NCCL Direct Composite Restoration Performance With Self-Etch and Multimode Adhesives
Condition: Dental Adhesives/Restorations Performance
Study type: Interventional

Summary: 
      The purpose is to evaluate/compare clinical effectiveness of dual cure (DC) all-in-one
      Self-Etch (Futurabond® DC (FBDC)) adhesive and multimode/universal (Futurabond® U (FU) and
      Adhese® Universal (AU)) adhesives, with or without selective enamel etching, in non-carious
      cervical lesions (NCCL), during 24th months, using Word Dental Federation (FDI) and United
      States Public Health Services (USPHS) criteria.

      The null hypotheses are:

      H0 - Bonding to NCCLs with DC-SE and SE-Universal adhesives with SE strategies will result in
      similar (no significant differences) clinical (aesthetic, functional and biologic)
      behaviour/performance in a period of 24th month evaluation; H0 - Bonding to NCCLs with DC-SE
      and SE-Universal adhesives with SE strategies will result in similar restorations (aesthetic,
      functional and biologic) success rates over 24th month evaluation; H0 - Bonding to NCCLs with
      DC-SE and SE-Universal adhesives with SE strategies will result in similar restoration
      retention rates in a period of 24th month evaluation; H0 - Bonding to NCCLs DC-SE with enamel
      pre-etching and Universal adhesives with ER adhesive strategy will result in similar (no
      significant differences) clinical (aesthetic, functional and biologic) behaviour/performance
      in a period of 24thmonth evaluation; H0 - Bonding to NCCLs DC-SE with enamel pre-etching and
      Universal adhesives with ER adhesive strategy will result in similar restorations (aesthetic,
      functional and biologic) success rates over 24th month evaluation; H0 - Bonding to NCCLs
      DC-SE with enamel pre-etching and Universal adhesives with ER adhesive strategy will result
      in similar restoration retention rates in a period of 24th month evaluation; H0 - Bonding to
      NCCLs with FBDC or FU (DC adhesives) and AU (Light-curing adhesive) with SE or ER adhesive
      strategies will result in similar (no significant differences) clinical (aesthetic,
      functional and biologic) behaviour/performance in a period of 24th month evaluation; H0 -
      Bonding to NCCLs with FBDC or FU (DC adhesives) and AU (Light-curing adhesive) with SE or ER
      adhesive strategies will result in similar restorations (aesthetic, functional and biologic)
      success rates over 24th month evaluation; H0 - Bonding to NCCLs with FBDC or FU (DC
      adhesives) and AU (Light-curing adhesive) with SE or ER adhesive strategies will result in
      similar restoration retention rates in a period of 24th month evaluation; H0 - FDI or USPHS
      criteria evaluation outcomes not differ for the same data.
    

Detailed description: 
      2.1- DESIGN The trial design will follow the Consolidated Standards of Reporting Trials
      (CONSORT) statement (1, 2).

      Prospective, double blind clinical trial; randomized allocation of NCCL restorations by six
      adhesion treatment groups (6 arms: G1 to G6) for examination of restorations performance.
      Study will take place in University Fernando Pessoa - Faculty of Health Sciences (UFP-FHS),
      Dental Medicine School Clinic. Participants recruitment estimated between November 2015 and
      April 2016.

      The study is scheduled to last 24th months. Baseline clinical observation will be done 30
      days after placement of adhesion restoration (First data), second observation at 12 months
      and last evaluation at 24 months (Data for Statistical analysis). Clinical trial may continue
      for similar assessment intervals, after 24th months evaluation. This situation requires new
      analysis according to clinical and economics conditions, at that time.

      2.2- POPULATION AND PARTICIPANT SELECTION

      All participants will be informed (Written and verbal information) about the trial conditions
      and purposes, but will not be aware of what tooth will received the adhesion treatment.
      Written informed consent, according to World Medical Association Declaration of Helsinki (3),
      will be obtained from all participants prior to starting the treatment. University Fernando
      Pessoa Ethics Committee review and approved the present protocol. This clinical trial is done
      according to the National Law 21/2014, of 16 April, and was analysed, approved and authorized
      by the National Competent Authorities:

        -  INFARMED, National Authority of Medicines and Health Products, IP (No.EC/011/2015;
           DPS/DM/450.10.053/2015/0314; Authorization at 4th August 2015)

        -  CEIC, National Ethics Committee for Clinical Research (No.20150305; Approved at 3th
           August 2015)

        -  CNPD, Portuguese Data Protection Authority (Authorization and registry 6430/2015 at 7
           July 2015; No.2536/2015).

      The decision to participate in this study is voluntary as well as the decision to refuse
      participation and decision of withdrawal of the same, at any time of the study course, are
      rights of the patient/participant. The operator (Dentist and Associate Professor of FHS-UFP)
      inform the patient/participant in all aspects related to the study. Refusal of patient
      participation, the participant's withdrawal and revocation of consent to participate in this
      study are rights of the patient/participant without any consequences or reprisal, and without
      interference in the relationship between users and teachers/ researchers / University,
      clinical entities.

      SAMPLE:

      Patients with clinical diagnosis of non-carious cervical lesion (NCCLs) located in
      pre-molars/molars (PM/M) teeth, with cavity dimensions defined in the study design.

      Two hundred and ten restorations will be performed, randomized in order to be allocated to
      six interventions (G1 to G6 arms), named as adhesion intervention groups.

      Within this trial, the number of teeth to be restored by participant will be between a
      minimum of 1 and a maximum of 6. The allocation of the study group (G1 to G6) to a particular
      tooth is random with the information available to the operator/principal investigator in
      sealed envelopes and previously prepared by the investigator-professional statistics. The
      allocation of the study group (G1, G2, G3, G4, G5, G6) to each tooth for a patient is
      performed randomly, but ensuring that the distribution of the groups is not repeated in the
      same patient. For this purpose, 210 envelopes with 35 sequences of 6 study groups will be
      organized by the statistical investigator (wherein each order of 6 groups is randomized).

      2.3- STUDY ADHESION ARMS Six groups (G1 to G6) of NCCL restorations will be randomized
      allocated according to adhesion strategy intervention.

      2.4- OPERATOR / EXAMINERS CALIBRATION Operator will do one restoration of each group in order
      to identify all steps involved in the application technique. This procedure will be done
      three times, with one week, interval. All restorations done by the same calibrated operator.
      Three experienced and calibrated dentists, not involved with the restoring procedures and
      therefore blinded to the group assignment, will perform the clinical evaluation. For training
      purposes, the examiners observed 10 photographs that were representative of each score for
      each criterion, in 10 cervical restorations (not included in this trial), each one, on two
      consecutive days. An intra-examiner and inter-examiner agreement will be calculated.

      Medical Devices Composition (According to Manufactures, Voco and Ivoclar Vivadent Safety data
      sheets for Adhesives and products):

        1. Futurabond® DC (Voco, Cuxhaven, Germany) Batch No.1532592:

           Liquid 1. Acidic adhesive monomer; BIS-GMA (5-10%), 2-HEMA (5-10%); pH-value 1.5 Liquid
           2. Ethanol (50-100%); Initiator (2.5-5%) Mixture. organic acids, BIS-GMA, 2-HEMA,
           TMPTMA, campherchinon, amines (DABE), BHT, catalysts, fluorides and ethanol.

        2. Futurabond® U (Voco, Cuxhaven, Germany) Batch No.1543141:

           Liquid 1. 2-hidroxyethyl methacrylate (2-HEMA) (25-50%); BIS-GMA (25-50%); HEDMA
           (10-25%); Acidic adhesive monomer (5-10%); Urethanedimethacrylate (UDMA) (5-10%);
           catalysts (≤ 2.5%); pH-value 2.3 Liquid 2. Ethanol (50-100%); Initiator (2.5-5%);
           catalysts (≤ 2.5%)

        3. Ivoclar Vivadent's Adhese® Universal (Ivoclar Vivadent AG, Liechtenstein) Batch
           No.U35131:

           Composition/information on ingredients; mixture of substances Liquid: 2-hydroxyethyl
           methacrylate (20-<25%); bisphenol A diglycidyl ether dimethacrylate (20-<25%); ethanol
           (10-<25%); decamethylene dimethacrylate (3-<10%); Methacrylated phosphoric acid ester
           (3-<10%); campherquinone (1-<2.5%); 2-dimethylaminoethyl methacrylate (1-<2.5%);
           2,6-di-tert-butyl-p-cresol (0.1-<0.3%). (MDP-Methacryloyloxydecyl dihydrogen phosphate;
           MCAP- Methecrylated carboxylic acid polymer; HEMA-Hydroxyethil methacrylate; Bis-GMA_
           Bisphenol A glycidyl methacrylate; D3MA- Decandiol dimethacrylate); pH-value 2.5-3.0.

        4. Vococid® (Voco, Cuxhaven, Germany) Batch No.152135: 35% orthophosphoric acid; 2.5- DATA
           REGISTRY/PROTECTION AND RESTORATIONS PROCEDURES Only in the registration database (with
           access to the principal investigator and other team members, with the exception of the
           statistical investigator for the purposes of observational clinical records) there
           should be registration/membership of this key with the code-process of patients. The
           database in question will be lodged in own servers with restricted access levels and
           well identified. The servers that lodge the photos/ records and the database belong to
           Dental School Clinic of Faculty of Health Sciences - UFP and are located in data centre
           with fully controlled access. This mechanism ensures the concealment of identity of the
           user in records file, having access to them only the investigator and research team
           (except investigator of statistics). This mechanism fulfilled the recommendation and
           Authorisation of CNPD, Portuguese Data Protection Authority (Authorization and registry
           6430/2015 at 7 July 2015; Case 2536/2015).

      Appointment and restorative procedures, in accordance with the following steps:

      One week, before the Restorative procedure (1st appointment): Inform the patient
      (Written/Verbal); Patient signature of informed consent; Fulfilment of the project clinical
      file (patient identification, general clinical summary, oral clinic examination, oral hygiene
      state); Dental prophylaxis with fluoride toothpaste and water with a nylon brush. Vitality
      tests (cold and hot) executed with spray Endo cool (ethyl chloride) and warm instrument;
      Pre-operative sensitivity evaluation by applying air for 10 seconds from a dental syringe
      placed 2 cm from the tooth surface (4); NCCLs cavities will be evaluated according to the
      degree (1, 2, 3, 4) of sclerotic dentin (5), cavity dimensions (H-height, W-width, and
      D-depth) in millimetres (mm) and geometry (evaluated by profile photograph, as Angles Acute
      (A), Severe (S), Obtuse (O) (4); 1st Appointment-Intervention: Initial intra-oral/cavity
      surface and tooth digital photography; Teeth anaesthesia with 3% mepivacaine (Scandinibsa,
      Sintra Business Park, Portugal); Operatory field isolation with cotton rolls and retraction
      floss (Ultradent). All cavities cleaned with pumice and water in a rubber cup, followed by
      rinsing and drying. Selection composite colour by shade guide; Adhesive interventions
      according to G1 to G6 arms assignment. Adhesive systems will be used as SingleDose mode.
      Composite restorations (AdmiraFusion Universal nano-hybrid composite) with incremental
      filling technique (two increments maximum), light-cured (LED Unit) with an intensity of
      1000mW/cm2, during 40 seconds. Restorations will be finished immediately with diamond disks
      (OptiDisc® medium 40μm; Kerr) and burns. Polishing performed with diamond-impregnated
      silicone polishers (Dimanto, Voco, CuxHaven) during 10 seconds. Intra-oral digital
      photography of the restoration.

      2.6- CLINICAL FOLLOW-UP Baseline (30 days after restoration), 12th (NCCLs observation) and
      24th months (for statistical analysis) Appointments

      1 - Intra-oral digital photography of the NCCL restoration; 2- Post-operative sensitivity
      evaluation by applying air for 10 seconds from a dental syringe placed 2 cm from the tooth
      surface (4); 3 - Direct evaluation by 3 calibrated examiners according to FDI (6, 7) and
      USPHS (8); 4- Data register Study variable definition - Clinical/direct observation and
      performance evaluation acceptance by means of FDI and USPHS criteria.

      2.7- DATA BASE AND STATISTICAL ANALISYS Data statistical analysis and description according
      to aims of this trial; Specific program for statistical data analysis (IBM(c) SPSS(c)
      Statistics vs. 23 or later) will be used. Differences will be considered to be significant at
      p<0.05.

      2.8- OBSERVATIONS REGARDING SAMPLE CALCULATION Was assumed that the minimum number of bonded
      restorations to be held in each of the six arms (G1 to G6) is 35 (210 restorations). The
      researchers did not have detailed information that allows the estimation of the sample size
      based on power analysis (the effect of the expected difference to the end of the time
      considered for the study). Thus, using rules of thumb usually considered in research
      situations where there is no prior information concerning the performance evaluation of these
      class IIa medical devices available on the market. In this case, considering that it intends
      to make a prospective longitudinal study, to determine factors associated with failure rate
      and reduced clinical performance (effect) criteria of the restorations, and to detect effects
      depends the number of events (failure, for example, or other event that is to be considered
      in the defined evaluation criteria) and not the number of participants, the thumb rules
      stipulate a minimum of 10 cases by group. Moreover, when considering an "simple" analysis
      comparison using a McNemar test (repeated measures) in six groups would be necessary in
      total, including at least 80 cases (to restore teeth) in the sample. When considering at
      least 35 restorations by group, researchers are greatly increasing the minimum number
      stipulated in any of the aforementioned techniques. In addition, clinical studies previously
      performed on this issue (between 2004 and 2012) relative to the post-market clinical
      evaluation performance of class IIa medical devices, in the context of restorative dentistry
      field, has enabled to measure a minimum of 30 restorations as viable for determining events
      in a short/medium-term as the clinical performance evaluation of a similar nature of medical
      devices.

      2.9- GOOD CLINICAL PRACTICE FOR CLINICAL RESEARCH Reporting mechanism of possible adverse
      incident during the investigation will be held according to Medical Devices (MD) commercially
      available in the market, so it interprets and assumes the issue as applicable to assumptions
      in the Portuguese National Law (Article 22) 21/2014, of 16 April, calling up a mechanism for
      reporting any incidents inherent to medical devices or resulting from the use of medical
      devices. In this way, and considering the type of intervention to carry out in this research
      (restoration of very small extension of NCCL with dental adhesives), the medical devices
      (Adhesive systems) are not described in the literature and not known records for the
      occurrence of undesirable incidents, with interpretative effects as Serious or Unexpected
      "adverse incidents". However, and according to good clinical practice for clinical research,
      the reporting mechanism of Serious or Unexpected incidents (protocol version FHS-UFP-FFP-2014
      April-19.07.2015) for this research are approved by CEIC (National Ethics Committee for
      Clinical Research (No.20150305; Approved at 3th August 2015).

      Sponsor reports annually to CEIC and INFARMED a list of all suspected serious adverse events,
      during this period as well as a report on the safety of participants, if applicable. Under
      the study protocol (Version FCS-UFP-FFP-2014 April-19.07.2015), all the possible non-serious
      adverse events such as, clinical signs or symptoms associated with loss of aesthetic,
      functional and biological performance of restorations and situations described in the
      instructions, labelling and safety data sheets of medical devices or even, without incident
      and security maintenance data of the participants the sponsor notifies the CEIC and INFARMED,
      only by the final evaluation of this study (two years of clinical performance), as set forth
      in article 24th of Law 21/2014 of 16 April, which will include a report of suspicious
      occurrences and safety records and, if applicable, in the clinical trial in the period
      Evaluation of two years.
    

Intervention name(s): G1-Control: Futurabond®DC-SE (FBDC_SE); G2-Control: Futurabond®DC_SE_EE; G3: Futurabond® U - ER (FBU_ER); G4: Futurabond® U - SE (FBU_SE); G5: Adhese® Universal - ER (ADU_ER); G6: Adhese® Universal - SE (ADU_SE)
Intervention type(s): Device; Device; Device; Device; Device; Device
Intervention description(s): Futurabond®DC (FBDC) adhesive by self-etch (SE) mode bonding in NCCls restorations, was randomly assigned to premolar or molar teeth ensuring that this adhesive/mode is only apllied once in each participant.; Futurabond®DC adhesive by self-etch mode with selective enamel etching (FBDC-SE-EE) bonding in NCCls restorations, was randomly assigned to premolar or molar teeth ensuring that this adhesive/mode is only apllied once in each participant.; FuturabondU® (FBU) adhesive by etch-and-rinse (ER) mode, bonding in NCCls restorations, was randomly assigned to premolar or molar teeth ensuring that this adhesive/mode is only apllied once in each participant.; FuturabondU® (FBU) adhesive by self-etch (SE) mode, bonding in NCCls restorations, was randomly assigned to premolar or molar teeth ensuring that this adhesive/mode is only apllied once in each participant.; Adhese®Universal (ADU) adhesive by etch-and-rinse (ER) mode, bonding in NCCls restorations, was randomly assigned to premolar or molar teeth ensuring that this adhesive/mode is only apllied once in each participant.; Adhese®Universal (ADU) adhesive by self-etch (SE) mode, bonding in NCCls restorations, was randomly assigned to premolar or molar teeth ensuring that this adhesive/mode is only apllied once in each participant.
Other intervention name(s): Futurabond®DC_Self-etch mode (FBDC_SE); Futurabond®DC_selective Enamel Etching (FBDC_SE_EE); Futurabond® U_Etch-and-Rinse mode (FBU_ER); Futurabond® U - Self-Etch mode (FBU_SE); Adhese® Universal - Etch-and-rinse mode (ADU_ER); Adhese® Universal - Self-Etch mode (ADU_SE)
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Other
Keywords: composite resins; dental restoration; adhesives; non-carious cervical lesions; clinical effectiveness; Adhese universal; Futurabond U; Futurabond DC; self-etch; multimode/universal; clinical trial