IN-OFFICE TOOTH BLEACHING WITH 37% CARBAMIDE PEROXIDE
Condition: Tooth Sensitivity
MeSH terms: Dentin Sensitivity
Study type: Interventional
Phase: Phase 3

Summary: 
      Objectives: This study will determine the clinical efficacy of bleaching agent 37% carbamide
      peroxide compared to 35% hydrogen peroxide on the change of color scores in anterior superior
      teeth, in-office bleaching technique after 7, 14 and 37 days; and the Risk to the tooth
      sensitivity before, during and 24 hours after the procedure.

      Materials and Methods: Fifty patients will be selected for this single-blind, parallel,
      randomized-controlled clinical trial. The whitening treatment with 37% carbamide peroxide or
      35% hydrogen peroxide (control) will be carried out in a single application of 45 minutes for
      two sessions with a 7-day interval. The sensitivity level will be assessed before, during and
      24 hours after the procedure using verbal and analogic visual analogue (VAS) scales. Color
      alteration will be assessed by a bleach guide scale 7 days after each session and 30 days
      after the last 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 will be subjected to the Mann-Whitney tests (α = 0.05). The
      color change will be measured with a spectrophotometer using the CIE L * a * b * and the L*,
      a * and b * parameter delta data, and ΔE and Δ00, will be individually subjected to two-way
      repeated measures ANOVA test to compare the two bleaching techniques at each evaluation time
      (α = 0.05).
    

Detailed description: 
      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
      50511415.1.0000.5546).

      Trial design: This study will be a randomized-controlled, single-blind clinical trial with a
      parallel design. The patients included will be submitted to two in-office bleaching sessions
      with a 7-day interval receiving 35% hydrogen peroxide (control) or 37% carbamide peroxide in
      a single application of 45 minutes; while the same treatments will be allocated for each
      session. The study will be conducted at the clinic of the School of Dentistry of the local
      university from May 2016 to December 2016.

      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, pregnant or
      breastfeeding will be also excluded. Only patients presenting all six upper anterior teeth
      with shade mismatching with 2.5 M2 (Vita Bleach guide 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 continuous outcome for superiority
      control. Power of the test will be set at 80%, considering a type I error of 0.05; for a
      minimum detectable difference between treatments 25%, based on a prior study using similar
      bleaching agent, while a coefficient of variation of 30% of control treatment will be
      expected. The calculation resulted in fifty patients, through the formula used n = f(α/2, β)
      × [p1 × (100 - p1) + p2 × (100 - p2)] / (p2 - p1)2. 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 (treatment or control) 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 canine upper teeth will be assessed on a baseline with a
      spectrophotometer Vita EasyShade (Vita-Zahnfabrik, Bad Säckinge, Germany) using the CIE L * a
      * b *. 3 measurements on each tooth will be conducted, with the end result the average of 3
      values (L *, a * and b *).

      Intervention:

      Control treatment: 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 Maxx, FGM, Joinville, SC, Brazil) will be mixed
      and applied on the vestibular surface of teeth, in the ratio of 1 drop every 3 to the
      thickener and peroxide, remaining for 45 minutes. After this time, the bleaching agent will
      be removed. A second session will be as carried out after 1 week following the same
      procedures.

      Experimental Treatment: A 37% carbamide peroxide based bleaching agent (Power bleaching, BM4,
      Palhoça, SC, Brazil) will be applied on the vestibular surface of teeth with a relative
      isolation only using cotton roller, remaining for 45 minutes. After this time, the bleaching
      agent will be removed. A second session will be as carried out after 1 week following the
      same procedures.

      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 0
      (absence of pain) to 10 (unsupportable pain). The patient set his or her level of sensitivity
      by pointing on the scale corresponding to this level, while the distance from this point to
      the 0 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 and up to 24 hours after each session. One week after each session and 30 days
      after the last session the tooth color will be evaluated again using the CIE L * a * b * as
      previously described.

      Statistical Analysis:

      For color analysis, the parameter delta data L *, a * and b *, and ΔE and Δ00, will be
      individually subjected to two-way repeated measures ANOVA test to compare the two bleaching
      techniques at each evaluation time. 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 (parallel).

      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. All
      statistical analyses will be performed considering a 95% significance level (α = 0.05).
    

Intervention name(s): 37% Carbamide Peroxide; 35% hydrogen Peroxide
Intervention type(s): Drug; Drug
Intervention description(s): no Gingival dam protection (as manufacturer´s instruction)
37% Carbamide Peroxide application (2 sessions of 45 minutes)
Tooth sensitivity (Verbal and visual scale) and color evaluation; Gingival dam protection (as manufacturer´s instruction)
35% Hydrogen Peroxide application (2 sessions of 45 minutes)
Tooth sensitivity (Verbal and visual scale) and color evaluation
Intervention MeSH terms: Hydrogen Peroxide; Carbamide Peroxide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: Tooth Bleaching; Tooth Bleaching Agents; Tooth Whitening; Hydrogen Peroxide; Carbamide Peroxide