS), which represented the percentage of patients that reported TS at least once during treatment, and overall TS intensity.

Statistical Analysis

The analysis followed the intention-to-treat protocol and involved all participants who were randomly assigned (Figure 1).²³ In cases of missing data, the last observation was carried forward. The statistician was blinded to the study groups. The data were first analyzed using the Kolmogorov-Smirnov test to assess whether the data followed a normal distribution, as well as the Bartlett test for equality of variances to determine whether the assumption of equal variances was valid. After that, the absolute risks of bleaching-induced TS were determined using the Fisher exact test. The relative risk was calculated, as well as the confidence interval for the effect size. For comparison of TS intensity (NRS and VAS data) of the two groups, the worst score of the each group was calculated. After that, the Mann-Whitney test was applied. The color changes between groups (ΔSGU on both scales and ΔE) at each time point were compared using a Mann-Whitney U test. For the comparisons between times within each group, the Friedman test was applied. In all statistical tests, the significance level was 0.05. We performed all analyses by using SigmaPlot version 11.0 software (SPSS Inc, IBM, Armonk, NY, USA).

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Characteristics of Participants

In all, 121 volunteers were evaluated for selection of the study sample, and 72 participants met the study inclusion criteria (Figure 1). The patients were randomly divided into HP 15 (n=36) and HP 30 (n=36). The mean age of all participants was similar, and the majority of participants included in the sample were female (Table 1).

Table 1: Demographic Characteristics of the Participants

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Adherence to the Protocol

Adherence to the protocol was 86% for HP 15 and 78% for HP 30. Three participants did not attend the one-month recall visit–one in HP 15 and two in HP 30. For these participants, the last observation was carried forward for statistical purposes in order to maintain the intention-to-treat analysis.

Color Evaluation

Color change effectiveness of dental bleaching was verified through the mean and standard deviation of the ΔSGU using the subjective (Vita Classical and Vita Bleachedguide 3D-MASTER, VITA Zahnfabrik) and objective (spectrophotometer) scales, and through the ΔE values (Table 2) in the different evaluation periods (p<0.05). Whitening of approximately 3.3 to 4.8 ΔSGU (Vita Classical) and 3.9 to 6.9 ΔSGU (Vita Bleachedguide), and ΔE of approximately 6.6 to 9.0 were detected for both groups at one month after bleaching (Table 2). Although a significant whitening effect was observed after only two weeks of bleaching (p=0.01), no statistically significant difference was observed between the study groups at the different periods (p>0.06). For all color measurements, the mean difference ranged from −0.6 to 1.0 and was not clinically important (Table 2).

Table 2: Color Change in Shade Guide Units (ΔSGU) and ΔE at Different Bleaching Periods for the 2 Bleaching Protocols Along with the Effect Size (95% Confidence Interval)

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Tooth Sensitivity

There was no significant difference in tooth sensitivity between the groups evaluated (p=1.00) (Table 3). Hydrogen peroxide 10% applied for either 15 or 30 minutes per day produced a 47% risk of tooth sensitivity. Regarding the intensity of dental sensitivity (Table 3), there were no significant differences between the two groups analyzed with the two pain scales used for this study (Table 4; p>0.36).

Table 3: Comparison of the Number of Patients Who Experienced Tooth Sensitivity During the Bleaching Regimen in Both Groups Along with Absolute and Risk Ratio

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Table 4: Means (Standard Deviations) and Medians (Interquartile Range) of Worst Score of the Tooth Sensitivy Intensity Using the NRS and VAS Scales

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