BackgroundThis 18-month randomized clinical trial aimed to compare the effectiveness of two topical fluoride applications versus placebo control on preventing development of approximal caries in primary teeth.MethodsPreschool children were recruited if they had at least one initial approximal carious lesion at the distal surface of the canines, both approximal surfaces of the first molars, or the mesial surface of the second molars assessed from bitewing radiographs. The participants were randomly allocated into 3 intervention groups: Group 1 (placebo control), Group 2 (5% sodium fluoride [NaF] varnish), and Group 3 (38% silver diamine fluoride [SDF]). All agents were applied semiannually. Two calibrated examiners evaluated the caries development from bitewing radiographs. Caries development was recorded when the baseline sound surface or initial approximal carious lesion surface developed dentin caries (beyond the outer one-third of dentine) at the follow-up examination. The intention-to-treat approach was adopted. The Chi-square test was used to analyze the effectiveness of topical fluoride agents in preventing approximal caries development and the effect of other variables. The multi-level logistic regression analysis was performed to assess the relative effectiveness of topical fluoride agents in preventing approximal caries development at the 18-month follow-up.ResultsAt baseline, 190 participants with 2,685 sound or initial carries at the approximal surfaces were recruited. No differences in participant demographic backgrounds, oral health related habits, or caries experience were observed among the 3 groups (P> 0.05). After 18 months, 155 (82%) participants remained in the study. The rates of developing approximal caries in Groups 1, 2, and 3 were 24.1%, 17.1%, and 27.2%, respectively (P< 0.001,χ2test). After adjusting for confounding factors and clustering effect, the multilevel logistic regression analysis showed no differences in caries development rates between the 3 groups (P> 0.05). Tooth type and the extent of a carious lesion at baseline were the significant factors for caries development.ConclusionAt 18-month follow-up, after adjusting for confounding factors and clustering effect, there were no statistically significant differences in preventing of approximal caries development between the semiannual application of 5%NaF, 38%SDF, or placebo.Trial registrationThe study was registered in the Thai Clinical Trials Registry under the number TCTR20190315003 on 15/03/2019.