Piroxicam-beta-Cyclodextrin on Tooth Sensitivity Caused by In-office Bleaching
Condition: Tooth Sensitivity; Toothache
MeSH terms: Dentin Sensitivity; Toothache; Hypersensitivity
Study type: Interventional
Phase: Phase 3

Summary: 
      Objectives: This study aims to evaluate the effectiveness of preemptive administration of
      non-steroidal anti-inflammatory Piroxicam-beta-Cyclodextrin on risk and level of tooth
      sensitivity caused by in-office bleaching procedures using 35% hydrogen peroxide.

      Fifty patients will be selected for this triple-blind, randomized, cross-over,
      placebo-controlled clinical trial. Piroxicam-beta-Cyclodextrin (200 mg) or placebo will be
      administrated in a single-dose thirty minutes 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 Immediately before bleaching agent removal and
      up to 24 hours after each session 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 Fisher's exact test. Data on the sensitivity level for both scales and
      color shade will be subjected to the Mann-Whitney and Friedman tests, respectively (α =
      0.05).
    

Detailed description: 
      Methods & Materials:

      This clinical trial was approved by the Scientific Review Committee and by the Ethics
      Committee on Research Involving Humans at the University Hospital of the Federal University
      of Sergipe (CAAE 50511415.1.0000.5546).

      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 Piroxicam-beta-Cyclodextrin 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 December 2016 to May 2017.

      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 lesions, restoration, severe
      discoloration (e.g., stains caused by tetracycline), fluorosis, gingival recession, dentin
      exposure, periodontal diseases, pulpitis, or endodontics treatment will be excluded.
      Participants submitted to previous bleaching procedures, presenting prior tooth sensitivity,
      known allergy to any component of medication used in the study, Continuous use of drugs with
      anti-inflammatory actions, 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 piroxicam-beta-cyclodextrin) 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 (Vita Bleach Guide,Vita-Zahnfabrik, Bad Säckinge, Germany). The
      shades' tabs selected will be converted to scores ranging from 1 (whiter shade - 0M1) to 15
      (darker shade - 5M3).

      Intervention:

      Thirty minutes prior to each bleaching session, the patients will receive a capsule
      containing 20mg of piroxicam-beta-cyclodextrin or 20mg 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 Maxx, FGM, Joinville, SC, Brazil) will be mixed and applied on the
      vestibular surface of teeth, remaining for 45 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
      piroxicam-beta-cyclodextrin or placebo (different from the ones received at first session)
      thirty minutes before the procedure.

      Evaluations:

      The tooth sensitivity reported by patients will be recorded using both VAS and a verbal
      rating (VRS) scales. For VAS, the patient set her/his sensitivity level by pointing with a
      pen to the colored 10-cm scale and the distance from the border corresponding to absence of
      pain will be recorded. Tooth sensitivity will be also scored according to VRS, where 0 =
      none, 1 = mild, 2 = moderate, 3 = considerable, and 4 = severe.

      The maximum level of tooth sensitivity will be evaluated during the bleaching procedure,
      during the first 24 hours and the level of sensitivity at that time. VRS will define the
      presence (score different from 0) or absence of tooth sensitivity in all time assessments.
      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 and gender for each
      allocation sequence. Comparisons between the allocation sequences will be performed by the
      Mann-Whitney test (age) and Fisher's exact (gender).

      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.
    

Intervention name(s): Piroxicam-Beta-Cyclodextrin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): The patients will receive a single-dose of Piroxicam-Beta-Cyclodextrin (20 mg) thirty minutes before the bleaching procedure.; The patients will receive a single-dose of placebo with the same presentation of the experimental drug thirty minutes before the bleaching procedure.
Other intervention name(s): Cycladol (20mg) capsule; Starch capsule made to mimic Piroxicam-Beta-Cyclodextrin
Intervention MeSH terms: Piroxicam; Piroxicam-beta-cyclodextrin; Betadex
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Tooth Bleaching