title: The effectiveness of the biannual application of silver nitrate solution followed by sodium fluoride varnish in arresting early childhood caries in preschool children: study protocol for a randomised controlled trial.
abstract: BACKGROUND
  The application of 38 % silver diamine fluoride (SDF) has been shown to be effective in arresting early childhood caries (ECC). Since SDF is not available in certain countries, some dentists use adjunctive application of 25 % silver nitrate (AgNO3) and 5 % sodium fluoride (NaF) to arrest ECC. This randomised controlled trial will systematically compare the efficacy of a 25 % AgNO3 solution followed by 5 % NaF varnish with that of a 38 % SDF solution in arresting ECC when applied at half-yearly intervals over a 30-month period.
  
  
  METHODS
  This study is a randomised, double-blinded, non-inferiority clinical trial. The hypothesis tested is that adjunctive application of 25 % AgNO3 followed by 5 % NaF is at least not appreciably worse than a 38 % SDF in arresting ECC. Approximately 3100 kindergarten children aged 3-4 years will be screened and at least 1070 children with caries will be recruited. This sample size is sufficient for an appropriate statistical analysis (power at 90 % (β = 0.10) with a 2-sided type-I error of α = 0.05), allowing for an overall 20 % drop-out rate. The children will be randomly allocated into 2 groups to treat their caries over a 30-month period: Group A - biannual adjunctive application of a 25 % AgNO3 solution and a 5 % NaF varnish, and Group B - biannual adjunctive application of a 38 % SDF solution followed by a placebo varnish. Clinical examinations will be conducted at 6-month intervals. Primary outcome measured is the number of active caries surfaces which are arrested. Information on confounding factors such as oral hygiene habits will be collected through a parental questionnaire.
  
  
  CONCLUSIONS
  We expect that adjunctive application of 25 % AgNO3 solution and 5 % NaF varnish and of 38 % SDF solution can both effectively arrest ECC. Lower concentrations of silver and fluoride are contained in 25 % AgNO3 and 5 % NaF, respectively, than in 38 % SDF; therefore, AgNO3/NaF are more favourable for use in young children. Because its use for caries management is painless, simple, low-cost, and approved in many countries, AgNO3/NaF could be widely recommended and promoted as an alternative treatment to conventional invasive management of ECC.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT02019160 . Date of registration: 11 December 2013.
authors.affiliation: Faculty of Dentistry, University of Hong Kong, 34 Hospital Road, Hong Kong, SAR, China. chchu@hku.hk.
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Chu
authors.affiliation: Faculty of Dentistry, University of Hong Kong, 34 Hospital Road, Hong Kong, SAR, China. gao1204@hku.hk.
authors.forename: Sherry Shiqian
authors.initials: SS
authors.lastname: Gao
authors.affiliation: Faculty of Dentistry, University of Hong Kong, 34 Hospital Road, Hong Kong, SAR, China. skyli@hku.hk.
authors.forename: Samantha Ky
authors.initials: SK
authors.lastname: Li
authors.affiliation: Faculty of Dentistry, University of Hong Kong, 34 Hospital Road, Hong Kong, SAR, China. mcmwong@hku.hk.
authors.forename: May Cm
authors.initials: MC
authors.lastname: Wong
authors.affiliation: Faculty of Dentistry, University of Hong Kong, 34 Hospital Road, Hong Kong, SAR, China. hrdplcm@hku.hk.
authors.forename: Edward Cm
authors.initials: EC
authors.lastname: Lo
mesh_terms: D000287:Administration, Topical; D000367:Age Factors; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage* / Q000009:adverse effects; D002327:Cariostatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002675:Child, Preschool; D002985:Clinical Protocols; D019140:Dental Care for Children / Q000379:methods*; D003731:Dental Caries / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005460:Fluorides, Topical / Q000008:administration & dosage* / Q000009:adverse effects; D006723:Hong Kong; D006801:Humans; D008297:Male; D012107:Research Design; D012835:Silver Nitrate / Q000008:administration & dosage* / Q000009:adverse effects; D012969:Sodium Fluoride / Q000008:administration & dosage* / Q000009:adverse effects; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000891:Anti-Infective Agents, Local; D002327:Cariostatic Agents; D005460:Fluorides, Topical; C023807:sodium fluoride topical preparation; D012969:Sodium Fluoride; D012835:Silver Nitrate